U.S. patent application number 12/363016 was filed with the patent office on 2009-08-13 for mir-150 for the treatment of blood disorders.
This patent application is currently assigned to THE GENERAL HOSPITAL CORPORATION. Invention is credited to Benjamin Ebert, Todd Golub, Shangqin Guo, Jun Lu, David Scadden.
Application Number | 20090202493 12/363016 |
Document ID | / |
Family ID | 40939053 |
Filed Date | 2009-08-13 |
United States Patent
Application |
20090202493 |
Kind Code |
A1 |
Lu; Jun ; et al. |
August 13, 2009 |
MIR-150 FOR THE TREATMENT OF BLOOD DISORDERS
Abstract
The invention provides methods of treating certain blood related
disorders, in particular, thrombocytopenia and anemia comprising
increasing miR-150 expression or inhibiting miR-150 in progenitor
cells respectively.
Inventors: |
Lu; Jun; (North Haven,
CT) ; Guo; Shangqin; (North Haven, CT) ;
Ebert; Benjamin; (Brookline, MA) ; Scadden;
David; (Weston, MA) ; Golub; Todd; (Newton,
MA) |
Correspondence
Address: |
DAVID S. RESNICK
NIXON PEABODY LLP, 100 SUMMER STREET
BOSTON
MA
02110-2131
US
|
Assignee: |
THE GENERAL HOSPITAL
CORPORATION
Boston
MA
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Cambridge
MA
DANA-FARBER CANCER INSTITUTE, INC.
Boston
MA
|
Family ID: |
40939053 |
Appl. No.: |
12/363016 |
Filed: |
January 30, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61062931 |
Jan 30, 2008 |
|
|
|
61086556 |
Aug 6, 2008 |
|
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Current U.S.
Class: |
424/93.2 ;
514/44R |
Current CPC
Class: |
A61P 7/02 20180101; C12N
2310/321 20130101; C12N 2310/346 20130101; C12N 2310/113 20130101;
C12N 2310/341 20130101; A61P 7/06 20180101; A61K 31/7105 20130101;
C12N 2330/10 20130101; C12N 2310/141 20130101; C12N 2310/3515
20130101; C12N 2310/111 20130101; C12N 2310/315 20130101; C12N
15/113 20130101; C12N 2310/321 20130101; C12N 2310/3521
20130101 |
Class at
Publication: |
424/93.2 ;
514/44.R |
International
Class: |
A61K 48/00 20060101
A61K048/00; A61P 7/06 20060101 A61P007/06; A61P 7/02 20060101
A61P007/02 |
Goverment Interests
GOVERNMENT SUPPORT
[0002] This invention was made with Government support under No.
219335 awarded by the National Institute of Health. The Government
has certain rights in the invention.
Claims
1. A method of treating thrombocytopenia in a host in need thereof,
the method comprising administering an effective amount of an agent
that increases miR-150 expression in a cell to a host.
2. The method of claim 1, wherein the cell is a progenitor
cell.
3. The method of claim 2, wherein the progenitor cell is a
hematopoietic progenitor cell.
4. The method of claim 1, wherein the agent is a vector comprising
a nucleic acid sequence that is at least 90% identical to SEQ. ID.
No. 1.
5. The method of claim 4, wherein the vector is a virus.
6. The method of claim 1, wherein the agent is a nucleic acid
sequence that is at least 90% identical to SEQ. ID. No. 1.
7. A method of treating thrombocytopenia in a host in need thereof,
the method comprising: a. obtaining a sample of hematopoietic
progenitor cells from said host; b. contacting the hematopoietic
progenitor cells with a vector comprising a nucleic acid sequence
that is at least 90% identical to SEQ. ID. No. 1; and c.
introducing the cell from step b into the host.
8. A method of treating anemia in a host in need thereof, the
method comprising administering an effective amount of an agent
that inhibits miR-150 in a cell to a host.
9. The method of claim 8, wherein the cell is a progenitor
cell.
10. The method of claim 9, wherein the progenitor cell is a
hematopoietic progenitor cell.
11. The method of claim 8, wherein the agent is a vector comprising
a nucleic acid sequence that is at least 90% identical to SEQ. ID.
No. 3.
12. The method of claim 8, wherein the agent is an antagomir of
miR-150, an anti-miR-150 oligonucleotide, an antisense
oligonucleotide to miR-150 or a locked nucleic acid that anneals to
miR-150.
13. A method of claim 11, wherein the vector is a virus.
14. A method of treating anemia in a host in need thereof, the
method comprising: a. obtaining a sample of hematopoietic
progenitor cells from said host; b. contacting the hematopoietic
progenitor cells with a vector comprising a nucleic acid sequence
that is at least 90% identical to SEQ. ID. No. 3; and c.
introducing the cell from step b into the same host.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application claims benefit under 35 U.S.C. .sctn.
119(e) of the U.S. provisional applications No. 61/062,931 filed on
Jan. 30, 2008, and No. 61/086,556 filed on Aug. 6, 2008, the
contents of which are incorporated herein by reference in their
entirety.
BACKGROUND OF INVENTION
[0003] Blood disorders such as thrombocytopenia and anemia affect a
significant population, with anemia being the most common disorder
of the two. At least 50% of new patients admitted to a hospital's
intensive care unit will develop thrombocytopenia during their
stay. The development of thrombocytopenia correlates with
mortality, longer duration of mechanical ventilation, and an
increased need for blood product transfusion.
[0004] Anemia occurs when the level of healthy red blood cells
(RBCs) in the body becomes too low. RBCs contain hemoglobin, which
carries oxygen to the body's tissues. Thus, low levels of healthy
RBCs can cause a variety of complications, including fatigue and
stress on bodily organs. More than 3 million people in the United
States have anemia. Women and people with chronic diseases are at
the greatest risk for anemia. A person presents with anemia when
the body loses too much blood (such as with heavy periods, certain
diseases, and trauma); or the body has problems making red blood
cells; or red blood cells break down or die faster than the body
can replace them with new ones; or more than one of these problems
happen at the same time.
[0005] Aplastic anemia occurs when the bone marrow cannot make
enough RBCs. This can be due to a viral infection, or exposure to
certain toxic chemicals, radiation, or medications (such as
antibiotics, antiseizure drugs, or cancer treatments). Some
childhood cancers can also cause aplastic anemia, as can certain
chronic diseases that affect the ability of the bone marrow to make
blood cells. Vitamin B12 and iron deficiencies also contribute to
anemia.
[0006] Thrombocytopenia is a deficiency of platelets
(thrombocytes). The blood usually contains about 140,000 to 440,000
platelets per microliter. Bleeding can occur with relatively minor
trauma when the platelet count falls below about 50,000 platelets
per microliter of blood. The most serious risk of bleeding,
however, generally does not occur until the platelet count falls
below 10,000 to 20,000 platelets per microliter. At these very low
levels, bleeding may occur without any injury.
[0007] Abnormal reductions in the number of platelets are caused
when abnormalities occur in any of the following three processes:
decreased platelet production by the bone marrow; increased
trapping of platelets by the spleen; or a more rapid than normal
destruction of platelets. Persons with this condition easily bruise
and can have episodes of excess bleeding (a hemorrhage).
[0008] Many diseases can cause thrombocytopenia. Thrombocytopenia
can occur when the bone marrow does not produce enough platelets,
as happens in leukemia, lymphoma and some anemias-aplastic,
megaloblastic, vitamin B12 deficiency, and folic acid deficiency.
Excessive alcohol consumption can also imped platelet production.
Infection with the human immunodeficiency virus (HIV), the virus
that causes AIDS, often results in thrombocytopenia. Platelets can
become entrapped in an enlarged spleen, as happens in myelofibrosis
and Gaucher's disease, reducing the number of platelets in the
bloodstream. Massive blood transfusions can dilute the
concentration of platelets in the blood. Finally, the body may use
or destroy too many platelets, as occurs in many disorders, three
of the most notable being idiopathic thrombocytopenic purpura,
thrombotic thrombocytopenic purpura, and hemolytic-uremic
syndrome.
[0009] Currently, the treatment options for anemia and
thrombocytopenia are directed at the immediate increase of
circulating RBC and platelet respectively, followed by identifying
the underlying causes. Alternative treatment methods aimed at
boosting the innate production of RBCs and platelets, for example,
the use of erythropoietin and thrombopoietin to stimulate the bone
marrow to produce more red blood cells, are still needed and will
be useful in complementing existing treatments for anemia and
thrombocytopenia.
SUMMARY OF THE INVENTION
[0010] Embodiments of the invention provide methods of treating
certain blood related disorders, in particular, thrombocytopenia
and anemia. Thrombocytopenia is a condition where there is low
platelet count in the blood. Anemia is a condition where there is a
low number of red blood cells (RBC) in the blood. Embodiments of
the inventions are based on the discovery that miR-150 is involved
in the differentiation of megakaryocyte-erythrocyte progenitor
cells (MEPs) from the bone marrow. Overexpression of miR-150 can
shift more MEPs toward megakaryocyte differentiation and also block
erythrocyte maturation. In contrast, a lower level of miR-150
expression shift more MEPs towards erythrocyte differentiation.
Accordingly, embodied in the invention is a method of treating
thrombocytopenia in a host in need thereof, the method comprising
administering to a host an effective amount of an agent that
increases miR-150 expression in a cell.
[0011] The cell being administered an effective amount of an agent
that increases miR-150 expression is a progenitor cell, preferably,
a hematopoietic progenitor cell. The increase in miR-150 expression
promotes megakaryocyte differentiation from the hematopoietic
progenitor cell and consequently more platelets are produced.
[0012] In one embodiment, the agent that increases miR-150
expression in a cell comprises a vector comprising a nucleic acid
sequence that is at least 90% identical to SEQ. ID. No. 1. In other
embodiments, the nucleic acid is at least 92%, at least 93% at
least 94%, at least 95%, at least 96%, at least 97%, at least 98%,
at least 99%, and all the intermediate percentages between 90% and
100%, identical to SEQ. ID. No. 1. The differences from SEQ. ID.
No. 1 should be such that the overall hairpin structure of the
pri-miR-150 is maintained. The agent serves to increase the basal
level of miR-150 in hematopoietic progenitor cells. The vector can
be a virus or a non-virus.
[0013] In another embodiment, the agent that increases miR-150
expression in a cell comprises a nucleic acid sequence that is at
least 90% identical to SEQ. ID. No. 1. In other embodiments, the
nucleic acid is at least 92%, at least 94%, at least 95%, at least
97%, at least 99%, and all the intermediate percentages between 90%
and 100%, identical to SEQ. ID. No. 1. The differences from SEQ.
ID. No. 1 should be such that the overall hairpin structure of the
pri-miR-150 is maintained.
[0014] Embodied herein is a method of treating thrombocytopenia in
a host in need thereof, the method comprising: (a) obtaining a
sample of hematopoietic progenitor cells from the host; (b)
contacting the hematopoietic progenitor cells with a vector
comprising a nucleic acid sequence that is at least 90% identical
to SEQ. ID. No. 1; and (c) introducing the cell from step b into
the host.
[0015] Also embodied herein is a method of treating anemia in a
host in need thereof, the method comprising administering to a host
an effective amount of an agent that inhibits miR-150 in a
cell.
[0016] The cell being administered an effective amount of an agent
that inhibits miR-150 expression is a progenitor cell, preferably,
a hematopoietic progenitor cell. By inhibiting miR-150 expression
in the cells, the repression associated with the miR-150 is
relieved and erythrocyte differentiation from the progenitor cells
is promoted.
[0017] In one embodiment, the agent comprises a vector comprising a
nucleic acid sequence that is at least 90% identical to SEQ. ID.
No. 3. In another embodiment, the agent is an antagomir of miR-150,
an anti-miR-150 oligonucleotide, an antisense oligonucleotide to
miR-150, a locked nucleic acid that anneals to miR-150, or a double
strand RNA. Nucleic acid sequences similar to SEQ. ID. No. 3,
antagomir of miR-150, an anti-miR-150 oligonucleotide, an antisense
oligonucleotide to miR-150, a locked nucleic acid that anneals to
miR-150, or a double strand RNA all complementary base-pair with
miR-150, although not necessarily perfectly, and can thus inhibit
miR-150 from complexing with the miRISC. The vector comprising a
nucleic acid sequence can be virus or a non-virus.
[0018] Embodied herein is a method of treating anemia in a host in
need thereof, the method comprising: (a) obtaining a sample of
hematopoietic progenitor cells from said host; (b) contacting the
hematopoietic progenitor cells with a vector comprising a nucleic
acid sequence that is at least 90% identical to SEQ. ID. No. 3; and
(c) introducing the cell from step b into the same host.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] FIG. 1A shows the schematic of a novel, sensitive and
high-throughput miRNA labeling methodology for expression
profiling. RT: reverse transcription; Bi: biotin; arrows:
primers.
[0020] FIG. 1B shows a heatmap on log 2-transformed data, with
black color indicating higher expression and light grey for lower
expression. Data reflect the median expression of miRNAs within
corresponding populations. Arrows point to miRNAs mentioned in
text. Multiple harvests of MEP (n=8), MEGA1 (n=4), MEGA2 (n=6),
ERY1 (n=4), ERY2 (n=3), and ERY3 (n=2) populations were purified
from human umbilical cord blood cells (23) and profiled for miRNA
expression.
[0021] FIG. 1C shows the median expression of miR-150 was plotted
for each population, with the oval area proportional to the
expression level.
[0022] FIG. 1D shows miR-150 expression measured using quantitative
RT-PCR on multiple harvests of MEP (n=3), MEGA1 (n=4), MEGA2 (n=3),
ERY1 (n=3), ERY2 (n=3) and ERY3 (n=3) populations. The .DELTA.Ct
values (Ct (threshold cycle) of 18S minus Ct of miR-150) are shown
for all samples. Note that .DELTA.Ct reflects log scale of
expression. Samples indicated with black dots were also used in
miRNA profiling in FIGS. 1B and 1C, whereas those with open circles
were additional samples.
[0023] FIG. 2A shows representative flow cytometry plots of the
differentiation lineage of CD34+ hematopoietic progenitors cells
transduced with constructs expressing a control hairpin (shLuc),
miR-150, a mutant miR-150 or miR-15b-16-2. Plots represents lineage
markers CD41 (megakaryocytic) and GlyA (erythroid).
[0024] FIG. 2B shows the histograms of the data obtained for FIG.
2A. Error bars reflect standard deviation. n=3
[0025] FIG. 2C shows the percentage of bone marrow GFP+ or GFP-
megakaryocytes (CD41+Ter119-)-J) in mice transduced with either
miR-150 and a GFP marker or with control retroviral vector and
analyzed 5 to 8 weeks post-transplantation. Each dot represents
data from one recipient mouse. n=7.
[0026] FIG. 2D shows the percentage of bone marrow GFP+ or GFP-
erythrocyte (CD41-Ter119+) in mice transduced with either miR-150
and a GFP marker or with control retroviral vector and analyzed 5
to 8 weeks post-transplantation. Each dot represents data from one
recipient mouse. n=7.
[0027] FIG. 2E shows representative flow cytometry plots on bone
marrow cells with megakaryocytic (CD41) and erythroid (Ter119)
markers from data of FIGS. 2C and 2D.
[0028] FIG. 2F shows the PF4 expression of recipient bone marrow
cells that are GFP+ and GFP-. Each pair of bars represents data
from one recipient mouse.
[0029] FIG. 2G shows the ratio of GFP+ platelet percentage to the
percentage of GFP+ bone marrow cells in the peripheral blood of
recipient animals 7-week post-transplantation. T was plotted to
reflect the thrombocytogenic potential of bone marrow cells.
n=5.
[0030] FIG. 2H show the representative flow cytometry plots of bone
marrow cells assayed with CD71 and Ter119. The gates R1 to R4
represent immature to mature erythrocytes.
[0031] FIG. 2I shows a ratio between GFP+ and GFP- population
within the same recipient mouse based upon the percentage of R1
population among all erythrocytes (sum of R1 to R4), n=7.
P<0.002.
[0032] FIG. 2J shows a ratio between GFP+ and GFP- population
within the same recipient mouse based on data for R4 population.
P<2.times.10-4.
[0033] FIG. 3A shows the megakaryocyte colony forming units
(CFU-Mks) formed from GFP+ and GFP- populations of bone marrow
cells isolated from mice transduced with miR-150 retroviral vector
or vector control. CFU-Mks were quantitated from 100,000 sorted
cells. n=4.
[0034] FIG. 3B shows the effects of solvent (PBS), antagomir
against miR-150 (anti-150) or a scrambled antagomir on the
differentiation of CFU-Mk from MEP cells sorted from wild-type
C57BL/6J mice. 4000 cells were analyzed per assay. n=4.
[0035] FIG. 3C shows the effects of solvent (PBS), antagomir
against miR-150 (anti-150) or a scrambled antagomir on the
differentiation of CFU-Mk from Lin-Kit+Sca+(LKS) stem cells. 1000
cells were analyzed per assay. n=4.
[0036] FIG. 3D shows the miR-150 expression in mice were treated
with phenylhydrazine to induce anemia, or in mice were treated with
PBS (mock). miR-150 expression was assayed by qRT-PCR in lineage
negative cells purified from bone marrow. n=3. Error bars represent
standard deviation.
[0037] FIG. 4A shows the Western blot analysis for MYB and
beta-Tubulin expressed in K562 cells transduced with constructs
expressing GFP, mutant miR-150 or miR-150.
[0038] FIG. 4B shows the design of luciferase reporters for human
MYB 3' UTR, with grey vertical bar indicating wild-type (wt) sites
and black indicating mutant (mut) sites. The mutant miRNA site and
mutant 3'UTR sites are complementary.
[0039] FIG. 4C shows a normalized plot of luciferase activities in
293T cells transduced with constructs expressing GFP, mutant
miR-150 or miR-150. Error bars represent standard deviation.
n=8.
[0040] FIG. 4D shows the histograms of the differentiation lineages
of cells transduced with miR-150 and MYB expression constructs and
their corresponding vector controls (shLuc, Vector). The lineage
markers are CD41 (megakaryocytic) and GlyA (erythroid). n=3. Error
bars reflect standard deviation. *P=0.04.
[0041] FIG. 4E shows the representative flow cytometry plots of the
differentiation lineages in FIG. 4D. Plots represents lineage
markers CD41 (megakaryocytic) and GlyA (erythroid).
[0042] FIG. 5A shows the reproducibility performance of the plate
capture method of miRNA labeling.
[0043] FIG. 5B shows the comparison of methods. miRNA expression
profiling was performed on the same MCF-7 and 293T total RNA using
either the plate capture method, or the previously reported method
involving multiple denaturing acrylamide gel purification of small
RNAs ("gel purification method").
[0044] FIG. 6A shows the expression of miR-150 in FACS-sorted
umbilical cord blood populations. Expression is measured by
quantitative RT-PCR analysis as in FIG. 1D were plotted in an oval
plot with the oval area proportional to the median value of
2.sup..DELTA.Ct for each of the populations.
[0045] FIG. 6B shows the histogram of miR-150 expression in
CD41+CD61+ and CD71+GlyA+ cells FACS-sorted from the bone marrow of
a healthy adult human donor. miR-150 expression was measured using
quantitative RT-PCR. 2.sup..DELTA.Ct values are shown. Error bars
represent standard deviation of measurement.
[0046] FIG. 7 shows the evolutionary conservation of mature miR-150
sequences of across multiple species. Sequence data were from
miRBASE. Big and bold letters indicate non-conserved bases.
[0047] FIG. 8 shows the miR-150 expression in cultured human CD34+
bone marrow cells transduced with a control vector (shLuc, n=3) or
a m-iR150 construct (n=3), and in multiple harvests of MEP, ERY1,
ERY2, ERY3, MEGA1 and MEGA2 populations (as described in FIG. 1D).
Threshold cycle values were normalized against 1 8S ribosomal RNA
levels. .DELTA.Ct values are plotted
[0048] FIG. 9 shows a schematic model for murine bone marrow
transplantation.
[0049] FIG. 10A shows the gated forward and side scattering flow
cytometry analysis of bone marrow cells from wild-type mouse and
recipient mice 5-8 weeks after transplantation with vector control
or miR-150 vector. GFP gating was determined on cells from
wild-type animal.
[0050] FIG. 10B shows the GFP gated flow cytometry analysis of bone
marrow cells from recipient mice 5-8 weeks after transplantation
with vector control.
[0051] FIG. 10C shows the GFP gated flow cytometry analysis of bone
marrow cells from recipient mice 5-8 weeks after transplantation
with miR-150 vector.
[0052] FIG. 10D shows the GFP gated flow cytometry analysis of bone
marrow cells from wild-type mouse.
[0053] FIG. 11A shows the gated sensitized forward and side
scattering flow cytometry analysis of platelets in peripheral blood
of wild-type mouse and from recipients 7 weeks after
transplantation with vector control or miR-150 vector. Peripheral
blood cells were stained with CD41 antibody.
[0054] FIG. 11B shows the GFP and CD41 flow cytometry analysis of
platelets in peripheral blood from recipients 7 weeks after
transplantation with vector control.
[0055] FIG. 11C shows the GFP and CD41 flow cytometry analysis of
platelets in peripheral blood from recipients 7 weeks after
transplantation with miR-150 vector.
[0056] FIG. 11D shows the GFP and CD41 flow cytometry analysis of
platelets in peripheral blood from wild-type mouse.
[0057] FIG. 12A shows the absolute cell numbers of GFP+
erythrocytes in the bone marrow of vector control or miR-150
recipient mice. Data reflect cell numbers from two legs of each
mouse. Cell number was calculated based on total bone marrow cell
yield, GFP status and megakaryocyte and erythrocyte percentage as
determined by CD41 and Ter 119 staining.
[0058] FIG. 12B shows the absolute cell numbers of GFP+
megakaryocytes in the bone marrow of vector control or miR-150
recipient mice.
[0059] FIG. 12C shows the absolute cell numbers of GFP-
erythrocytes in the bone marrow of vector control or miR-150
recipient mice.
[0060] FIG. 12D shows the absolute cell numbers of GFP-
megakaryocytes in the bone marrow of vector control or miR-150
recipient mice.
[0061] FIG. 13 shows that miR-150 decreases erythroid colony
formation.
[0062] FIG. 14 shows that antagomir-150 knocks down miR-150
expression.
[0063] FIG. 15 shows the formation of megakaryocyte colony in the
presence of antagomir-150. Brown color reflects
megakaryocyte-specific acetylchol inesterase activity.
[0064] FIG. 16A shows the MYB expression as measured using
quantitative RT-PCR on multiple harvests of MEP (n=3), MEGA1 (n=4),
MEGA2 (n=3), ERY1 (n=3), ERY2 (n=3) and ERY3 (n=3) populations. The
.DELTA.Ct values (Ct of 18S minus Ct of MYB) are shown for all
samples. Samples with black dots were used in miRNA profiling in
FIGS. 1B and 1C, whereas those with open circles are additional
samples.
[0065] FIG. 16B shows the data plotted in an oval plot with the
oval area proportional to the median value of 2.sup..DELTA.Ct for
each of the MEP, MEGA1, MEGA2, ERY1, ERY2 and ERY3 populations.
[0066] FIG. 17A shows the human MYB 3'UTR sequence with four
putative miR-150 binding sites in boxes.
[0067] FIG. 17B shows the conservation of the four putative miR-150
targeting sites across several shown species. Conservation data
were obtained from UCSC genome browser.
[0068] FIG. 18A shows the knockdown efficiency of two independent
shRNAs against MYB expression in MYB-expressing K562 cells. MYB
expression was measured by quantitative RT-PCR. The values of
2.sup..DELTA.Ct are shown.
[0069] FIG. 18B shows the percentage of differentiated
megakaryocytes (CD41+GlyA-) from CD34+ human adult bone marrow
cells transduced with control vector (shLuc), miR-150 or shRNAs
against MYB in an in vitro culture. n=3. Error bars represent
standard deviation.
DETAILED DESCRIPTION OF THE INVENTION
Definitions of Terms
[0070] As used herein, the term "comprising" means that other
elements can also be present in addition to the defined elements
presented. The use of "comprising" indicates inclusion rather than
limitation.
[0071] The term "consisting of" refers to compositions, methods,
and respective components thereof as described herein, which are
exclusive of any element not recited in that description of the
embodiment.
[0072] As used herein the term "consisting essentially of" refers
to those elements required for a given embodiment. The term permits
the presence of elements that do not materially affect the basic
and novel or functional characteristic(s) of that embodiment of the
invention.
[0073] As used herein, the term "therapeutically effective amount"
refers to an amount of an agent that is sufficient to effect a
therapeutically significant increase in the circulating platelet
count in a host diagnosed with thrombocytopenia to at least above
1.6.times.10.sup.5 platelets/mm.sup.3 or an amount of an agent that
is sufficient to effect a therapeutically significant increase in
the circulating RBC count in a host diagnosed with anemia to at
least above 4.0.times.10.sup.12 red cells/L in adults and
4.6.times.10.sup.12 red cells/L in children.
[0074] As used herein, the term "treating thrombocytopenia" refers
to a means of increasing the number of circulating platelets in a
host who has low platelet count, less than about 1.6.times.10.sup.5
platelets/mm.sup.3.
[0075] As used herein, the term "agent" refers to a nucleic acid
sequence or a vector. The nucleic acid sequence can have
modifications such as 2'O-methylation and 3' end cholesterol found
in antagomirs and locked nucleic acid oligonucleotides.
[0076] As used herein, the term "complementary base pair" refers to
A:T and G:C in DNA and A:U in RNA. Most DNA consists of sequences
of nucleotide only four nitrogenous bases: base or base adenine
(A), thymine (T), guanine (G), and cytosine (C). Together these
bases form the genetic alphabet, and long ordered sequences of them
contain, in coded form, much of the information present in genes.
Most RNA also consists of sequences of only four bases. However, in
RNA, thymine is replaced by uridine (U).
[0077] As used herein, the term "nucleic acid sequence" refers to
any molecule, preferably a polymeric molecule, incorporating units
of ribonucleic acid, deoxyribonucleic acid or an analog thereof.
The nucleic acid can be either single-stranded or double-stranded.
A single-stranded nucleic acid can be one strand nucleic acid of a
denatured double-stranded DNA. Alternatively, it can be a
single-stranded nucleic acid not derived from any double-stranded
DNA. In one aspect, the template nucleic acid is DNA. In another
aspect, the template is RNA. Suitable nucleic acid molecules are
DNA, including genomic DNA, ribosomal DNA and cDNA. Other suitable
nucleic acid molecules are RNA, including mRNA, rRNA and tRNA. The
nucleic acid molecule can be naturally occurring, as in genomic
DNA, or it may be synthetic, ie., prepared based up human action,
or may be a combination of the two. The nucleic acid molecule can
also have certain modification such as 2'-deoxy,
2'-deoxy-2'-fluoro, 2'-O-methyl, 2'-O-methoxyethyl (2'-O-MOE),
2'-O-aminopropyl (2'-O-AP), 2'-O-dimethylaminoethyl (2'-O-DMAOE),
2'-O-dimethylaminopropyl (2'-O-DMAP),
2'-O-dimethylaminoethyloxyethyl (2'-O-DMAEOE), or
2'-O--N-methylacetamido (2'-O-NMA), cholesterol addition, and
phosphorothioate backbone as described in US Patent Application
20070213292; and certain ribonucleoside that are is linked between
the 2'-oxygen and the 4'-carbon atoms with a methylene unit as
described in U.S. Pat. No. 6,268,490, wherein both patent and
patent application are incorporated hereby reference in their
entirety.
[0078] The term "vector", as used herein, refers to a nucleic acid
construct designed for delivery to a host cell or transfer between
different host cells. As used herein, a vector can be viral or
non-viral.
[0079] As used herein, the term "expression vector" refers to a
vector that has the ability to incorporate and express heterologous
nucleic acid fragments in a cell. An expression vector may comprise
additional elements, for example, the expression vector may have
two replication systems, thus allowing it to be maintained in two
organisms, for example in human cells for expression and in a
prokaryotic host for cloning and amplification.
[0080] As used herein, the term "heterologous nucleic acid
fragments" refers to nucleic acid sequences that are not naturally
occurring in that cell. For example, when a miR-150 gene is
inserted into the genome of a bacteria or virus, that miR-150 gene
is heterologous to that recipient bacteria or virus because the
bacteria and viral genome do not naturally have the miR-150
gene.
[0081] As used herein, the term "viral vector" refers to a nucleic
acid vector construct that includes at least one element of viral
origin and has the capacity to be packaged into a viral vector
particle. The viral vector can contain the miR-150 gene in place of
non-essential viral genes. The vector and/or particle may be
utilized for the purpose of transferring any nucleic acids into
cells either in vitro or in vivo. Numerous forms of viral vectors
are known in the art.
[0082] The term "replication incompetent" as used herein means the
viral vector cannot further replicate and package its genomes. For
example, when the cells of a subject are infected with replication
incompetent recombinant adeno-associated virus (rAAV) virions, the
heterologous (also known as transgene) gene is expressed in the
patient's cells, but, the rAAV is replication defective (e.g.,
lacks accessory genes that encode essential proteins from packaging
the virus) and viral particles cannot be formed in the patient's
cells.
[0083] The term "gene" means the nucleic acid sequence which is
transcribed (DNA) to RNA in vitro or in vivo when operably linked
to appropriate regulatory sequences. The gene may or may not
include regions preceding and following the coding region, e.g. 5'
untranslated (5'UTR) or "leader" sequences and 3' UTR or "trailer"
sequences, as well as intervening sequences (introns) between
individual coding segments (exons).
[0084] As used herein, "identity", in the context of two or more
nucleic acids sequences, refers to two or more sequences or
subsequences that are the same or have a specified percentage of
nucleotides that are the same (i.e., about 60% identity, preferably
65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,
98%, 99%, or higher identity over a specified region, when compared
and aligned for maximum correspondence over a comparison window or
designated region) when the sequences are aligned to maximize
sequence matching, i.e., taking into account gaps and insertions,
such as when using a BLAST or BLAST 2.0 sequence comparison
algorithms with default parameters described below, or by manual
alignment and visual inspection. Such sequences are then said to be
"substantially identical." This term also refers to, or can be
applied to, the complement of a test sequence. The term also
includes sequences that have deletions and/or additions, as well as
those that have substitutions. As described below, the preferred
algorithms can account for gaps and the like. Preferably, identity
exists over a region that is at least about 25 nucleotides in
length, or more preferably over a region that is 50-100 nucleotides
in length. For sequence comparison, typically one sequence acts as
a reference sequence, to which test sequences are compared. When
using a sequence comparison algorithm, test and reference sequences
are input into a computer, subsequence coordinates are designated,
if necessary, and sequence algorithm program parameters are
designated. The sequence comparison algorithm then calculates the
percent sequence identity for the test sequence(s) relative to the
reference sequence, based on the designated program parameters.
[0085] For sequence comparison, typically one sequence acts as a
reference sequence, to which test sequences are compared. When
using a sequence comparison algorithm, test and reference sequences
are entered into a computer, subsequence coordinates are
designated, if necessary, and sequence algorithm program parameters
are designated. Preferably, default program parameters can be used,
or alternative parameters can be designated. The sequence
comparison algorithm then calculates the percent sequence
identities for the test sequences relative to the reference
sequence, based on the program parameters.
[0086] A "comparison window", as used herein, includes reference to
a segment of any one of the number of contiguous positions selected
from the group consisting of from 20 to 600, usually about 50 to
about 200, more usually about 100 to about 150 in which a sequence
can be compared to a reference sequence of the same number of
contiguous positions after the two sequences are optimally aligned.
Methods of alignment of sequences for comparison are well-known in
the art. Optimal alignment of sequences for comparison can be
conducted, e.g., by the local homology algorithm of Smith &
Waterman, Adv. Appl. Math. 2: 482, 1981, by the homology alignment
algorithm of Needleman & Wunsch, J. Mol. Biol. 48: 443, 1970,
by the search for similarity method of Pearson & Lipman, Proc.
Nat'l. Acad. Sci. USA 85: 2444, 1988, by computerized
implementations of these algorithms (GAP, BESTFIT, FASTA, and
TFASTA in the Wisconsin Genetics Software Package, Genetics
Computer Group, 575 Science Dr., Madison, Wis.), or by manual
alignment and visual inspection (see, e.g., Current Protocols in
Molecular Biology, Ausubel et al., eds. 1995 supplement)).
[0087] Identity can be readily calculated by known methods,
including but not limited to those described in (Computational
Molecular Biology, Lesk, A. M., ea., Oxford University Press, New
York, 1988; Biocomputing: Informatics and 14 Genome Projects,
Smith, D. W., ea., Academic Press, New York, 1993; Computer
Analysis of Sequence Data, Part I, Griffin, A. M., and Griffin, H.
G., eds., Humana Press, New Jersey, 1994; Sequence Analysis in
Molecular Biology, von Heinje, G., Academic Press, 1987; and
Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M
Stockton Press, New York, 1991; and Carillo, H., and Lipman, D.,
SIAM J. Applied Math., 48: 1073 (1988)). Methods to determine
identity are designed to give the largest match between the
sequences tested. Moreover, methods to determine identity are
codified in publicly available computer programs such as
BLASTP.
[0088] Where necessary or desired, optimal alignment of sequences
for comparison can be conducted, for example, by the local homology
algorithm of Smith and Waterman (Adv. Appl. Math. 2:482 (1981),
which is incorporated by reference herein), by the homology
alignment algorithm of Needleman and Wunsch (J. Mol. Biol.
48:443-53 (1970), which is incorporated by reference herein), by
the search for similarity method of Pearson and Lipman (Proc. Natl.
Acad. Sci. USA 85:2444-48 (1988), which is incorporated by
reference herein), by computerized implementations of these
algorithms (e.g., GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin
Genetics Software Package, Genetics Computer Group, 575 Science
Dr., Madison, Wis.), or by visual inspection. (See generally
Ausubel et al. (eds.), Current Protocols in Molecular Biology, 4th
ed., John Wiley and Sons, New York (1999)).
[0089] One example of a useful algorithm is PILEUP. PILEUP creates
a multiple sequence alignment from a group of related sequences
using progressive, pairwise alignments to show the percent sequence
identity. It also plots a tree or dendogram showing the clustering
relationships used to create the alignment. PILEUP uses a
simplification of the progressive alignment method of Feng and
Doolittle (J. Mol. Evol. 25:351-60 (1987), which is incorporated by
reference herein). The method used is similar to the method
described by Higgins and Sharp (Comput. Appl. Biosci. 5:151-53
(1989), which is incorporated by reference herein). The program can
align up to 300 sequences, each of a maximum length of 5,000
nucleotides or amino acids. The multiple alignment procedure begins
with the pairwise alignment of the two most similar sequences,
producing a cluster of two aligned sequences. This cluster is then
aligned to the next most related sequence or cluster of aligned
sequences. Two clusters of sequences are aligned by a simple
extension of the pairwise alignment of two individual sequences.
The final alignment is achieved by a series of progressive,
pairwise alignments. The program is run by designating specific
sequences and their amino acid or nucleotide coordinates for
regions of sequence comparison and by designating the program
parameters. For example, a reference sequence can be compared to
other test sequences to determine the percent sequence identity
relationship using the following parameters: default gap weight
(3.00), default gap length weight (0.10), and weighted end
gaps.
[0090] Another example of an algorithm that is suitable for
determining percent sequence identity and sequence similarity is
the BLAST algorithm, which is described by Altschul et al. (J. Mol.
Biol. 215:403-410 (1990), which is incorporated by reference
herein). (See also Zhang et al., Nucleic Acid Res. 26:3986-90
(1998); Altschul et al., Nucleic Acid Res. 25:3389-402 (1997),
which are incorporated by reference herein). Software for
performing BLAST analyses is publicly available through the
National Center for Biotechnology Information internet web site.
This algorithm involves first identifying high scoring sequence
pairs (HSPs) by identifying short words of length W in the query
sequence, which either match or satisfy some positive-valued
threshold score T when aligned with a word of the same length in a
database sequence. T is referred to as the neighborhood word score
threshold (Altschul et al. (1990), supra). These initial
neighborhood word hits act as seeds for initiating searches to find
longer HSPs containing them. The word hits are then extended in
both directions along each sequence for as far as the cumulative
alignment score can be increased. Extension of the word hits in
each direction is halted when: the cumulative alignment score falls
off by the quantity X from its maximum achieved value; the
cumulative score goes to zero or below, due to the accumulation of
one or more negative-scoring residue alignments; or the end of
either sequence is reached. The BLAST algorithm parameters W, T,
and X determine the sensitivity and speed of the alignment. The
BLAST program uses as defaults a word length (W) of 11, the
BLOSUM62 scoring matrix (see Henikoff and Henikoff, Proc. Natl.
Acad. Sci. USA 89:10915-9 (1992), which is incorporated by
reference herein) alignments (B) of 50, expectation (E) of 10, M=5,
N=-4, and a comparison of both strands.
[0091] In addition to calculating percent sequence identity, the
BLAST algorithm also performs a statistical analysis of the
similarity between two sequences (see, e.g., Karlin and Altschul,
Proc. Natl. Acad. Sci. USA 90:5873-77 (1993), which is incorporated
by reference herein). One measure of similarity provided by the
BLAST algorithm is the smallest sum probability (P(N)), which
provides an indication of the probability by which a match between
two nucleotide or amino acid sequences would occur by chance. For
example, an amino acid sequence is considered similar to a
reference amino acid sequence if the smallest sum probability in a
comparison of the test amino acid to the reference amino acid is
less than about 0.1, more typically less than about 0.01, and most
typically less than about 0.001.
[0092] As used herein, the term "a progenitor cell" refers to refer
to an immature or undifferentiated cell that has the potential
later on to mature (differentiate) into a specific cell type, for
example, a blood cell, a skin cell, a bone cell, or a hair cells. A
progenitor cell also can proliferate to make more progenitor cells
that are similarly immature or undifferentiated.
[0093] As used herein, the term "hematopoietic progenitor cell"
refers to progenitor cells that can differentiate into the
hematopoietic lineage and give rise to all blood cell types such as
white blood cells and red blood cells.
[0094] As used herein, the term "microRNA or miRNA" refers to a
microRNA molecule found in eukaryotes that is involved in RNA-based
gene regulation. See, e.g., Carrington and Ambros, 2003, Science,
301(5631):336-8 which is hereby incorporated by reference in its
entirety. miRNA are single-stranded RNA molecules of about 21-23
nucleotides in length, which regulate gene expression. miRNAs are
encoded by genes that are transcribed from DNA but not translated
into protein (non-coding RNA); instead they are processed from
primary transcripts known as pri-miRNA to short stem-loop
structures called pre-miRNA and finally to functional miRNA. Mature
miRNA molecules are partially complementary to one or more
messenger RNA (mRNA) molecules, and their main function is to
downregulate gene expression. The term will be used to refer to the
RNA molecule processed from a precursor pre-miRNA.
[0095] Unless otherwise explained, all technical and scientific
terms used herein have the same meaning as commonly understood by
one of ordinary skill in the art to which this disclosure belongs.
Definitions of common terms in hematology and molecular biology can
be found in The Merck Manual of Diagnosis and Therapy, 18th
Edition, published by Merck Research Laboratories, 2006 (ISBN
0-911910-18-2); Robert S. Porter et al. (eds.), The Encyclopedia of
Molecular Biology, published by Blackwell Science Ltd., 1994 (ISBN
0-632-02182-9); and Robert A. Meyers (ed.), Molecular Biology and
Biotechnology: a Comprehensive Desk Reference, published by VCH
Publishers, Inc., 1995 (ISBN 1-56081-569-8). Definitions of common
terms in molecular biology may be found in Benjamin Lewin, Genes V,
published by Oxford University Press, 1994 (ISBN 0-19-854287-9);
Kendrew et al. (eds.), The Encyclopedia of Molecular Biology,
published by Blackwell Science Ltd., 1994 (ISBN 0-632-02182-9); and
Robert A. Meyers (ed.), Molecular Biology and Biotechnology: a
Comprehensive Desk Reference, published by VCH Publishers, Inc.,
1995 (ISBN 1-56081-569-8).
[0096] Unless otherwise stated, the present invention was performed
using standard procedures, as described, for example in Maniatis et
al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor
Laboratory Press, Cold Spring Harbor, N.Y., USA (1982); Sambrook et
al., Molecular Cloning: A Laboratory Manual (2 ed.), Cold Spring
Harbor Laboratory Press, Cold Spring Harbor, N.Y., USA (1989);
Davis et al., Basic Methods in Molecular Biology, Elsevier Science
Publishing, Inc., New York, USA (1986); Methods in Enzymology:
Guide to Molecular Cloning Techniques Vol. 152, S. L. Berger and A.
R. Kimmerl Eds., Academic Press Inc., San Diego, USA (1987));
Current Protocols in Molecular Biology (CPMB) (Fred M. Ausubel, et
al. ed., John Wiley and Sons, Inc.); Current Protocols in Protein
Science (CPPS) (John E. Coligan, et. al., ed., John Wiley and Sons,
Inc.); Current Protocols in Immunology (CPI) (John E. Coligan, et.
al., ed. John Wiley and Sons, Inc.); Current Protocols in Cell
Biology (CPCB) (Juan S. Bonifacino et. al. ed., John Wiley and
Sons, Inc.); Culture of Animal Cells: A Manual of Basic Technique
by R. Ian Freshney, Publisher: Wiley-Liss; 5th edition (2005);
Animal Cell Culture Methods (Methods in Cell Biology, Vol 57,
Jennie P. Mather and David Barnes editors, Academic Press, 1st
edition, 1998) which are all incorporated by reference herein in
their entireties.
[0097] It should be understood that this invention is not limited
to the particular methodology, protocols, and reagents, etc.,
described herein and, as such, may vary. The terminology used
herein is for the purpose of describing particular embodiments
only, and is not intended to limit the scope of the present
invention, which is defined solely by the claims.
[0098] Other than in the operating examples, or where otherwise
indicated, all numbers expressing quantities of ingredients or
reaction conditions used herein should be understood as modified in
all instances by the term "about." The term "about" when used in
connection with percentages may mean.+-.1%.
[0099] The singular terms "a," "an," and "the" include plural
referents unless context clearly indicates otherwise. Similarly,
the word "or" is intended to include "and" unless the context
clearly indicates otherwise. It is further to be understood that
all base sizes or amino acid sizes, and all molecular weight or
molecular mass values, given for nucleic acids or polypeptides are
approximate, and are provided for description. Although methods and
materials similar or equivalent to those described herein can be
used in the practice or testing of this disclosure, suitable
methods and materials are described below. The term "comprises"
means "includes." The abbreviation, "e.g." is derived from the
Latin exempli gratia, and is used herein to indicate a non-limiting
example. Thus, the abbreviation "e.g." is synonymous with the term
"for example."
[0100] All patents and other publications identified are expressly
incorporated herein by reference for the purpose of describing and
disclosing, for example, the methodologies described in such
publications that might be used in connection with the present
invention. These publications are provided solely for their
disclosure prior to the filing date of the present application.
Nothing in this regard should be construed as an admission that the
inventors are not entitled to antedate such disclosure by virtue of
prior invention or for any other reason. All statements as to the
date or representation as to the contents of these documents is
based on the information available to the applicants and does not
constitute any admission as to the correctness of the dates or
contents of these documents.
EMBODIMENTS OF THE INVENTIONS
[0101] Embodiments of the methods disclosed herein are based on the
discovery that a microRNA (miRNAs), miR-150, regulates the
differentiation of megakaryocyte-erythrocyte progenitor cells
(MEPs) from the bone marrow. The regulation of the developmental
fate of multi-potential cells is not well known and the process by
which bipotential hematopoietic progenitor cells are driven to
become either red blood cells or platelets is not understood. The
inventors discovered that miRNAs control mammalian cell fate of the
multi-potential MEPs, in particular, miR-150 modulates lineage fate
in MEPs. The inventors found that miR-150 is preferentially
expressed in the megakaryocytic lineage and that miR-150 expression
in MEPs drives MEP differentiation toward megakaryocytes at the
expense of erythroid cells in vitro and in vivo.
[0102] In experiments using human bone marrow hematopoietic
progenitor cells, overexpression of the miR-150 gene resulted in a
significant increase in megakaryocyte colony forming units (CFU-Mk)
differentiating from MEPs with a concomitant decrease in erythroid
colony forming units. When similar miR-150 overexpression
experiments were conducted with murine bone marrow hematopoietic
progenitor cells and the resultant miR-150 overexpressing
progenitor cells were transplanted back into the animal, the mice
exhibited a larger population of megakaryocytes and a greater
number of platelets compared to control mice. miR-150 expression
led to a bona fide increase in bone marrow megakaryocytes that were
competent to produce mature platelets in circulation. MiR-150
expression induces a blockage in the earliest definable stage of
erythropoiesis, in addition to causing a significant reduction in
the total erythroid population. Accordingly, an increase amount of
miR-150 regulates the differentiation of MEPs and the
post-commitment megakaryocyte expansion.
[0103] While overexpression of miR-150 leads to pro-megakaryocyte
differentiation and an increase in platelet count, the inhibition
of miR-150 expression results in more erythroid colony forming
units, more erythrocytes production and a corresponding decrease in
CFU-Mk. In an artificial model of induced anemia, an inhibition of
miR-150 with a specific antagomir elevated the erythrocyte count in
the model animal. Clearly, one of the roles of miR-150 is in vivo
is to regulate the differentiation of bi-potential MEPs and the
production of RBCs and platelets.
[0104] MicroRNAs (miRNAs) are a class of 18-24 nt non-coding RNAs
(ncRNAs) that exist in a variety of organisms, including mammals,
and are conserved in evolution. miRNAs are transcribed as 5'-capped
large polyadenylated transcripts (pri-miRNA), primarily in a Pol
II-dependent manner. Approximately 40% of human miRNAs are
co-transcribed as clusters encoding up to eight distinct miRNA
sequences in a single pri-microRNA transcript. Many miRNAs can be
encoded in intergenic regions, hosted within introns of pre-mRNAs
or within ncRNA genes. Many miRNAs also tend to be clustered and
transcribed as polycistrons and often have similar spatial temporal
expression patterns. mRNAs have been found to have roles in a
variety of biological processes including developmental timing,
differentiation, apoptosis, cell proliferation, organ development,
and metabolism (Kloosterman, et al., 2006 Dev Cell 11:441-50, and
Krutzfeldt, et al., 2006 Cell Metab 4:9-12). Furthermore, miRNAs
have been implicated in diseases such as cancer (Esquela-Kerscher,
et al., 2006 Nat Rev Cancer 6:259-69) and hepatitis C (Jopling, et
al., 2005 Science 309:1577-81), which make them attractive new drug
targets. In contrast to the widely used RNAi technology using small
interfering RNA (siRNA) duplexes, strategies to inhibit miRNAs have
been less well investigated. Reverse-complement 2'-O-methyl sugar
modified RNA is frequently being used to block miRNA function in
cell-based systems (Krutzfeldt, et al., 2006 Nat Genet
38:S14-9).
[0105] Pri-miRNAs are cleaved within the nucleus by the
microprocessor complex consisting of Drosha, an RNaseIII-type
nuclease and a protein co-factor, DGCR8 (DiGeorge syndrome critical
region 8 gene) in humans, Pasha in Drosophila. The resulting 60-70
nucleotide hairpin structure (pre-miRNA) encodes for a single miRNA
sequence that is exported from the nucleus to the cytoplasm by
Exportin5 in a Ran-GTP dependent manner. Cytoplasmic pre-miRNAs are
further cleaved, by another RNaseIII-nuclease, Dicer in concert
with cofactors (TRBP and PACT in humans), to remove the loop
sequence forming a short-lived asymmetric duplex intermediate
(miRNA: miRNA *). The microRNA: microRNA * duplex is in turn loaded
into the miRISC complex in which Argonaut (Ago) proteins appear to
be the key effector molecules. The strand that becomes the active
mature microRNA appears to be dependent upon which has the lowest
free energy 5' end and the other strand is degraded by an unknown
nuclease .
[0106] Accordingly, in one embodiment, disclosed herein is a method
of treating thrombocytopenia in a host in need thereof, the method
comprising administering to a host an effective amount of an agent
that increases miR-150 expression in a cell.
[0107] Thrombocytopenia is a deficiency of platelets
(thrombocytes). Platelets come from megakaryocytes, which are
produced in the bone marrow from hematopoietic progenitor cells.
When abnormalities develop in the marrow, the marrow cells can lose
their ability to produce platelets in correct amounts. The result
is a lower than normal level of platelets in the blood. Drugs used
in cancer chemotherapy can cause the marrow to malfunction in this
way, as can the presence of tumor cells in the marrow itself.
[0108] Normally, the spleen holds about one-third of the body's
platelets as part of this organ's function to recycle aging or
damaged RBCs. When liver disease or cancer of the spleen is
present, the spleen can enlarge, resulting in a greater number of
platelets staying in the organ. This condition then results in
abnormally low numbers of platelets in the blood.
[0109] Platelets can break down in unusually high amounts in
persons with abnormalities in their blood vessel walls; with blood
clots; or with man-made replacement heart valves. Devices placed
inside blood vessels to keep them from closing (stents) due to
weakened walls or fat build-up can also cause platelets to break
down. In addition, infections and other changes in the immune
system can speed up the removal of platelets from the
circulation.
[0110] Thrombocytopenia generally means a circulating platelet
count of less than the normal circulating range, e.g., less than
about 1.6.times.10.sup.5/mm.sup.3, less than about
1.5.times.10.sup.5/mm.sup.3, less than about
1.3.times.10.sup.5/mm.sup.3 or less than about
1.0.times.10.sup.5/mm.sup.3. Under the common terminology criteria
for adverse events, version 3.0, grade 1 thrombocytopenia is the
lower normal limit to 75,000 platelets/mm.sup.3, grade 2
thrombocytopenia is <75,000-50,000 platelets/mm.sup.3, grade 3
thrombocytopenia is <50,000-25,000 platelets/mm.sup.3 and grade
4 is <25,000 platelets/mm.sup.3
[0111] The host needing treatment for thrombocytopenia can be any
animal that has platelets, the platelets are produced from
megakaryocytes, and the megakaryocytes are differentiated from
hematopoietic progenitor cells. In one embodiment, the host is a
mammal, such as a dog, cat, horse, and monkey, preferably a
human.
[0112] A platelet count is performed to determine the number of
platelets in circulation and on the basis of the platelet counts,
the physician can determine whether the host has thrombocytopenia.
A platelet count is part of the complete blood count test (CBC)
routinely ordered by physicians. A platelet count is a test to
measure platelets that are present in the peripheral circulating
blood of a host. This test can be performed by skilled medical
personnel such as physicians, nurses and trained laboratory
technicians by methods-known in the art. For example, a sample of
peripheral blood is drawn into anticoagulant to prevent the blood
from clotting. The larger and heavier cells: white blood cells and
RBCs are sedimented by low speed centrifugation (1000.times.G, 10
min) and the platelet-rich liquid fraction of the blood is
collected and counted. Other manual methods of determining platelet
counts include visual evaluation of blood smears on microscope
slides and methods using RBCs-lysing agents followed by visual
platelet counting. In one embodiment, platelets are determined
using automated blood counting machines that include but are not
limited to the Sysmex XE-2100, the Abbott Cell-Dyn range (e.g.
Cell-Dyn 3500), Boule Nordic AB Ca530 Vet and Melet Schloesing MS4.
In one embodiment, the platelet count is performed according to the
European Patent EP1123510 and U.S. Pat. No. 6,872,572, both of
which are hereby incorporated by reference in their entirety.
[0113] In one embodiment, the cell from a host needing treatment
for thrombocytopenia wherein the miR-150 expression is increased is
a progenitor cell. In another embodiment, the progenitor cell is a
hematopoietic progenitor cell.
[0114] In one aspect, an agent that increases the miR-150
expression in a cell of a host comprises a vector comprising a
nucleic acid sequence that is at least 90% identical to SEQ. ID.
No. 1. In other aspects, the nucleic acid is at least 92%, at least
94%, at least 95%, at least 97%, at least 99%, and all the
intermediate percentages between 90% and 100%, identical to SEQ.
ID. No. 1. The differences from SEQ. ID. No. 1 should be such that
the overall hairpin structure of the pri-miR-150 is maintain.
[0115] In another aspect, the vector is a virus. In yet another
aspect, the vector is a non-viral vector.
[0116] In one embodiment, an agent that increases miR-150
expression in a cell of a host comprises a nucleic acid sequence
that is at least 90% identical to SEQ. ID. No. 1. In another
embodiment, the nucleic acid is at least 92%, at least 94%, at
least 95%, at least 97%, at least 99%, and all the intermediate
percentages between 90% and 100%, identical to SEQ. ID. No. 1.
[0117] The SEQ. ID. No. 1 provides the Homo sapiens miR-150
stem-loop pri-miRNA which is also known as has-mir-150, M10000479,
NT.sub.--111109, or miRBase:MI0000479 at the miRBase at the Sanger
Institute (world wide web "period" microRNA "period" Sanger
"period" ac "period" uk).
[0118] While not wishing to be bound by theory, expression of the
miR-150 gene or a nucleic acid that is at least 90% identical to
SEQ. ID. No. 1 by gene transcription produces a primary transcript,
pre-miR-150, that can fold into a stem-loop structure. The
pre-miR-150 can be exported out of the nucleus and be processed in
the cytoplasm into a duplex miR-150 from which a mature miR-150
(SEQ. ID. 2) (miRBase:MIMAT0000451) becomes available for upload
into the miRISC (the miRNA gene inhibition complex). A vector
comprising a nucleic acid that is at least 90% identical to SEQ.
ID. No. 1, when transfected into a host cell, introduces the
miR-150 gene as a transgene into the host cell. In this transfected
host cell harboring the miR1-50 transgene, overexpression of the
miR-150 transgene increases the amount of miR-150 in the cell.
Excess amounts of miR-150 can lead to enhanced repression of genes
naturally regulated by miR-150.
[0119] In one embodiment, a vector comprising a nucleic acid that
is at least 90% identical to SEQ. ID. No. 1 is an expression
vector. The expression vector can have a strong promoter sequence
driving the robust mammalian transcription of the miR-150 transgene
in the host cell. Strong promoter sequences include but are not
limited to the Moloney murine leukemia virus promoter,
cytomegalovirus promoter, the simian virus 40 early region
promoter, the lymphotrophic papovavirus, and the human beta-globin
gene promoter sequences. In one embodiment, the promoter can be
chimeric sequences from several promoter types as described in U.S.
Pat. No. 6,136,536 which is incorporated hereby reference in its
entirety. In another embodiment, the promoter can be the human
osteocalcin (hOC) promoter (McCarthy H. O., et. al., 2007, J. Gene
Medicine, 9: 511-20).
[0120] In one embodiment, the expression vector can be a virus such
as an adenovirus, an adeno-associated virus, or lentivirus, for
example, MDH.xdna murine retroviral vector. Viral vectors provide
an additional advantage of ease of transfecting the host cell by
viral infection. In another embodiment, the expression in a
non-viral vector. Such vectors can be transfected into host cells
using known transfection methods known in the art, such as cationic
lipid transfection.
[0121] By increasing the miR-150 expression in the hematopoietic
progenitor cells of a host, the differentiation of the
hematopoietic progenitor cells can be shifted to producing more
megakaryocytes, from which platelets are derived, eventually
increasing the platelet count.
[0122] In one embodiment, disclosed herein is a method of treating
thrombocytopenia in a host in need thereof, comprises: (a)
contacting the hematopoietic progenitor cells with a vector
comprising a nucleic acid sequence that is at least 90% identical
to SEQ. ID. No. 1; and (b) introducing the cell carrying the
transgene into the host.
[0123] The method comprises obtaining a sample of hematopoietic
progenitor cells from a host.
[0124] In one embodiment, the hematopoietic progenitor cells are
isolated from host, transfected, cultured, and transplanted back
into the same host, i.e. an autologous cell transplant. In another
embodiment, the hematopoietic progenitor cells are isolated from a
donor who is an HLA-type match with a host (recipient) who is
diagnosed with thrombocytopenia. Donor-recipient antigen
type-matching is well known in the art. The HLA-types include
HLA-A, HLA-B, HLA-C, and HLA-D. These represent the minimum number
of cell surface antigen matching required for transplantation. The
donor's hematopoietic progenitor cells can be transfected with a
vector or nucleic acid comprising the nucleic acid that is at least
90% identical to SEQ. ID. No. 1 (the miR-150 transgene), culture
expanded, and then transplanted into the host.
[0125] In one embodiment, the method disclosed herein includes
monitoring the platelet count of a host before and after the
administration of the agent for treatment of thrombocytopenia. The
platelet count performed before treatment provides the data for a
physician to make a diagnosis of thrombocytopenia and the platelet
count also serves a reference number from which after the treatment
platelet counts can be compared. Routine platelet count of samples
of peripheral blood should be performed at 1, 2, 3 months or every
bimonthly after treatment or according to physician's decision in
order to monitor the efficacy of the treatment.
[0126] In one embodiment, disclosed herein is a method of treating
anemia in a host in need thereof, the method comprising
administering an effective amount of an agent that inhibits miR-150
expression in a cell to a host.
[0127] Anemia generally means a red cell mass corresponding to less
than about 4.0.times.10.sup.12 red cells/L in adult females and
less than about 4.5.times.10.sup.12 red cells/L in adult males (a
hemoglobin level of less than about 12.0 g/dL in adult females and
less than about 13.5 g/dL in adult males). Anemia may occur as a
result of bleeding (including internal), hemolysis, kidney disease,
leukemia, multiple myeloma, bone marrow failure, erythropoietin
deficiency, or deficiencies in iron, folate, vitamin B12, or
vitamin B6.
[0128] The RBCs count is also a part of the complete blood count
test (CBC) routinely ordered by physicians. A sample of peripheral
blood can be collected and mixed with anticoagulant. For RBC
counting by the manual visual method, a small, fixed volume of
blood is diluted, applied to a hemacytometer and counted under a
microscope. Alternatively, RBCs are counted with automated cell
counters described herein.
[0129] In one embodiment, a host needing treatment for anemia can
be any animal that has RBCs (erythrocytes), and the RBCs are
differentiated from hematopoietic progenitor cells. In one
embodiment, the host is a mammal, such as a dog, cat, horse, and
monkey, preferably a human.
[0130] In one embodiment, the cell in a host wherein the miR-150
activity is inhibited, is a progenitor cell. In another embodiment,
a progenitor cell wherein the miR-150 activity is inhibited is a
hematopoietic progenitor cell.
[0131] In one embodiment, an agent that inhibits miR-150 activity
in a cell comprises a nucleic acid sequence that can form
complementary base-pairing with SEQ. ID. No. 2, the mature miR-150,
for at least 90% of the bases of SEQ. ID. No. 2. In one aspect, the
nucleic acid can form complementary base-pairing with at least 92%,
at least 94%, at least 95%, at least 97%, at least 99%, and all the
intermediate percentages between 90% and 100%, to SEQ. ID. No.
2.
[0132] In another embodiment, an agent is a vector comprising a
nucleic acid sequence that is at least 90% identical to SEQ. ID.
No. 3 (miRBase:MIMAT0004610). The nucleic acid is at least 92%, at
least 94%, at least 95%, at least 97%, at least 99%, and all the
intermediate percentages between 90% and 100%, identical to SEQ.
ID. No. 3. In yet another embodiment, an agent is a nucleic acid
sequence that is at least 90% identical to SEQ. ID. No. 3.
[0133] In some aspects, an agent that inhibits miR-150 activity in
a cell can be referred to as a miR-150 inhibitor, the miR-150
inhibitor functions by blocking, preventing, and/or antagonizing
the normal cellular activity of the mature miR-150 which is to down
regulate the expressions of certain genes. A miR-150 inhibitor can
be an antagomir of miR-150, an antisense oligonucleotide to
miR-150, a locked nucleic acid that anneals to miR-150, and
double-stranded RNA corresponding to miR-150 (dsRNA).
[0134] In one embodiment, a miR-150 inhibitor is between 17 and 25
nucleotides in length and that comprises a 5' to 3' sequence that
is at least 90% complementary to the 5' to 3' sequence of SEQ. ID.
No. 2. In another embodiment, a miR-150 inhibitor is a synthetic
RNA molecule of between 17 and 125 residues in length comprising i)
an miRNA region whose sequence from 5' to 3' is identical to a
mature miR-150 sequence, and ii) a complementary region whose
sequence from 5' to 3' is between 60% and 100% complementary to the
mature miR-150 sequence.
[0135] Antagomirs are a novel class of chemically engineered
oligonucleotides that block the activity of miRNAs and essentially
"silence" the miRNA (Krutzfeldt J, et. al., 2005, Nature 438:
685-9). Antagomirs are single-stranded RNA that are perfectly
complementary to their miRNA except that they are 2'-O-methyl
(2'-OMe) oligoribonucleotides and are also linked to cholesterol at
the 3' end. Both these modifications, 2'-OMe and cholesterol, aid
in the antagomir stability in vivo and ease of entry into the
cells. Methods of designing and synthesizing antagomirs and the
various modifications (e.g. 2'-O-Methoxyethyl) are described in US
Pat. Application 20070213292 and is hereby incorporated by
reference in its entirety. An example of a miR-150 antagomir is 5'
mC(*)mA(*)mCmUmGmGmUmAmCmAmAmGmGmGmUmUmGmGmG(*)mA(*)mG
(*)mA(*)(3'-Chl) 3' (SEQ. ID. No. 23). The mN: 2'OMe base; *:
phosphorothioate linkage; Chl: cholesterol.
[0136] In one embodiment, the miR-150 inhibitor is a miR-150
antagomir. In one embodiment, the miR-150 inhibitor is SEQ. ID. No.
23. In another embodiment, the miR-150 inhibitor consist
essentially of SEQ. ID. No. 23. In another embodiment, the miR-150
inhibitor consist of SEQ. ID. No. 23. In another embodiment, the
miR-150 inhibitor comprises SEQ. ID. No. 23.
[0137] Locked nucleic acid (LNA)-modified oligonucleotides are
distinctive 2'-O-modified RNA in which the 2'-O-oxygen is bridged
to the 4'-position via a methylene linker to form a rigid bicycle,
locked into a C3'-endo (RNA) sugar conformation (Vester B., et.
al., Biochemistry 2004; 43: 13233-13241). The LNA modification
leads to the thermodynamically strongest duplex formation with
complementary RNA known. Consequently, a biological activity is
often attained with very short LNA oligonucleotides. For example,
an 8 nt fully-modified LNA oligomer complementary to a structural
loop inhibited 50% of self-splicing of group I introns from rRNA
genes in pathogenic organisms whereas DNA and RNA oligonucleotides
were ineffective. Short fully-modified LNA oligonucleotides
designed against telomerase were active in cellular assays,
compared to mismatched negative controls. Furthermore, LNAs display
excellent mismatch discrimination. Mouritzen et al. (Expert Rev Mol
Diagn 2003; 3: 27-38) showed single-nucleotide specificity against
complementary DNA using fully modified 12 nucleotide LNA probes
coupled to glass slides during the development of a microarray used
to probe samples for single-nucleotide polymorphisms (SNPs)
associated with human dysmetabolic syndrome. The synthesis and
incorporation of LNA bases can be achieved by using standard DNA
synthesis chemistry and described in U.S. Pat. No. 6,268,490 and is
hereby incorporated by reference in its entirety.
[0138] An anti-sense oligonucleotide of miR-150 has a sequence that
perfectly complementary to SEQ. ID. No. 2, the mature miR-150.
Complementary pairing between an anti-sense oligonucleotide of
miR-150 and miR-150 produces a duplex RNA that is highly
susceptible to RNase degradation. An anti-sense oligonucleotide of
miR-150 comprises the sequence 5'-CACUGGUACAAGGGUUGGGAGA-3' (SEQ.
ID. No. 4).
[0139] One skilled in the art can also readily determine an
appropriate dosage regimen for administering a compound that
inhibits miRNA expression to a given subject, as described herein.
Suitable compounds for inhibiting miRNA gene expression include
double-stranded RNA (such as short- or small-interfering RNA or
"siRNA"), antisense nucleic acids, and enzymatic RNA molecules,
such as ribozymes. Each of these compounds can be targeted to a
given miRNA gene product and interfere with the expression (e.g.,
by inhibiting translation, by inducing cleavage and/or degradation)
of the target miRNA gene product. For example, expression of a
given miRNA gene can be inhibited by inducing RNA interference of
the miRNA gene with an isolated double-stranded RNA ("dsRNA")
molecule which has at least 90%, for example at least 95%, at least
98%, at least 99%, or 100%, sequence homology with at least a
portion of the miRNA gene product. In a particular embodiment, the
dsRNA molecule is a "short or small interfering RNA" or "siRNA."
siRNA useful in the present methods comprise short double-stranded
RNA from about 17 nucleotides to about 29 nucleotides in length,
preferably from about 19 to about 25 nucleotides in length. The
siRNA comprise a sense RNA strand and a complementary antisense RNA
strand annealed together by standard Watson-Crick base-pairing
interactions (hereinafter "base-paired")--The sense strand
comprises a nucleic acid sequence that is substantially identical
to a nucleic acid sequence contained within the target miRNA gene
product.
[0140] In one embodiment, an agent that inhibits miR-150 activity
is a vector that comprises an anti-sense oligonucleotide to miR-150
(SEQ. ID. No. 4). The anti-sense oligonucleotide sequence can be
cloned into a vector for the expression in a host cell by any means
known to one skilled in the art. In one embodiment, the vector is a
virus. In another embodiment, the vector is a non-virus. Designing,
cloning, transfection, and expression of anti-sense
oligonucleotides against miRNAs are described in Scherr M. et. al.,
2007, Nucleic Acid Research 35(22):e149 and is incorporated hereby
reference in its entirety.
[0141] In one embodiment, the agent can be various combinations of
an antagomir of miR-150, an antisense oligonucleotide to miR-150,
dsRNA to miR-150, or a locked nucleic acid that anneals to
miR-150.
[0142] In one embodiment, disclosed herein is a method of treating
anemia in a host in need thereof, the method comprising: (a)
contacting the hematopoietic progenitor cells with a vector
comprising a nucleic acid sequence that is at least 90% identical
to SEQ. ID. No. 3 or 4; and (b) introducing the cell from step b
into the same host. The method comprises obtaining a sample of
hematopoietic progenitor cells from a host. Methods of isolating,
transfecting, culturing, screening for strong expression of
transgene, and transplantation can be performed as described
herein.
[0143] In one embodiment, the method disclosed herein includes
monitoring the RBC count of a host before and after the
administration of the agent for treatment of anemia. The RBC count
performed before treatment provide the data for a physician to make
a diagnosis of anemia and the RBC count also serve a reference
number from which after treatment RBC counts can be compared with.
Routine RBC count of samples of peripheral blood should be
performed at 1, 2, 3 months or every bimonthly after treatment or
according to physician's decision in order to monitor the efficacy
of the treatment.
[0144] In one embodiment, the method disclosed herein comprises
treating anemia in conjunction with other known treatments such as
with erythropoietin (EPO) and peptide mimetics of EPO. EPO is a
hormone produced by the kidney that promotes the formation of red
blood cells in the bone marrow. The kidney cells that make EPO are
specialized and are sensitive to low oxygen levels in the blood.
These cells release EPO when the oxygen level is low in the kidney.
EPO then stimulates the bone marrow to produce more red cells and
thereby increase the oxygen-carrying capacity of the blood. EPO is
the prime regulator of red blood cell production. Its major
functions are to promote the differentiation and development of red
blood cells and to initiate the production of hemoglobin, the
molecule within red cells that transports oxygen.
[0145] In one embodiment, the methods described herein can be
implemented with other therapeutics associated with
thrombocytopenia and anemia.
[0146] The present invention can be defined in any of the following
alphabetized paragraphs: [0147] [A] The use of an agent that
increases miR-150 expression in a cell for the treatment of
thrombocytopenia in a host in need thereof. [0148] [B] The use of
an agent that increases miR-150 expression in a cell in the
manufacture of a medicament for the treatment of thrombocytopenia.
[0149] [C] The use of paragraph [A] or [B], wherein the cell is a
progenitor cell. [0150] [D] The use of paragraph [C], wherein the
progenitor cell is a hematopoietic progenitor cell. [0151] [E] The
use of paragraph [A] or [B], wherein the agent is a vector
comprising a nucleic acid sequence that is at least 90% identical
to SEQ. ID. No. 1. [0152] [F] The use of paragraph [E], wherein the
vector is a virus. [0153] [G] The use of paragraph [A] or [B],
wherein the agent is a nucleic acid sequence that is at least 90%
identical to SEQ. ID. No. 1. [0154] [H] A method of treating
thrombocytopenia in a host in need thereof, the method comprising
administering an effective amount of an agent that increases
miR-150 expression in a cell to a host. [0155] [I] The method of
paragraph [H], wherein the cell is a progenitor cell. [0156] [J]
The method of paragraph [1], wherein the progenitor cell is a
hematopoietic progenitor cell. [0157] [K] The method of paragraph
[H], wherein the agent is a vector comprising a nucleic acid
sequence that is at least 90% identical to SEQ. ID. No. 1. [0158]
[L] The method of paragraph [K], wherein the vector is a virus.
[0159] [M] The method of paragraph [H], wherein the agent is a
nucleic acid sequence that is at least 90% identical to SEQ. ID.
No. 1. [0160] [N] A method of treating thrombocytopenia in a host
in need thereof, the method comprising: [0161] a. obtaining a
sample of hematopoietic progenitor cells from said host; [0162] b.
contacting the hematopoietic progenitor cells with a vector
comprising a nucleic acid sequence that is at least 90% identical
to SEQ. ID. No. 1; and [0163] c. introducing the cell from step b
into the host. [0164] [O] The use of an agent that inhibits miR-150
in a cell for the treatment of anemia in a host in need thereof.
[0165] [P] The use of an agent that inhibits miR-150 in a cell in
the manufacture of a medicament for the treatment of anemia. [0166]
[Q] The use of either paragraph [O] or [P], wherein the cell is a
progenitor cell. [0167] [R] The use of paragraph [Q], wherein the
progenitor cell is a hematopoietic progenitor cell. [0168] [S] The
use of paragraph [O] or [P], wherein the agent is an antagomir of
miR-150, an anti-miR-150 oligonucleotide, an antisense
oligonucleotide to miR-150 or a locked nucleic acid that anneals to
miR-150. [0169] [T] The use of paragraph [O] or [P], wherein the
agent is a vector comprising a nucleic acid sequence that is at
least 90% identical to SEQ. ID. No. 3. [0170] [U] The use of
paragraph [T], wherein the vector is a virus. [0171] [V] A method
of treating anemia in a host in need thereof, the method comprising
administering an effective amount of an agent that inhibits miR-150
in a cell to a host. [0172] [W] The method of paragraph [V],
wherein the cell is a progenitor cell. [0173] [X] The method of
paragraph [W], wherein the progenitor cell is a hematopoietic
progenitor cell. [0174] [Y] The method of paragraph [V], wherein
the agent is a vector comprising a nucleic acid sequence that is at
least 90% identical to SEQ. ID. No. 3. [0175] [Z] The method of
paragraph [V], wherein the agent is an antagomir of miR-150, an
anti-miR-150 oligonucleotide, an antisense oligonucleotide to
miR-150 or a locked nucleic acid that anneals to miR-150. [0176]
[AA] A method of paragraph [Y], wherein the vector is a virus.
[0177] [BB] A method of treating anemia in a host in need thereof,
the method comprising: [0178] a. obtaining a sample of
hematopoietic progenitor cells from said host; [0179] b. contacting
the hematopoietic progenitor cells with a vector comprising a
nucleic acid sequence that is at least 90% identical to SEQ. ID.
No. 3; and [0180] c. introducing the cell from step b into the same
host.
Hematopoietic Progenitor Cells
[0181] Peripheral blood progenitor cells (PBPC) have become the
preferred source of hematopoetic progenitor cells for allogeneic
and autologous transplantation because of technical ease of
collection and shorter time required for engraftment.
Traditionally, granulocyte-colony stimulating factor (G-CSF) has
been used to stimulate more PBPC and release of hematopoetic
progenitor cells from the bone marrow. Although regimens using
G-CSF usually succeed in collecting adequate numbers of PBPC from
healthy donors, 5%-10% will mobilize stem cells poorly and may
require multiple large volume apheresis or bone marrow
harvesting.
[0182] AMD3100, is a bicyclam compound that inhibits the binding of
stromal cell derived factor-1 (SDF-1) to its cognate receptor
CXCR4. CXCR4 is present on CD34+ hematopoetic progenitor cells and
its interaction with SDF-1 plays a pivotal role in the homing of
CD34+ cells in the bone marrow. Inhibition of the CXCR4-SDF1 axis
by AMD3100 releases CD34+ cells into the circulation, which can
then be collected easily by apheresis. Recently, a published report
demonstrated that large numbers of CD34+ cells were rapidly
mobilized in healthy volunteers following a single subcutaneous
injection of AMD3100.
[0183] The hematopoietic progenitor cells can be isolated fresh and
frozen mononuclear cells of peripheral blood, cord blood, and bone
marrow using its pan-hematopoietic antigen CD34 or by other methods
that are known to one skilled in the art. For example, antibodies
against CD34 can be used for immuno-isolating the CD34(+)
hematopoietic progenitor cells from the mononuclear cell fraction.
The anti-CD34 antibodies can be conjugated with fluorophores or to
magnetic beads for ease of separation by FACS or magnets
respectively.
[0184] Hematopoietic progenitor cells bearing the pan-hematopoietic
antigen CD34 can also be isolated by using taking advantage of the
cells ability to bind galactose-conjugated proteins. This
lectin-positive sub-population represents approximately 0.1 to 0.5%
of the total bone marrow cells, and contains 100% of the
hematopoietic progenitor cells. The galactose-binding lectin on
these cells is specific for this sugar. Additionally, highly
proliferative hematopoietic progenitor cells with very primitive
phenotypes, including a newly identified progenitor cell that
produces multiple lineages, express this lectin. (Pipia and Long,
Nature Biotechnology 15, 1007-1011 (1997)).
[0185] In vitro transfection of isolated hematopoietic progenitor
cells from a host facilitates targeted transfection of the miR-150
transgene into specific progenitor cells. Transfection of
progenitor cells can be accomplished by any transfection methods
known in the art, for example, calcium phosphate-mediated,
DEAE-Dextran-mediated, calcium alginate microbeads, cation
lipid-mediated, scrape-loading, and ballistic bombardment of
nucleic acid gold particles. In one embodiment, isolation and
culturing of progenitor cells is performed using the methods well
known in to those skilled in the art, e.g. as described in U.S.
Pat. Nos. 5,199,942, 5,474,687, 5,589,368, 5,612,211, 5,905,041,
6,355,237, and 7,345,025, which are hereby incorporated by
reference in their entirety. The identity of the isolated
hematopoietic progenitor cells can be confirmed by transglutaminase
expression in culture as described in WO2000/006766, which is also
hereby incorporated by reference in its entirety. After in vitro
transfection, the miR-150 transfection level can be monitored by
quantitative real-time PCR with specific primer pairs to the
pre-miR-150 and the mature miR-150. The transfected progenitor
cells carrying the transgene can be expanded in culture according
to methods described in U.S. Pat. Nos. 5,744,361, 5,905,041, and
6326198, which are hereby incorporated by reference in their
entirety. The expanded progenitor cells with the miR-150 transgene
can then be transplanted back into the original host.
Transplantation of progenitor cells are described in U.S. Pat. Nos.
5,817,773, 5,858,782, and U.S. Pat. App 10/730,334 and they are
hereby incorporated by reference in their entirety.
[0186] In one embodiment, the SEQ. ID. No. 1 (miR-150 gene) is
cloned into the MDH.xdna murine retroviral vector and miR-150
retroviral vectors can be transfected into isolated hematopoietic
progenitor cells. Forty-eight hours after transfection, total RNAs
were isolated and loaded onto a 10% denaturing polyacrylamide gel.
DNA oligo probes that were complementary to each of the selected
miRNAs were labeled and hybridized to the membrane to detect mature
miR-150s that can be efficiently processed (20- to 24-nt).
Constructs with high processing efficiency can be selected for bone
marrow transplantation.
Expression Vectors and Expression Systems for Expression
[0187] Isolated nucleic acid sequences that are at least 90%
identical to SEQ. ID. No. 1, 3 and 4 can be obtained using a number
of standard techniques. For example, the nucleic acids can be
chemically synthesized or recombinantly produced using methods
known in the art. In one embodiment, the nucleic acids are
chemically synthesized using appropriately protected ribonucleoside
phosphoramidites and a conventional DNA/RNA synthesizer. Commercial
suppliers of synthetic RNA molecules or synthesis reagents include,
e.g., Proligo (Hamburg, Germany), Dharmacon Research (Lafayette,
Colo., U.S.A.), Pierce Chemical (part of Perbio Science, Rockford,
Ill., U.S.A.), Glen Research (Sterling, Va., U.S.A.), ChemGenes
(Ashland, Mass., U.S.A.) and Cruachem (Glasgow, UK).
[0188] Alternatively, the nucleic acids and their complementary
strands can be synthesized as single strand DNA initially and then
subsequently anneal together to form duplex for cloning into
vectors for gene expression as described in Scheer M. et. al.
supra. Restriction enzyme sites can be designed and incorporated at
the ends of the eventual duplex to facilitate ligating the duplex
into a vector.
[0189] The human miR-150 stem loop (hsa-miR-150) is contained
within a 473 bp genomic fragment that includes the hairpin region
of hsa-miR-150 and .about.200 bp of flanking sequence on each side.
This genomic expression cassette can be PCR amplified from human
genomic DNA (Roche Applied Science) with primers containing 5'
linker sequences harboring relevant digestion sites (core primer
sequences: 5' CAGCATAGGGTGGAGTGGGT3' (Seq. ID. No. 5);
5'TACTTTGCGCATCACACAGA3' (SEQ. ID. No. 6).
[0190] Once ligated into a vector, the nucleic acid can be
subcloned into several expression vectors, such as a viral
expression vector or a mammalian expression vector by PCR cloning,
restriction digestion followed by ligation, or recombination
reaction such as those of the lambda phage-based site-specific
recombination using the GATEWAY.RTM. LR and BP CLONASE.TM. enzyme
mixtures. Subcloning should be unidirectional such that the 5'
transcription start nucleotide of the nuclei acid sequence is
downstream of the promoter in the expression vector. Alternatively,
when the nucleic acid sequence is cloned into pENTR/D-TOPO.RTM.,
pENTR/SD/D-TOPO.RTM. (directional entry vectors), or any of the
INVITROGEN's GATEWAY.RTM. Technology pENTR (entry) vectors, the
nucleic acid sequence can be transferred into the various
GATEWAY.RTM. expression vectors (destination) for protein
expression in host cells in one single recombination reaction. Some
of the GATEWAY.RTM. destination vectors are designed for the
constructions of baculovirus, adenovirus, adeno-associated virus
(AAV), retrovirus, and lentiviruses, which upon infecting their
respective host cells, facilitating ease of introducing the
transgene into the host cells. The GATEWAY.RTM. Technology uses
lambda phage-based site-specific recombination instead of
restriction endonuclease and ligase to insert a gene of interest
into an expression vector. The DNA recombination sequences (attL,
attR, attB, and attP) and the LR and BP CLONASE.TM. enzyme mixtures
that mediate the lambda recombination reactions are the foundation
of GATEWAY.RTM. Technology. Transferring a gene into a destination
vector is accomplished in just two steps: Step 1: Clone the nucleic
acid sequence of interest into an entry vector such as
pENTR/D-TOPO.RTM.. Step 2: Mix the entry clone containing the
nucleic acid sequence of interest in vitro with the appropriate
GATEWAY.RTM. expression vector (destination vector) and
GATEWAY.RTM. LR CLONASE.TM. enzyme mix. There are GATEWAY.RTM.
expression vectors for protein expression in E. coli, insect cells,
mammalian cells, and yeast. Site-specific recombination between the
att sites (attR.times.attL and attB.times.attP) generates an
expression vector and a by-product. The expression vector contains
the nucleic acid sequence of interest recombined into the
destination vector backbone. Following transformation and selection
in E. coli, the expression vector is ready to be used for
expression in the appropriate host.
[0191] The nucleic acid sequence of interest can be expressed from
recombinant circular or linear DNA vector using any suitable
promoter. Suitable promoters for expressing RNA from a vector
include, e.g., the U6 or H1 RNA pol III promoter sequences, or the
cytomegalovirus promoters. Selection of other suitable promoters is
within the skill in the art. The expression vector should have the
necessary 5' upstream and 3' downstream regulatory elements such as
promoter sequences, ribosome recognition and binding TATA box, and
3' UTR AAUAAA (SEQ. ID. No. 25) transcription termination sequence
for the efficient gene transcription and translation in its
respective host cell. The recombinant vectors can also comprise
inducible or regulatable promoters for expression of the nucleic
acid sequence of interest in hematopoietic progenitor cells. The
nucleic acids that are expressed from recombinant vectors can also
be delivered to, and expressed directly in, cells. In one
embodiment, the nucleic acids are expressed as RNA precursor
molecules from a single vector, and the precursor molecules are
processed into the functional miR gene product by a suitable
processing system, including, but not limited to, processing
systems extant within a cell. Other suitable processing systems
include, e.g., the in vitro Drosophila cell lysate system (e.g., as
described in U.S. Published Patent Application No. 2002/0086356 to
Tuschl et al., the entire disclosure of which is incorporated
herein by reference) and the E. coli RNAse III system (e.g., as
described in U.S. Published Patent Application No. 2004/0014113 to
Yang et al., the entire disclosure of which is incorporated herein
by reference).
[0192] Selection of vectors suitable for expressing the nucleic
acid sequence, methods for inserting nucleic acid sequences into
vector to express the gene products, and methods of delivering the
recombinant plasmid to the cells of interest are within the skill
in the art. See, for example, Zeng et al. (2002), Molecular Cell
9:1327-1333; Tuschl (2002), Nat. Biotechnol, 20:446-448;
Brummelkamp et al. (2002), Science 296:550-553; Miyagishi et al.
(2002), Nat. Biotechnol. 20:497-500; Paddison et al. (2002), Genes
Dev. 16:948-958; Lee et al. (2002), Nat. Biotechnol. 20:500-505;
and Paul et al. (2002), Nat. Biotechnol. 20:505-508, the entire
disclosures of which are incorporated herein by reference.
[0193] Examples of expression vectors for mammalian host cells
include but are not limited to the strong CMV promoter-based
pcDNA3.1 (INVITROGEN) and pCIneo vectors (Promega) for expression
in mammalian cell lines such as CHO, COS, HEK-293, Jurkat, and
MCF-7; replication incompetent adenoviral vector vectors pAdeno X,
pAdSF35, pLP-Adeno-X-CMV (Clontech), pAd/CMV/V5-DEST, pAd-DEST
vector (INVITROGEN) for adenovirus-mediated gene transfer and
expression in mammalian cells; pLNCX2, pLXSN, and pLAPSN retrovirus
vectors for use with the RETRO-X.TM. system from Clontech for
retroviral-mediated gene transfer and expression in mammalian
cells; pLENTI4/V5-DEST.TM., pLenti6/V5-DEST.TM., and
pLENTI6.2/V5-GW/lacZ (INVITROGEN) for lentivirus-mediated gene
transfer and expression in mammalian cells; adenovirus-associated
virus expression vectors such as pAAV-MCS, pAAV-IRES-hrGFP, and
pAAV-RC vector (Stratagene) for adeno-associated virus-mediated
gene transfer and expression in mammalian cells;
[0194] A simplified system for generating recombinant adenoviruses
is presented by He T C. et. al. Proc. Natl. Acad. Sci. USA
95:2509-2514, 1998. The gene of interest is first cloned into a
shuttle vector, e.g. pAdTrack-CMV. The resultant plasmid is
linearized by digesting with restriction endonuclease Pme I, and
subsequently cotransformed into E. coli. BJ5183 cells with an
adenoviral backbone plasmid, e.g. pAdEasy-1 of Stratagene's
AdEASY.TM. Adenoviral Vector System. Recombinant adenovirus vectors
are selected for kanamycin resistance, and recombination confirmed
by restriction endonuclease analyses. Finally, the linearized
recombinant plasmid is transfected into adenovirus packaging cell
lines, for example HEK 293 cells (E1-transformed human embryonic
kidney cells) or 911 (E1-transformed human embryonic retinal cells)
(Human Gene Therapy 7:215-222, 1996). Recombinant adenovirus are
generated within the HEK 293 cells.
[0195] In one embodiment, a recombinant lentivirus can be used for
the delivery and expression of a nucleic acid sequence that is at
least 90% identical to SEQ. ID. No. 1, 3 or 4 in either dividing
and non-dividing mammalian cells. The HIV-1 based lentivirus can
effectively transduce a broader host range than the Moloney
Leukemia Virus (MoMLV)-base retroviral systems. Preparation of the
recombinant lentivirus can be achieved using the
pLENTI4/V5-DEST.TM., pLFNTI6/V5-DEST.TM. or pLenti vectors together
with ViraPower.TM. Lentiviral Expression systems from
Invitrogen.
[0196] In one embodiment, a recombinant adeno-associated virus
(rAAV) vector can be used for the expression of a nucleic acid
sequence that is at least 90% identical to SEQ. ID. No. 1, 3 or 4.
Because AAV is non-pathogenic and does not illicit an immune
response, a multitude of pre-clinical studies have reported
excellent safety profiles. rAAVs are capable of transducing a broad
range of cell types and transduction is not dependent on active
host cell division. High titers, >10.sup.8 viral particle/ml,
are easily obtained in the supernatant and 10.sup.11-10.sup.12
viral particle/ml with further concentration. The transgene is
integrated into the host genome so expression is long term and
stable.
[0197] The use of alternative AAV serotypes other than AAV-2
(Davidson et al (2000), PNAS 97(7)3428-32; Passini et al (2003), J.
Virol 77(12):7034-40) has demonstrated different cell tropisms and
increased transduction capabilities. With respect to brain cancers,
the development of novel injection techniques into the brain,
specifically convection enhanced delivery (CED; Bobo et al (1994),
PNAS 91(6):2076-80; Nguyen et al (2001), Neuroreport 12(9):1961-4),
has significantly enhanced the ability to transduce large areas of
the brain with an AAV vector.
[0198] Large scale preparation of AAV vectors is made by a
three-plasmid cotransfection of a packaging cell line: AAV vector
carrying the chimeric DNA coding sequence, AAV RC vector containing
AAV rep and cap genes, and adenovirus helper plasmid pDF6, into
50.times.150 mm plates of subconfluent 293 cells. Cells are
harvested three days after transfection, and viruses are released
by three freeze-thaw cycles or by sonication.
[0199] AAV vectors are then purified by two different methods
depending on the serotype of the vector. AAV2 vector is purified by
the single-step gravity-flow column purification method based on
its affinity for heparin (Auricchio, A., et. al., 2001, Human Gene
therapy 12; 71-6; Summerford, C. and R. Samulski, 1998, J. Virol.
72:1438-45; Summerford, C. and R. Samulski, 1999, Nat. Med. 5:
587-88). AAV2/1 and AAV2/5 vectors are currently purified by three
sequential CsCl gradients. Delivery vectors can also included but
are not limited to replication-defective adenoviral vectors,
cationic liposomes and protein-cationic peptides. For example, one
study reports a system to deliver DNA in vitro by covalently
attaching the surfactant associated protein B (SP-B) to a 10 kDa
poly-lysine. See, Baatz, J., et al., PNAS USA, 91:2547-2551 (1994).
See, e.g., Longmuir, et al., 1992 ASBMB/Biophysical Society
abstract; Longmuir, et al., 1993 Biophysical Society abstract.
Therapeutic Uses and Administration
[0200] In one embodiment, a nucleic acid or vector administered to
the host cells comprise a non-cationic lipid for cytoplasmic and/or
nuclear delivery, wherein the nucleic acid or vector is stable and
is used in biological extracellular fluids typically found in
animals, particularly blood serum.
[0201] Liposomes, spherical, self-enclosed vesicles composed of
amphipathic lipids, have been widely studied and are employed as
vectors for in vivo administration of therapeutic agents. In
particular, the so-called long circulating liposomes formulations
which avoid uptake by the organs of the mononuclear phagocyte
system, primarily the liver and spleen, have found commercial
applicability. Such long-circulating liposomes include a surface
coat of flexible water soluble polymer chains, which act to prevent
interaction between the liposome and the plasma components which
play a role in liposome uptake. Alternatively, hyaluronan has been
used as a surface coating to maintain long circulation.
[0202] In one embodiment, the liposome encapsulate the nucleic acid
sequences, vectors or even the viral particles. In one embodiment,
the nucleic acid sequences or vectors are condensed with a cationic
polymer, e.g., PEI, polyamine spermidine, and spermine, or a
cationic peptide, e.g., protamine and poly-lysine, and encapsulated
in the lipid particle. The liposomes can comprise multiple layers
assembled in a step-wise fashion.
[0203] Lipid materials well known and routinely utilized in the art
to produce liposomes. Lipids may include relatively rigid
varieties, such as sphingomyelin, or fluid types, such as
phospholipids having unsaturated acyl chains. "Phospholipid" refers
to any one phospholipid or combination of phospholipids capable of
forming liposomes. Phosphatidylcholines (PC), including those
obtained from egg, soy beans or other plant sources or those that
are partially or wholly synthetic, or of variable lipid chain
length and unsaturation are suitable for use in the present
invention. Synthetic, semisynthetic and natural product
phosphatidylcholines including, but not limited to,
distearoylphosphatidylcholine (DSPC), hydrogenated soy
phosphatidylcholine (HSPC), soy phosphatidylcholine (soy PC), egg
phosphatidylcholine (egg PC), hydrogenated egg phosphatidylcholine
(HEPC), dipalmitoylphosphatidylcholine (DPPC) and
dimyristoylphosphatidylcholine (DMPC) are suitable
phosphatidylcholines for use in this invention. All of these
phospholipids are commercially available. Further,
phosphatidylglycerols (PG) and phosphatic acid (PA) are also
suitable phospholipids for use in the present invention and
include, but are not limited to, dimyristoylphosphatidylglycerol
(DMPG), dilaurylphosphatidylglycerol (DLPG),
dipalmitoylphosphatidylglycerol (DPPG),
distearoylphosphatidylglycerol (DSPG) dimyristoylphosphatidic acid
(DMPA), distearoylphosphatidic acid (DSPA), dilaurylphosphatidic
acid (DLPA), and dipalmitoylphosphatidic acid (DPPA).
Distearoylphosphatidylglycerol (DSPG) is the preferred negatively
charged lipid when used in formulations. Other suitable
phospholipids include phosphatidylethanolamines,
phosphatidylinositols, sphingomyelins, and phosphatidic acids
containing lauric, myristic, stearoyl, and palmitic acid chains.
For the purpose of stabilizing the lipid membrane, it is preferred
to add an additional lipid component, such as cholesterol.
Preferred lipids for producing liposomes according to the invention
include phosphatidylethanolamine (PE) and phosphatidylcholine (PC)
in further combination with cholesterol (CH). According to one
embodiment of the invention, a combination of lipids and
cholesterol for producing the liposomes of the invention comprise a
PE:PC:Chol molar ratio of 3:1:1. Further, incorporation of
polyethylene glycol (PEG) containing phospholipids is also
contemplated by the present invention.
[0204] In addition, in order to prevent the uptake of the liposomes
into the cellular endothelial systems and enhance the uptake of the
liposomes into the tissue of interest, the outer surface of the
liposomes may be modified with a long-circulating agent. The
modification of the liposomes with a hydrophilic polymer as the
long-circulating agent is known to enable to prolong the half-life
of the liposomes in the blood
[0205] Liposomes encapsulating the nucleic acid sequences described
herein can be obtained by any method known to the skilled artisan.
For example, the liposome preparation of the present invention can
be produced by reverse phase evaporation (REV) method (see U.S.
Pat. No. 4,235,871), infusion procedures, or detergent dilution. A
review of these and other methods for producing liposomes may be
found in the text Liposomes, Marc Ostro, ed., Marcel Dekker, Inc.,
New York, 1983, Chapter 1. See also Szoka Jr. et al., (1980, Ann.
Rev. Biophys. Bioeng., 9:467).
[0206] The use of an therapeutically effective amount of the
nucleic acid sequences or vectors disclosed herein for the
treatment of thrombocytopenia and anemia should preferably include
but is not limited to a composition of the nucleic acid segments in
lactated Ringer's solution and the composition is sterile. Lactated
Ringer's solution is a solution that is isotonic with blood and
intended for intravenous administration. Include are antioxidants,
buffers, antibiotics and solutes that render the compositions
substantially isotonic with the blood of an intended recipient. In
another embodiment, the composition comprise gene delivery vectors
described herein. In another embodiment, the composition also
include water, polyols, glycerine and vegetable oils, and nutrients
for cells, for example. Compositions adapted for parenteral
administration can be presented in unit-dose or multi-dose
containers, in a pharmaceutically acceptable dosage form. Such
dosage forms, along with methods for their preparation, are known
in the pharmaceutical and cosmetic art. Harry's Cosmeticology
(Chemical Publishing, 7th ed. 1982); Remington's Pharmaceutical
Sciences (Mack Publishing Co., 18th ed. 1990).
[0207] In one embodiment, dosage forms include pharmaceutically
acceptable carriers that are inherently nontoxic and
nontherapeutic. Examples of such carriers include ion exchangers,
alumina, aluminum stearate, lecithin, serum proteins, such as human
serum albumin, buffer substances such as phosphates, glycine,
sorbic acid, potassium sorbate, partial glyceride mixtures of
saturated vegetable fatty acids, water, salts, or electrolytes such
as protamine sulfate, disodium hydrogen phosphate, potassium
hydrogen phosphate, sodium chloride, zinc salts, colloidal silica,
magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based
substances, and polyethylene glycol.
[0208] In one embodiment, other ingredients can be added, including
antioxidants, e.g., ascorbic acid; low molecular weight (less than
about ten residues) polypeptides, e.g., polyarginine or
tripeptides; proteins, such as serum albumin, gelatin, or
immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone;
amino acids, such as glycine, glutamic acid, aspartic acid, or
arginine; monosaccharides, disaccharides, and other carbohydrates
including cellulose or its derivatives, glucose, mannose, or
dextrins; chelating agents such as EDTA; and sugar alcohols such as
mannitol or sorbitol.
[0209] In one embodiment, the administration of the nucleic acid
segments or gene delivery vectors disclosed herein are by any
suitable route, and means, for example, parenterally, intravenous,
intra-arterial, intracranial, intracerobrospinal, intratumoral,
peritoneal, by injection, by catheter, by implantation with or
without a matrix or gel material, or by gradual delivery device. In
one embodiment, the nucleic acid segments or gene delivery vectors
described herein can be administered directly by injection.
[0210] The therapeutically effective amount amounts to be
administered will depend on the severity of the condition and
individual patient parameters including age, physical condition,
size, weight and concurrent treatment. These factors are well known
to those of ordinary skill in the art and can be addressed with no
more than routine experimentation. It is preferred generally that a
maximum dose be used, that is, the highest safe dose according to
sound medical judgment. It will be understood by those of ordinary
skill in the art; however, that a lower dose or tolerable dose may
be administered for medical reasons, psychological reasons or for
virtually any other reason.
[0211] This invention is further illustrated by the following
example which should not be construed as limiting. The contents of
all references cited throughout this application, as well as the
figures and table are incorporated herein by reference.
Examples
Materials and Methods
[0212] MiRNA expression profiling and data analysis--miRNA
expression profiling was performed using the plate capture method
unless otherwise stated. 96-well PCR plates with N-oxysuccinimide
surface (DNA-BIND plates, Corning Costar) were coated at room
temperature for 1 hour with 5 .mu.M mixture of 5' amino-antisense
oligonucleotides (see Table 4) at 20 .mu.l per well according to
manufacturer's protocol. Coated plates were successively washed
with (100 mM Tris-HCl, pH8.0, 150 mM NaCl, 1 mM EDTA) and (10 mM
Tris-HCl, pH 8.0, 1 mM EDTA). Total RNA (10 ng or higher) was
diluted to 20 .mu.l in 50 mM Tris-HCl, pH 8.0, 1 M NaCl, 1 mM EDTA,
1.times.RNAsecure (Ambion), containing pre-control synthetic miRNA
mixture at the ratio previously described (1). miRNAs were captured
in the coated wells by denaturing at 80.degree. C. for 5 minutes
and gradually cooling to room temperature in 1.5 hours in a PCR
machine, followed by three 2.times.SSC washes. 3' adaptor ligation
and 5' adaptor ligations were carried out as described (1) in 20
.mu.l reaction volumes, with four 2.times.SSC washes after each
ligation. Ligated miRNA were denatured for 5 minutes at 80.degree.
C. in 20 .mu.l water with 2 .mu.M adaptor-specific RT primer,
chilled on ice, and reverse transcribed as described (1). RT
products were denatured at 95.degree. C. for 5 minutes before 2
rounds of PCR amplification with described conditions (1), for 26
and 27 cycles respectively, to incorporate biotin labels for low
input RNA profiling. Labeled miRNAs were hybridized to a bead-based
detection platform (1), with updated detection probes (Table 5).
Median fluorescence intensities were quantitated on a Luminex 100S
machine (Luminex Corp).
[0213] Data were normalized as described (1) with modifications.
Average readings from 5 water-only labeled samples were used for
probe-specific background subtraction.
[0214] Linear normalization among different bead sets for the same
sample was performed using readings from 2 post-control probes with
equal contribution. Sample normalization was subsequently carried
out assuming equal total fluorescence readings. To identify
markers, all ERY samples were compared to all MEGA samples, with
median-based t-test and 50,000 permutations, using the Comparative
Marker Selection module in GENEPATTERN (2).
[0215] Cell sorting and flow cytometry--Human umbilical cord blood
was harvested at Brigham and Women's Hospital with informed patient
consent under an IRB approved protocol. Adult human bone marrow
cells were obtained from AllCells, LLC. Mononuclear cells were
purified by Ficoll Hypaque sedimentation. Lineage depletion was
performed using antibodies against CD2, CD3, CD4, CD5, CD8, CD1 1b,
CD14C, CD19, and CD56 with a magnetic column (Miltenyi Biotec).
Populations were defined as follows: MEP(CD34+CD38iL-3Ra-CD45RA-),
ERY1 (CD34+CD71+GlyA-), ERY2 (CD34-CD71+GlyA-), ERY3
(CD34-CD71+GlyA+). Megakaryocytes were purified without lineage
depletion according to the following immunophenotypes: MEGA1
(CD34+CD6 1+CD4 1+CD45-), MEGA2 (CD34-CD61+CD41+CD45-). Adult human
bone marrow cells were similarly sorted according to
CD34-CD61+CD41+ and CD34-CD71+GlyA+. Sorting was performed with a
Vantage SE Diva or with an Aria (BD Biosciences). RNA was extracted
using TRIZOL (INVITROGEN).
[0216] For the in vitro human primary culture experiment,
approximately 500,000 cells were stained with CD41-FITC, Ter119-PE
and CD71-PE-Cy5 antibodies for 15 minutes on ice and washed twice
before flow cytometry. For analysis of transplant recipients,
murine bone marrow cells were labeled with CD41-PE and Ter119-APC,
or Ter119-APC and CD71-PE. Peripheral blood cells were harvested
into 0.38% sodium citrate and stained with CD41-PE.
[0217] Mouse MEPs were purified as described in (3). Briefly, bone
marrow cells were harvested from 8- to 10-week old C57Bl6/J mice
and stained with an antibody cocktail containing biotinylated
lineage markers including Ter119, CD3, CD4, CD8, CD 1 1b/Mac-1 Gr-1
and B220, and followed by staining with a second antibody cocktail
containing streptavidin-PerCP, Sca-PE, cKit-APC, CD16/32 PE-Cy7 and
CD34-FITC. MEPs are defined as the
Lin-cKit+Sca-CD34-CD16/32-population. Antibodies used for cell
surface markers are found in Table 2.
[0218] Constructs--Expression vectors for hsa-miR-150 contain a 473
bp genomic fragment that includes the hairpin region of hsa-miR-150
and .about.200 bp of flanking sequence on each side. This genomic
expression cassette was PCR amplified from human genomic DNA (Roche
Applied Science) with primers containing 5' linker sequences
harboring relevant digestion sites (core primer sequences:
5'CAGCATAGGGTGGAGTGGGT3' (SEQ. ID. No. 5); 5'TACTTTGCGCATCACACAGA3'
(SEQ. ID. No. 6)). For the human CD34+ primary culture experiment,
the lenti-viral vector pLKO. 1 (obtained from The RNAi Consortium,
Broad Institute) was used, with the miR-150 expression cassette, or
an shRNA against luciferase (shLuc), cloned into the AgeI and EcoRI
sites. hsa-miR-15b-16-2 was similarly cloned with a genomic DNA
fragment through PCR amplification (core primer sequences:
5'TITCCTCAAAACAGGAAGG3' (SEQ. ID. No. 7); 5'CCACCAAGTAAGTCATTTTC3'
(SEQ. ID. No. 8)). For expression in cell lines, the miR-150
expression cassette, or EGFP coding sequence, was cloned into the
pMSCV-puro vector through the BglII and MluI sites. For in vivo
transplantation assays, the pMSCV-puro vector was substituted with
pMSCV-EGFP, in which the EGFP coding sequence replaced that of the
puromycin resistance gene in pMSCV-puro.
[0219] Mutant miR-150 constructs were created by PCR-mediated
site-directed mutagenesis. Mutations were introduced into the 5'
seed region of mature hsa-miR-150, as well as into the opposite arm
of the hairpin to maintain overall hairpin structure. Primers used
are listed below:
TABLE-US-00001 (SEQ. ID. No. 9) 5'
CCCCATGGCCCTGTCTGGGAACCCTTGTACCAGTG3' (SEQ. ID. No. 10) 5'
CACTGGTACAAGGGTTCCCAGACAGGGCCATGGGG3' (SEQ. ID. No. 11) 5'
CCCTGGTACAGGCCTCCCGGACAGGGACCTG3' (SEQ. ID. No. 12) 5'
CAGGTCCCTGTCCGGGAGGCCTGTACCAGGG3'.
[0220] The MYB cDNA clone, containing only the coding sequence and
Kozak sequence, was obtained from Invitrogen (Ultimate ORF
collection) in the form of a Gateway entry vector. This clone, as
well as a Gateway entry clone without insert (vector control), were
recombined into pLenti6.2/V5DEST vector using LR recombination
reactions (Invitrogen).
[0221] MYB 3'UTR luciferase reporter was created by inserting human
MYB 3' UTR (according to RefSeq NM.sub.--005375) into the XhoI and
NotI sites in the psiCHECK2 vector (Promega), downstream of the
renilla luciferase coding sequence. MYB 3'UTR was amplified from
human genomic DNA with the following primers:
TABLE-US-00002 (SEQ. ID. No. 13)
5'TAACTCGAGACATTTCCAGAAAAGCATTATG3', and (SEQ. ID. No. 14)
5'ATAGCGGCCGCAGGTAAAATAAGGGCACATC3'.
[0222] Mutations of putative miR-150 binding sites were created by
PCR-mediated site-directed mutagenesis. Primers used are listed
below.
TABLE-US-00003 (SEQ. ID. No. 15) Site 1:
5'ACTTTTCATGAATCCCAGAAGAACCTAT3' (SEQ. ID. No. 16)
5'ATAGGTTCTTCTGGGATTCATGAAAAGT3' (SEQ. ID. No. 17) Site 2:
5'TGAAAACTTGTTTCCCAGACTCTGCATT3' (SEQ. ID. No. 18)
5'AATGCAGAGTCTGGGAAACAAGTTTTCA3' (SEQ. ID. No. 19) Site 3:
5'TGCACTTCTTTTTTCCCAGATGTGTGTTGT3' (SEQ. ID. No. 20) 5'ACAACACACAT
CT GGGAAAAAAGAAGT GCA3' (SEQ. ID. No. 21) Site 4:
5'CTGTTTTATAATTTCCCAGTTCTGCATTTG3' (SEQ. ID. No. 22) 5'CAAAT
GCAGAAC T GGGAAAT TATAAAACAG3'
[0223] Short hairpin RNAs against human MYB were obtained from The
RNAi Consortium (world wide web "period" broad "period" mit
"period" edu "forward slash" genome "underscore" bio "forward
slash" trc "forward slash"). The IDs of the shMYB-1 and shMYB-2
clones are TRCN0000040058 and TRCN0000009853.
[0224] Quantitative RT-PCR-Quantitative RT-PCR primers and probes
were all obtained from Applied Biosystems. Reverse transcription
reactions were performed following the manufacturer's protocol with
minor modifications. Briefly, 1 ng to 10 ng of total RNA were
reverse transcribed using the MultiScribe cDNA synthesis system
(Applied Biosystems) in 5 .mu.L volume with either miRNA gene
specific RT primers, or with 6.25 ng random primers (Invitrogen).
Duplicate or triplicate RT reactions were performed for each sample
and each RT primer. RT products were diluted 2.5 fold before PCR.
PCR reactions were performed in duplicate for each RT product,
following the manufacturer's protocol and using assays from Applied
Biosystems on an ABI HT7900 real time PCR machine. Reactions for
eukaryotic 18S ribosomal RNA and messenger RNAs were performed with
random-primer-based RT products, whereas reactions for miRNAs used
corresponding gene-specific RT products. Threshold cycles (using a
manual cutoff of 0.2) or genes of interest were normalized by Ct
values of corresponding 1 8S rRNA reactions. .DELTA.Ct values (Ct
of 1 8S minus Ct of gene of interest) were used unless specified
otherwise. Quantitative RT-PCR assays used in this study are found
in Table 1.
[0225] In vitro primary culture of human CD34+ cells-Cryopreserved
human adult bone marrow CD34+ cells were obtained from Cambrex
(Poietics; Cambrex). Cells were cultured in Serum Free Expansion
Medium (SFEM, Stem Cell Technologies) supplemented with 100 U/mL
penicillin/streptomycin, 2 mM glutamine, and 40 .mu.g/mL lipids
(SIGMA ALDRICH). Erythroid and megakaryocytic differentiation were
supported in a single liquid culture, similarly as described (4),
in the presence of 50 ng/mL TPO, 100 ng/mL SCF, 10 ng/mL IL-3, 10
ng/mL IL-6, and 0.5 U/mL EPO. The concentration of EPO was
increased to 3 IU/mL on day 7. Cells were harvested for flow
cytometry following 10 days of liquid culture. Lentiviral infection
was performed starting one day after thawing cells. Where
indicated, cDNA construct and miRNA construct were infected on
consecutive days. Cells were selected with 2 .mu.g/mL puromycin or
3 .mu.g/mL blasticidin one day after infection.
[0226] Murine bone marrow transplant-All mice were purchased from
the Jackson Laboratory. Murine bone marrow transplant was performed
similarly as previously described (5), and approved by the MGH
Subcommittee on Research Animal Care. Donor C57Bl6/J mice (.about.8
weeks) were primed with 150 mg/kg SCF for four days. Bone marrow
cells were purified by Ficoll (GE Healthcare) density gradient
centrifugation, following the manufacturer's protocol. Cells were
transduced with empty vector or miR-150 retrovirus in X-VIVO 15
medium (Biowhittaker) supplemented with 100 ng/mL SCF, 50 ng/mL
TPO, 50 ng/mL Flt3 ligand and 20 ng/mL IL3 by centrifugation onto
plates coated with retronectin (TAKARA). Lethally irradiated (9.5
Gy) recipient mice were transplanted with 2.5-4 million cells the
day after infection. Hematopoeitic recovery was monitored by
complete blood count. Bone marrow cells of 7 pairs of recipients
were analyzed at 5 to 8 weeks post-transplantation respectively.
Platelets were analyzed 7-weeks post-transplantation.
[0227] Cell culture--K562 and 293T cells were obtained from ATCC,
and were cultured according to ATCC instructions.
[0228] Mouse bone marrow cells were treated with antagomir (50
.mu.g/ml) or PBS for three days in X-VIVO 15 medium (Biowhittaker)
supplemented with 50 ng/mL SCF, 50 ng/mL TPO, 50 ng/mL Flt3 ligand
and 20 ng/mL IL3. Cells were then harvested for RNA analysis.
[0229] Oligonucleotides and antagomirs-DNA oligonucleotides were
synthesized by IDT Technology. RNA oligonucleotides, including
antagomirs and DNA-RNA hybrids, were synthesized by Dharmacon.
Antagomir stock solution was prepared in PBS.
TABLE-US-00004 (SEQ. ID. No. 23) Antagomir-150: 5'
mC(*)mA(*)mCmUmGmGmUmAmCmAmAmGmGmGmUmUmGmGmG(*)mA (*)mG(*)mA
(*)(3'-Chl) 3'. (SEQ. ID. No. 24) Antagomir-scrambled:
5'mC(*)mU(*)mCmGmCmGmUmAmGmA mAmGmAmGmUmAmGmGmU(*)mG(*)mG(*)mA(*)
(3'-Chl) 3'. (mN: 2'OMe base; *: phosphorothioate linkage; Chl:
cholesterol).
[0230] Colony assay--Megakaryocyte colony assay was performed using
the MegaCult-C kit (Stem Cell Technology) according to the
manufacturer's protocol. Bone marrow cells from recipient mice 7 to
10 weeks after transplantation were sorted into GFP- and GFP+
populations. Two recipient mice were analyzed for each construct,
and each population of cells was assayed in duplicates with 100,000
sorted bone marrow cells per well. Cultures were maintained for 8
days before stained for acetylcholinesterase activity and scored.
For antagomir treatment, 1000 LKS cells or 4000 MEPs were
FACS-sorted and assayed in the presence of antagomir (50 .mu.g/ml)
or PBS and maintained in culture for 11 days before staining and
scoring. In all cases, a colony with .gtoreq.3
acetylcholinesterase-positive cells was scored as a megakaryocyte
colony.
[0231] For erythroid colony assay, 5FU primed wild type C57Bl6/J
marrow was transduced as described above. Forty-eight hours after
viral transduction, 30,000 GFP+ cells were FACS-sorted and plated
into methylcellulose (StemCell Technologies, M3334) which only
contains EPO.
[0232] Anemic response--Phenylhydrazine hydrochloride (Sigma)
solution in PBS was injected intraperitoneally into 10- to 12-week
wild type C57Bl6/J mouse (60 mg/kg body weight) on each of days 0,
1, and 2. On the 3rd day, mice were euthanized by CO2 inhalation
and bone marrow was harvested and stained with a lineage marker
antibody cocktail as described in cell sorting and flow cytometry.
Lineage negative cells were FACS sorted into TRIZOL reagent for RNA
preparation.
[0233] Western blot analysis--Western blot analysis was performed
as previously described (6). MYB antibody (clone 1-1) was from
Upstate Biotechnology. Beta tubulin antibody (ab6046) was from
Abcam.
[0234] Luciferase reporter assay--293T cells were plated in 96 well
plates at 5000 cells per well the day before transfection.
Transfection was carried out in 8 replicates using FuGENE 6
(Roche), with 100 ng of plasmid mixture (90 ng of expression vector
and 10 ng of reporter vector in the psiCHECK2 backbone). Luciferase
assays for both firefly and renilla luciferase were performed 2
days after transfection, using the Dual-Glo Luciferase assay kit
(Promega). Luminescence was quantitated on a Tecan Spectrafluor
Plus machine. Renilla luciferase readings were normalized against
the firefly luciferase activity in the corresponding well.
[0235] Statistical Analysis--Student's t-test (2 tailed, unequal
variance) was used for statistical analysis on experiments, unless
otherwise specified.
Example 1
miRNA Expression In Hematopoietic Progenitor Cells
[0236] Mammalian developmental cell fate can be guided at least in
part by different mechanism of gene regulation, such as by miRNAs.
These recently discovered .about.22 nt non-coding RNAs negatively
regulate the expression of target proteins either by inhibiting
translation of their cognate mRNAs, or by inducing mRNA
degradation, primarily through sites in the 3'UTR (see review (6)).
Previous miRNA expression patterns encode developmental history
supports a role of miRNAs in lineage specification (7). Here, MEP
differentiation was used as a model system to test that miRNA can
regulate cell fate, starting with the profiling of the expression
of miRNAs in MEPs, erythroid and megakaryocytic primary cells.
[0237] Unfortunately, the small number of precursor cells
obtainable from human donors has precluded a thorough analysis of
miRNA expression in hematopoiesis (and other systems) using
conventional miRNA profiling methods, which generally require
either large amounts of input RNA, or are not amenable to
genome-wide, high throughput applications. To address this
technical challenge, a method was developed in which mature miRNAs
are captured in 96-well plates using immobilized 5'-amino-modified
oligonucleotides complementary to the mature miRNA sequence of more
than 300 human miRNAs (from the miRBASE (8) release 7.0). This
plate-based capture obviates the need for gel-purification of small
RNAs which, in addition to being labor-intensive, results in
significant loss of input miRNAs. The captured miRNAs were ligated
with adaptors on 3' and 5' ends successively, reverse transcribed,
and amplified via PCR (FIG. 1A). The biotinylated PCR products were
then detected by hybridization to fluorescent beads coupled to
capture oligonucleotides complementary to the mature miRNA
sequence. The beads were then analyzed by flow cytometry, where the
color of the bead indicates the identity of the miRNA and the
phycoerythrin channel indicates the abundance of that particular
miRNA (7). In contrast to previously reported method (7) that
required .about.10 .mu.g of input RNA, the present method yields
similarly informative results with as little as 10 ng of total RNA
(FIG. 5). FIG. 5A shows the reproducibility performance of the
plate capture method of miRNA labeling. Two experiments of miRNA
profiling with the plate capture method were performed on total RNA
from MCF-7, 293T or K562 cells. Data were normalized and log
2-transformed. Data from experiment 1 were plotted against data
from experiment 2. Each dot represents the reading of one miRNA in
one sample. FIG. 5B shows data that were normalized and log
2-transformed. The differences of log 2-transformed data between
MCF-7 and 293T cells, which reflect the fold change, were plotted
to compare the two labeling methods. Each dot represents one miRNA.
Note that most dots are close to the diagonal, indicating the two
labeling methods captured similar results.
[0238] With a suitable miRNA profiling method in hand, the miRNA
expression pattern in MEPs and early megakaryocytic and erythroid
populations obtained from FACS-sorted human umbilical cord blood
samples were examined. Using well-established surface markers, 6
populations of cells were purified, and them are referred to as
MEP(CD34+,CD38+,IL-3R.alpha.-,CD45RA-), MEGA1
(CD34+,CD41+,CD61+,CD45-), MEGA2 (CD34-,CD41+,CD61+,CD45-), ERY1
(CD34+,CD71+,GlyA-), ERY2 (CD34-,CD71+,GlyA-) and ERY3
(CD34-,CD71+,GlyA+). These 6 populations thus capture the
bifurcation of the megakaryocytic and erythroid lineages with fine
granularity (FIG. 1C).
[0239] Profiling of 320 miRNAs was performed to identify those most
differentially expressed across the megakaryocytic and erythroid
populations. The profiling result (FIG. 1B, Table 6) captured and
extended known miRNA expression patterns. For example, miR-451 and
miR-144 were highly expressed in CD71+GlyA+erythrocytes, and
miR-222 was down-regulated during erythropoiesis (9, 10) (FIG. 1B).
Among all miRNAs, differential analysis (Table 3) identified
miR-150 with the most divergent expression between early
megakaryocytic and erythroid cells, being expressed >15-fold
higher in megakaryocytes (FIG. 1C). Quantitative RT-PCR analysis in
sorted umbilical cord blood cells confirmed miR-150 as being highly
expressed in megakaryocytes, weakly expressed in erythrocytes and
moderately expressed in MEPs (FIG. 1D, FIG. 16). Similarly, miR-150
was expressed more highly in CD41+CD61+ megakaryocytes than in
CD71+GlyA+ erythrocytes in human adult bone marrow (FIG. 6B).
Example 2
Function of miR-150 in Differentiation of Progenitor Cells
[0240] While high level expression of miR-150 was observed in the
megakaryocytic lineage, it is conceivable that it may not play a
functional role in the specification of megakaryocytes versus
erythrocytes. Arguing for its functional importance is its
exquisite sequence conservation across organisms with functional
erythrocytic and thrombocytic systems, exhibiting identical
sequence in the 5' seed region that mediates target recognition
(FIG. 7). To assess a potential causal role of miR-150 in the
specification of megakaryocytes versus erythrocytes, a series of
gain- and loss-of-function experiments were performed.
[0241] First, a bi-lineage primary cell culture was used, in which
human CD34+ hematopoietic progenitor cells isolated from adult
human bone marrow, when cultured in the presence of thrombopoietin
and erythropoietin, differentiate along the megakaryocytic and
erythroid lineages in vitro. This system allowed the quantitative
perturbation in the balance of megakaryocytic and erythroid
development from progenitor cells. CD34+ cells were transfected
with a lentiviral construct harboring miR-150, resulting in a
physiological level of miR-150 expression that is similar to that
observed in primary megakaryocytes (FIG. 8).
[0242] The function of miR-150 was assayed in an in vitro primary
culture. CD34+ hematopoietic progenitors derived from human adult
bone marrow cells were transduced with constructs expressing a
control hairpin (shLuc), miR-150, a mutant miR-150 or miR-15b-16-2.
The culture was analyzed after 10 days of differentiation, using
flow cytometry with lineage markers CD41 (megakaryocytic) and GlyA
(erythroid). Transduced cells were allowed to differentiate.
Megakaryocytes were then enumerated by flow cytometry measuring the
CD41+GlyA-population. Compared to CD34+ cells transduced with a
control vector (shLuc, expressing a short hairpin RNA against
luciferase), mutant miR-150, or an irrelevant miRNA construct
(miR-15b-16-2), the miR-150 expressing cells yielded an average of
8-fold enrichment of megakaryocytes (FIG. 2A, 2B). This result
indicates that miR-150 shifts the balance of
megakaryocytic-erythroid differentiation towards megakaryocytes,
and further indicates its role in governing the fate of MEPs.
Example 3
Function of miR-150 in In Vivo Differentiation of Progenitor
Cells
[0243] Having established a functionally important role of miR-150
in a human in vitro model of MEP differentiation, the functions of
miR-150 in vivo were examined to address whether miR-150 inhibits
the erythroid lineage, promotes the megakaryocytic lineage, or
both. To this end, a murine bone marrow transplantation model was
used, in which stem/progenitor-cell-enriched bone marrow cells from
donor mice were transduced with either miR-150 retrovirus or
control virus at low titer. The vectors carry a GFP marker, thus
labeling transduced cells and cells derived from them with green
fluorescence. The mixture of transduced and non-transduced donor
cells was transplanted into lethally irradiated recipients. Bone
marrow and peripheral blood of recipients were analyzed 5 to 8
weeks post transplantation, when the hematopoietic system had
largely recovered in the hosts. Both viral vectors carry GFP as a
marker, allowed the distinguishing between donor-derived cells that
were transduced from those that were not (FIG. 9).
[0244] miR-150 was expressed from a retroviral vector with a GFP
marker. This construct, or a control vector, was assayed by murine
bone marrow transplant. Recipient mice were analyzed 5 to 8 weeks
post-transplantation on transduced (GFP+) and non-transduced (GFP-)
cells. Flow cytometry was used to assay the bone marrow cells with
megakaryocyte-(CD41) and erythrocyte-(Ter119) specific markers.
Strikingly, compared to either non-transduced (GFP-) cells in
miR-150 recipients, or vector control recipient mice, miR-150
transduced (GFP+) bone marrow cells exhibited a dramatic
(>15-fold on average) expansion of megakaryocytes (CD41+Ter119-)
in relation to all transduced cells in the bone marrow (FIG. 2C,
2E, 10). Recipient bone marrow cells were FACS sorted into GFP+ and
GFP- populations, and measured for PF4 expression using
quantitative RT-PCR. Each pair of bars represents data from one
recipient mouse. It was observed that a strong elevation in the
expression of the megakaryocyte-specific gene PF4 (11) occurred in
miR-150 transduced bone marrow cells (FIG. 2F). In addition, the
circulating platelets were analyzed in the peripheral blood of
recipient animals 7-week post-transplantation. The ratio of GFP+
platelet percentage to the percentage of GFP+ bone marrow cells was
plotted to reflect the thrombocytogenic potential of bone marrow
cells. n=5. There was a consistent 2- to 14-fold enrichment in GFP+
circulating platelets in miR-150 animals compared to control vector
recipients (FIG. 2G, 11). These results proved that miR-150
expression led to a bona fide increase in bone marrow
megakaryocytes that were competent to produce mature platelets in
circulation.
[0245] In contrast, an over 60% decrease in GFP+ erythrocytes
(Ter119+CD41-) was observed, again in relation to all GFP+ cells in
the bone marrow (FIG. 2D, 2E). Importantly, the absolute numbers of
GFP+ megakaryocytes in the bone marrow increased, whereas that of
erythrocytes decreased in the presence of miR-150 expression (FIG.
12). Bone marrow cells with CD71 and Ter 19 were examined, which
distinguish different stages of murine erythroid differentiation
(12). The R1 to R4 gates on CD71/Ter119 plot show that miR-150
expressing cells displayed a strong shift toward an earlier
(immature) erythroid state, compared to controls (FIG. 2H, 2I, 2J).
The percentage of R1 population among all erythrocytes (sum of R1
to R4) was used to derive a ratio between GFP+ and GFP- population
within the same recipient mouse. n=7. P<0.002. Specifically,
miR-150 expression led to an average of 8-fold increase in the
immature R1 population, and a more than 60% decrease in the late R4
stage. These experiments indicate that ectopic miR-150 expression
induces a blockage in the earliest definable stage of murine adult
erythropoiesis, in addition to causing a significant reduction in
the total erythroid population.
[0246] The megakaryocyte-promoting effect of miR-150 could be due
to its effect on MEP commitment, or simply an effect on
post-commitment megakaryocytic proliferation or survival. To
address this, colony formation assay was used to quantify the
megakaryocytic potential of progenitor cells at the single cell
level. Erythroid colony formation assays were performed with 30,000
transduced bone marrow cells. Bone marrow cells from 5FU treated
mice were transduced with a control vector or miR-150. GFP+ cells
were sorted two days after transduction and assayed for erythroid
colony forming units (CFU-E). Using the bone marrow cells from the
transplant recipients, it was found that miR-150 overexpression
resulted in a statistically significant increase in megakaryocyte
colony-forming units (CFU-Mk) (FIG. 3A), coupled with a dramatic
decrease in erythroid colony formation (FIG. 13). Representative
erythroid colonies from control vector- or miR-150-transduced bone
marrow cells. Note that rare erythroid colonies formed from miR-150
transduced cells showed reduced cell number. These gain of function
experiments indicate that miR-150 regulates MEP fate, and not
simply post-commitment megakaryocyte expansion.
Example 4
Effects of Loss of Function of miR-150 in In Vitro Differentiation
of Progenitor Cells
[0247] To complement these miR-150 forced expression studies, a
loss-of-function approach was used. MEP cells were isolated from
bone marrow, and assayed for megakaryocyte colony formation in the
presence or absence of an antagomir (a cholesterol-modified
antisense oligonucleotide (13) directed against miR-150. Murine
bone marrow cells were cultured in the presence of solvent (PBS),
antagomir against miR-150 (anti-150) or a scrambled antagomir.
miR-150 expression was measured with quantitative RT-PCR after 3
days of treatment (FIG. 14). Data represent 2.DELTA.Ct. Error bars
represent standard deviation of measurement. MEPs treated with
antagomir-150 showed more than a 4-fold decrease in CFU-Mk,
compared to controls (see FIG. 3B). A similar effect was observed
using purified uncommitted Lin-Kit+Sca+hematopoietic stem cells
(FIG. 3C). Interestingly, miR-150 knock-down megakaryocyte colonies
showed normal morphology and acetylcholinesterase activity (FIG.
15), indicating that miR-150 might be dispensable once MEP
commitment to the megakaryocyte lineage is established. To confirm
a role of miR-150 in the physiological regulation of MEP fate, we
treated mice with the anemia-inducing drug phenylhydrazine, and
then measured miR-150 expression in lineage-negative bone marrow
cells. miR-150 expression was significantly decreased in this
setting of increased demand for erythropoiesis, consistent with
miR-150's role in promoting megakaryopoiesis at the expense of
erythropoiesis (FIG. 3D).
Example 5
miR-150 Regulates the c-myc Gene
[0248] The experiments described above firmly establish an
important role of miR-150 in the specification of megakaryocytes
from MEPs. To determine the mRNA targets of miR-150 that explain
its effect on megakaryocytic/erythroid outcome, the targets
predicted in common among several sequence-based prediction
algorithms (14-16) were analyzed. MYB (also known as c-myb) was
tested as a candidate because several recently reported mouse
models, in which MYB activity was reduced due to either mutation or
the serendipitous integration of a transgene near the MYB locus,
displayed thrombocytosis and anemia (17-21). The expression of MYB
messenger RNA, however, is not immediately indicative of a role in
MEP differentiation, as similar expression in MEPs and early
erythroid and megakaryocyte populations were noted (FIG. 16).
Examination of the human MYB 3'UTR, however, identified multiple
conserved miR-150 putative sites (FIG. 17). To establish miR-150 as
a functional negative regulator of MYB, the erythroblastic cell
line K562 was experimented in, which has the potential to be
induced to differentiate into erythroid or megakaryocytic cells. A
dramatic reduction in MYB protein level upon ectopic expression of
miR-150 (FIG. 4A) was observed. Next, the MYB 3' UTR was cloned
into a luciferase reporter, and it was found that miR-150 repressed
reporter activity by more than 6-fold, again consistent with
miR-150 targeting MYB. Importantly, mutation of the 4 candidate
miR-150 binding sites abrogated miR-150 repression, and a mutant
miR-150 construct designed to be complementary to the mutant MYB
3'UTR binding sites restored miR-150 mediated repression, but did
not affect the wild-type MYB 3'UTR (FIG. 4B, 4C). These experiments
establish that miR-150 negatively regulates the protein level of
MYB directly through its 3' UTR.
[0249] Lastly, the question of whether miR-150 repression of MYB
explains miR-150's erythroid/megakaryocytic effects was addressed.
Using the in vitro CD34+ human bone marrow cell culture, consistent
with reports that mice with reduced MYB activity display
megakaryocytosis (17-21), two independent shRNA constructs that
knocked down MYB expression (FIG. 18A) promoted megakaryocyte
development (FIG. 18B). In contrast, forced expression of a MYB
cDNA construct lacking its 3'UTR resulted in a decrease in
megakaryocytes (FIG. 4D, 4E). Moreover, the MYB expression
construct rescued the megakaryocytopoiesis-promoting effect of
miR-150 to a large extent, indicating that MYB is a functionally
relevant downstream effector of miR-150 (FIG. 4D, 4E). This MYB
effect is consistent with a recent study showing MEPs with reduced
MYB activity favor decision towards megakaryocytic as opposed to
erythroid differentiation (20). In contrast to total loss of MYB
function, which results in complete hematopoietic failure (19), our
data indicate that modest modulation of MYB expression levels by
miRNA can have important effects on lineage specification. These
results are particularly interesting in light of the recent report
of miR-150 regulation of MYB activity in B-lineage lymphocytes
(22). It has been generally assumed that miRNAs have a plethora of
targets that vary depending on cellular context. Remarkably, MYB
appears to be a critical target of miR-150 both in establishing MEP
fate and in regulating the differentiation of lineage-committed
B-cells. This observation indicates that a single mRNA target of
miRNAs might explain much of the miRNAs function, even in
completely different developmental contexts. Our studies, of
course, do not exclude the possibility that additional factors may
also contribute to the establishment of MEP fate.
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TABLE-US-00005 [0271] TABLE 1 Quantitative RT-PCR assays used in
this study Gene of interest Assay Human Myb Hs00193527_m1
Eukaryotic 18S 4333760T miR-150 4373127 Mouse PF4 Mm00451315_g1
TABLE-US-00006 TABLE 2 Antibodies for cell surface markers Antigen
Fluorophore Clone Source Mouse CD71 PE C2 BD Pharmingen Mouse
Ter119 APC TER-1 19 BD Pharmingen Mouse CD41 PE MWReg30 BD
Pharmingen Mouse CD3.epsilon. biotin 145-2C1 1 BD Pharmingen Mouse
CD4 biotin L3T4 BD Pharmingen Mouse CD8a biotin 53-6.7 BD
Pharmingen Mouse biotin RA3-6B2 BD Pharmingen CD45R/B220 Mouse
Ter119 biotin TER-1 19 BD Pharmingen Mouse CD1 1b biotin M1/70 BD
Pharmingen Mouse Gr1 biotin RB6-8C5 BD Pharmingen Mouse c-Kit APC
2B8 BD Pharmingen Mouse Sca-1 PE Cat# Caltag MSCA04-3 Mouse CD34
Pacific blue RAM34 eBioscience Mouse CD16/32 PE-Cy7 93 eBioscience
Streptavidine PerCP Cat# BD Pharmingen 554064 Human CD71 FITC and
PE-Cy5 C2 BD Pharmingen Human CD34 APC 581 BD Pharmingen Humn CD61
FITC 2C9.G2 BD Pharmingen Human CD41 PE and FITC HIP8 BD Pharmingen
Human CD45 APC-Cy7 2D1 BD Pharmingen Human CD45RA FITC L48 BD
Pharmingen Human GlyA PE CLR-ery-1 CALTAG/ (AME-1) Invitrogen
TABLE-US-00007 TABLE 3 Comparative marker selection result for ERY
samples vs. MEGA samples Feature Description TTEST_Score Feature P
FDR(BH) Q Value FWER EAM217 hmr-miR- -6.134193365 6.00E-04 0.00373
0.00197 0.00148 150_rfam7.0 EAM161 hmr-miR- -4.939403406 7.60E-04
0.00441 0.00225 0.02214 28_rfam7.0 EAM163 hmr-miR-142- -3.738371725
0.0012 0.00653 0.00333 0.26634 3p_rfam7.0 EAM371 hmr-miR-
-3.42554054 6.00E-04 0.00373 0.00197 0.45006 342_rfam7.0 EAM278
hmr-miR-98 rfam7.0 -2.98741 7405 0.00524 0.02682 0.01368 0.76548
EAM263 hmr-miR- -2.93748816 0 0 0 0.79334 26a_rfam7.0 EAM224
hmr-miR-17- 2.052993319 0.00604 0.02919 0.01489 0.99828 5p_rfam7.0
Normalized miRNA expression data for ERY populations (ERY1, ERY2,
ERY3) and MEGA populations (MEGA1, MEGA2) were log2 transformed,
thresholded at 6, and filtered to retain miRNAs with maxiumum
expression over 8. Markers were selected using the
ComparativeMarkerSelection module in GenePattern, with median-based
t-test and 50,000 permutations. The table below shows features with
BH-FDR of less than 0.05. Negative TTEST_Score means higher
expression in MEGA samples, whereas positive number reflects higher
expression in ERY samples. The table was sorted according to
TTEST_Score. Feature: miRNA detection probe ID; Description:
Detection probe annotation based on miRBASE 7.0; TTEST_Score:
Median-based t-test score; Feature P: Nominal P value, after 50,000
permutations; FDR(BH): Benjamini-Hochberg false discovery rate; Q
Value: q-value; FWER: Family-wise error rate.
TABLE-US-00008 TABLE 4 List of capture probes for initial miRNA
capture /5AmMC6/indicates ' amino modification. Probes were
synthesized by IDT. /5AmMC6/ACTCAGAAGGACAAGTAGAGTTTT (SEQ. ID. No.
26) /5AmMC6/GTGGTAATCCCTGGCAATGTGAT (SEQ. ID. No. 27)
/5AmMC6/ACACTCTAAAGGGAACCATTTT (SEQ. ID. No. 28)
/5AmMC6/GGAAATCCCTGGCAATGTGAT (SEQ. ID. No. 29)
/5AmMC6/AAAGAAGTGCACCATGTTTGTTT (SEQ. ID. No. 30)
/5AmMC6/AAAGTGTCAGATACGGTGTGG (SEQ. ID. No. 31)
/5AmMC6/AAGAAGTGCACCGCGAATGT (SEQ. ID. No. 32)
/5AmMC6/ACAGTTCTTCAACTGGCAGCTT (SEQ. ID. No. 33)
/5AmMC6/AACACTCTGAAGGGAAGCGC (SEQ. ID. No. 34)
/5AmMC6/CTACCTGCACTATAAGCACTTTA (SEQ. ID. No. 35)
/5AmMC6/CACTCTAAAAGGATGCACTTT (SEQ. ID. No. 36)
/5AmMC6/TCAGTTTTGCATGGATTTGCACA (SEQ. ID. No. 37)
/5AmMC6/TTCACCAAAGGGAAGCACTTT (SEQ. ID. No. 38)
/5AmMC6/CCCAACAACATGAAACTACCTA (SEQ. ID. No. 39)
/5AmMC6/ACACTCTAAAGGGAAGTGCGTT (SEQ. ID. No. 40)
/5AmMC6/ACAAAGTTCTGTAGTGCACTGA (SEQ. ID. No. 41)
/5AmMC6/CTCCCTTCTTTCCTCCCGTC (SEQ. ID. No. 42)
/5AmMC6/CTAGTACATCATCTATACTGTA (SEQ. ID. No. 43)
/5AmMC6/CTCACACCTAGGTTCCAAGGATT (SEQ. ID. No. 44)
/5AmMC6/tgAGCTACAGTGCTTCATCTCA (SEQ. ID. No. 45)
/5AmMC6/TTACAGATGGATACCGTGCAATT (SEQ. ID. No. 46)
/5AmMC6/CCATCTTTACCAGACAGTGTT (SEQ. ID. No. 47)
/5AmMC6/CCACGACCGACGCCACGCC (SEQ. ID. No. 48)
/5AmMC6/CTACCATAGGGTAAAACCACT (SEQ. ID. No. 49)
/5AmMC6/CCTCTAAAAGGAAGCACTTTCT (SEQ. ID. No. 50)
/5AmMC6/TGGAGACACGTGCACTGTAGA (SEQ. ID. No. 51)
/5AmMC6/GAACATACAAAGGGTATCCTCT (SEQ. ID. No. 52)
/5AmMC6/TTCACATAGGAATAAAAAGCCATA (SEQ. ID. No. 53)
/5AmMC6/CGAATATAACACGGTCGATCT (SEQ. ID. No. 54)
/5AmMC6/ACAGCTGGTTGAAGGGGACCAA (SEQ. ID. No. 55)
/5AmMC6/CCTCCAGCCCCTCCAGGGCT (SEQ. ID. No. 56)
/5AmMC6/GGGGTATTTGACAAACTGACA (SEQ. ID. No. 57)
/5AmMC6/TCAATCACAGATAGCACCCCT (SEQ. ID. No. 58)
/5AmMC6/GCAAAAATGTGCTAGTGCCAAA (SEQ. ID. No. 59)
/5AmMC6/GTAGTGCAACTATGCAAAACT (SEQ. ID. No. 60)
/5AmMC6/TCATACAGCTAGATAACCAAAGA (SEQ. ID. No. 61)
/5AmMC6/TGGTGGCAGTGGTGGGAT (SEQ. ID. No. 62)
/5AmMC6/CTTCCAGTCGGGGATGTTTACA (SEQ. ID. No. 63)
/5AmMC6/ACACTCTAAAGGGATGCACGAT (SEQ. ID. No. 64)
/5AmMC6/ACACAAATTCGGTTCTACAGGG (SEQ. ID. No. 65)
/5AmMC6/AAAGTGCTTCTTACCTCCAGAT (SEQ. ID. No. 66)
/5AmMC6/ACCCTCCACCATGCAAGGGATG (SEQ. ID. No. 67)
/5AmMC6/ACCTCTAAAGGGGAGCGCTT (SEQ. ID. No. 68)
/5AmMC6/CCTATCTCCCCTCTGGACC (SEQ. ID. No. 69)
/5AmMC6/ACACTCTAAAGGGAGGCACTTT (SEQ. ID. No. 70)
/5AmMC6/GGCTGTCAATTCATAGGTCAG (SEQ. ID. No. 71)
/5AmMC6/TCCAGGAGCTCACAATCTAGTG (SEQ. ID. No. 72)
/5AmMC6/CGGCTGCAACACAAGACACGA (SEQ. ID. No. 73)
/5AmMC6/GTTACCGCAGGCTGCTCTGG (SEQ. ID. No. 74)
/5AmMC6/CAGTGAATTCTACCAGTGCCATA (SEQ. ID. No. 75)
/5AmMC6/AGAAAGCGCTTCCCTGTAGAG (SEQ. ID. No. 76)
/5AmMC6/TGTGAGTTCTACCATTGCCAAA (SEQ. ID. No. 77)
/5AmMC6/AGCCAAGTAATGGAGAACAGG (SEQ. ID. No. 78)
/5AmMC6/CGAAGGCAACACGGATAACCTA (SEQ. ID. No. 79)
/5AmMC6/AGAAAGCGCTTCCCTCTAGAG (SEQ. ID. No. 80)
/5AmMC6/TCACTTTTGTGACTATGCAA (SEQ. ID. No. 81)
/5AmMC6/ACAGAAAGGGCTTCCCTTTGC (SEQ. ID. No. 82)
/5AmMC6/CCAAGTTCTGTCATGCACTGA (SEQ. ID. No. 83)
/5AmMC6/TCGGTCCCTCGGGCCAGGG (SEQ. ID. No. 84)
/5AmMC6/GGAGTGAAGACACGGAGCCAGA (SEQ. ID. No. 85)
/5AmMC6/TCTAAGCCAGCATGTGAAACCA (SEQ. ID. No. 86)
/5AmMC6/ACAAAGTTCTGTGATGCACTGA (SEQ. ID. No. 87)
/5AmMC6/GCAAGGCAGTGGCCTGTACA (SEQ. ID. No. 88)
/5AmMC6/GCTGAGAGTGTAGGATGTTTACA (SEQ. ID. No. 89)
/5AmMC6/TCCAGCAAAGGGAAGCGCTT (SEQ. ID. No. 90)
/5AmMC6/AACCGATTTCAGATGGTGCTAG (SEQ. ID. No. 91)
/5AmMC6/ACCCTCTATAGGGAAGCGCGT (SEQ. ID. No. 92)
/5AmMC6/GTCATCATTACCAGGCAGTATTA (SEQ. ID. No. 93)
/5AmMC6/CAGGTAACAACTCGCCGCTC (SEQ. ID. No. 94)
/5AmMC6/AACCAATGTGCAGACTACTGTA (SEQ. ID. No. 95)
/5AmMC6/ACTGCACTTTTATGAATAAGCTC (SEQ. ID. No. 96)
/5AmMC6/GCTGGGTGGAGAAGGTGGTGAA (SEQ. ID. No. 97)
/5AmMC6/AACGCTCCAAAAGAAGGCACT (SEQ. ID. No. 98)
/5AmMC6/GCCAATATTTCTGTGCTGCTA (SEQ. ID. No. 99)
/5AmMC6/ACCAGAACTGAGTCCACAGGG (SEQ. ID. No. 100)
/5AmMC6/CGCAAGGTCGGTTCTACGGGTG (SEQ. ID. No. 101)
/5AmMC6/TCCCGTCGCCAGCGGAGGC (SEQ. ID. No. 102)
/5AmMC6/ACACCGAGGAGCCCATCATGAT (SEQ. ID. No. 103)
/5AmMC6/ACTGAAACCAAGTATGGGTCGC (SEQ. ID. No. 104)
/5AmMC6/CCTGCATGACGGCCTGCAAGACA (SEQ. ID. No. 105)
/5AmMC6/CAGCCCTCCTGGTGGCTGG (SEQ. ID. No. 106)
/5AmMC6/ATAAGGATTTTTAGGGGGCATTA (SEQ. ID. No. 107)
/5AmMC6/ATCTACACTGGCTACTGAGCC (SEQ. ID. No. 108)
/5AmMC6/TATTAGGAACACATCGCAAAAA (SEQ. ID. No. 109)
/5AmMC6/CGCGACTGCGTCACCGGCC (SEQ. ID. No. 110)
/5AmMC6/ACCAGCTAACAATACACTGCCA (SEQ. ID. No. 111)
/5AmMC6/CCTGCGCCATCTCCTCTAC (SEQ. ID. No. 112)
/5AmMC6/ATGGGACATCCTACATATGCAA (SEQ. ID. No. 113)
/5AmMC6/ACTGTGTTTCAGCTCAGTAGGCA (SEQ. ID. No. 114)
/5AmMC6/TTCAAAACATGAATTGCTGCTG (SEQ. ID. No. 115)
/5AmMC6/CGAACACAGCAGGGATAACCAC (SEQ. ID. No. 116)
/5AmMC6/GTACCCCTGGAGATTCTGATAA (SEQ. ID. No. 117)
/5AmMC6/ACTGCAGAACTGTTCCCGCTG (SEQ. ID. No. 118)
/5AmMC6/TCACGCGAGCCGAACGAACAAA (SEQ. ID. No. 119)
/5AmMC6/AGAAAATGCCCCTCAGTTTTGA (SEQ. ID. No. 120)
/5AmMC6/ACAAAAGTTGCCTTTGTGTGAT (SEQ. ID. No. 121)
/5AmMC6/AGACGGGAGGAGAGGAGTGA (SEQ. ID. No. 122)
/5AmMC6/ACACAGGACCTGGAGTCAGGAG (SEQ. ID. No. 123)
/5AmMC6/ATCGGGAGGGGACTGAGCCT (SEQ. ID. No. 124)
/5AmMC6/CCTACGTTCCATAGTCTACCA (SEQ. ID. No. 125)
/5AmMC6/CTCGGGGCAGCTCAGTACAG (SEQ. ID. No. 126)
/5AmMC6/GCGCATGTTCTATGGTCAACCA (SEQ. ID. No. 127)
/5AmMC6/CGAGCCGGTCGAGGTCCGGT (SEQ. ID. No. 128)
/5AmMC6/ACAGAGAGCTTGCCCTTGTATA (SEQ. ID. No. 129)
/5AmMC6/TCTCGTGACATGATGATCCCCG (SEQ. ID. No. 130)
/5AmMC6/TATGAACAATTTCTAGGAAT (SEQ. ID. No. 131)
/5AmMC6/AGAAAGCGCTTTCCTTTGTAGA (SEQ. ID. No. 132)
/5AmMC6/GGCGGACACGACATTCCCGAT (SEQ. ID. No. 133)
/5AmMC6/CACATGGCCAAAACAGAGAAGA (SEQ. ID. No. 134)
/5AmMC6/GTCTCAGTTTCCTCTGCAAACA (SEQ. ID. No. 135)
/5AmMC6/CCACCCAATGACCTACTCCAAG (SEQ. ID. No. 136)
/5AmMC6/GCTGTAAACATCCGACTGAAAG (SEQ. ID. No. 137)
/5AmMC6/TCATCTCGCCCGCAAAGACC (SEQ. ID. No. 138)
/5AmMC6/ATGCTTTTTGGGGTAAGGGCTT (SEQ. ID. No. 139)
/5AmMC6/AGAAAGTGCTTTCTTTTGGAGAA (SEQ. ID. No. 140)
/5AmMC6/ACGGCATTACCAGACAGTATTA (SEQ. ID. No. 141)
/5AmMC6/GAAAGTGCTTCTTTCCTCGAGAA (SEQ. ID. No. 142)
/5AmMC6/TCTCTGCAGGCCCTGTGCTTTGC (SEQ. ID. No. 143)
/5AmMC6/CACAGGTTAAAGGGTCTCAGGGA (SEQ. ID. No. 144)
/5AmMC6/TGTTGCAGCGCTTCATGTTT (SEQ. ID. No. 145)
/5AmMC6/ACAAATTCGGTTCTACAGGGTA (SEQ. ID. No. 146)
/5AmMC6/AGCCACAGTCACCTTCTGATCT (SEQ. ID. No. 147)
/5AmMC6/TGATAGCCCTGTACAATGCTGCT (SEQ. ID. No. 148)
/5AmMC6/CATGCATACATGCACACATACAT (SEQ. ID. No. 149)
/5AmMC6/TCATAGCCCTGTACAATGCTGCT (SEQ. ID. No. 150)
/5AmMC6/CAACAAACATTTAATGAGGCC (SEQ. ID. No. 151)
/5AmMC6/AACTATACAATCTACTACCTCA (SEQ. ID. No. 152)
/5AmMC6/TGATGGACAACAAATTAGGTA (SEQ. ID. No. 153)
/5AmMC6/ACTATGCAACCTACTACCTCT (SEQ. ID. No. 154)
/5AmMC6/TATCTCACAGAATAAACTTGGTA (SEQ. ID. No. 155)
/5AmMC6/TTCAGCTATCACAGTACTGTA (SEQ. ID. No. 156)
/5AmMC6/TCACATCAGTGCCATTCTAAATA (SEQ. ID. No. 157)
/5AmMC6/CTATACAACCTCCTACCTCA (SEQ. ID. No. 158)
/5AmMC6/GTCTTATGTGTGCGTGTATGTAT (SEQ. ID. No. 159)
/5AmMC6/CTCAATAGACTGTGAGCTCCTT (SEQ. ID. No. 160)
/5AmMC6/GTGTAGGTGTGTGTATGTATAT (SEQ. ID. No. 161)
/5AmMC6/AACCTATCCTGAATTACTTGAA (SEQ. ID. No. 162)
/5AmMC6/CAGACACACGCACATCAGTCATA (SEQ. ID. No. 163)
/5AmMC6/TCCATCATCAAAACAAATGGAGT (SEQ. ID. No. 164)
/5AmMC6/GGACACCAAGATCAATGAAAGAGGCA (SEQ. ID. No. 165)
/5AmMC6/AGGCAAAGGATGACAAAGGGAA (SEQ. ID. No. 166)
/5AmMC6/TCACCAGTGCCAGTCGAAGAA (SEQ. ID. No. 167)
/5AmMC6/GAACAGGTAGTCTAAACACTGGG (SEQ. ID. No. 168)
/5AmMC6/TGTGAAAAGCACTATACTACGTA (SEQ. ID. No. 169)
/5AmMC6/ATCCAGTCAGTTCCTGATGCAGTA (SEQ. ID. No. 170)
/5AmMC6/AGACTAGATATGGAAGGGTGA (SEQ. ID. No. 171)
/5AmMC6/GCTGCAAACATCCGACTGAAAG (SEQ. ID. No. 172)
/5AmMC6/TCTGGGCACACGGAGGGAGA (SEQ. ID. No. 173)
/5AmMC6/TAACCGATTTCAAATGGTGCTA (SEQ. ID. No. 174)
/5AmMC6/ACGGTGAGGCTTTGGCTAGAT (SEQ. ID. No. 175)
/5AmMC6/AACAATACAACTTACTACCTCA (SEQ. ID. No. 176)
/5AmMC6/AGAGGCAGGCACTCAGGCAGA (SEQ. ID. No. 177)
/5AmMC6/ATACATACTTCTTTACATTCCA (SEQ. ID. No. 178)
/5AmMC6/TGGGCGACCCAGAGGGACA (SEQ. ID. No. 179)
/5AmMC6/GCTGAGTGTAGGATGTTTACA (SEQ. ID. No. 180)
/5AmMC6/AGAGGTTAAGACAGCAGGGCTG (SEQ. ID. No. 181)
/5AmMC6/ATGCCCTTTTAACATTGCACTG (SEQ. ID. No. 182)
/5AmMC6/GGTTCAAACCATGAGTCGAGCT (SEQ. ID. No. 183)
/5AmMC6/CTACGCGTATTCTTAAGCAATAA (SEQ. ID. No. 184)
/5AmMC6/GGAGTCGAGTGATGGTTCAAA (SEQ. ID. No. 185)
/5AmMC6/AGAACAATGCCTTACTGAGTA (SEQ. ID. No. 186)
/5AmMC6/GAATAATGACAGGCTCACCGTA (SEQ. ID. No. 187)
/5AmMC6/TCTTCCCATGCGCTATACCTCT (SEQ. ID. No. 188)
/5AmMC6/TACTATGCAACCTACTACTCT (SEQ. ID. No. 189)
/5AmMC6/CCACACACTTCCTTACATTCCA (SEQ. ID. No. 190)
/5AmMC6/CTGAGGGGCCTCAGACCGAGCT (SEQ. ID. No. 191)
/5AmMC6/GAGGGAGGAGAGCCAGGAGAAGC (SEQ. ID. No. 192)
/5AmMC6/TAACTGCACTAGATGCACCTTA (SEQ. ID. No. 193)
/5AmMC6/ACAAGCTTTTTGCTCGTCTTAT (SEQ. ID. No. 194)
/5AmMC6/CTACCTGCACTATGAGCACTTTG (SEQ. ID. No. 195)
/5AmMC6/GGCCGTGACTGGAGACTGTTA (SEQ. ID. No. 196)
/5AmMC6/GGGGACGAAATCCAAGCGCAGC (SEQ. ID. No. 197)
/5AmMC6/CACAGTTGCCAGCTGAGATTA (SEQ. ID. No. 198)
/5AmMC6/AATAGGTCAACCGTGTATGATT (SEQ. ID. No. 199)
/5AmMC6/ACATGGTTAGATCAAGCACAA (SEQ. ID. No. 200)
/5AmMC6/GCAGAAGCATTTCCACACAC (SEQ. ID. No. 201)
/5AmMC6/ACAACCAGCTAAGACACTGCCA (SEQ. ID. No. 202)
/5AmMC6/CCCCTATCACGATTAGCATTAA (SEQ. ID. No. 203)
/5AmMC6/AGGCGAAGGATGACAAAGGGAA (SEQ. ID. No. 204)
/5AmMC6/ACAAGTGCCTTCACTGCAGT (SEQ. ID. No. 205)
/5AmMC6/GTCTGTCAATTCATAGGTCAT (SEQ. ID. No. 206)
/5AmMC6/TCCAGCACTGTCCGGTAAGATG (SEQ. ID. No. 207)
/5AmMC6/ATCCAATCAGTTCCTGATGCAGTA (SEQ. ID. No. 208)
/5AmMC6/AAAGCAAGTACATCCACGTTTA (SEQ. ID. No. 209)
/5AmMC6/ACTACCTGCACTGTAAGCACTTTG (SEQ. ID. No. 210)
/5AmMC6/AAGCGGTTTACCATCCCACATA (SEQ. ID. No. 211)
/5AmMC6/TATCTGCACTAGATGCACCTTA (SEQ. ID. No. 212)
/5AmMC6/TAGTTGGCAAGTCTAGAACCA (SEQ. ID. No. 213)
/5AmMC6/AACCCACCGACAGCAATGAATGTT (SEQ. ID. No. 214)
/5AmMC6/CTACTAAAACATGGAAGCACTTA (SEQ. ID. No. 215)
/5AmMC6/GAACAGGTAGTCTGAACACTGGG (SEQ. ID. No. 216)
/5AmMC6/AGAAAGCACTTCCATGTTAAAGT (SEQ. ID. No. 217)
/5AmMC6/GAACAGATAGTCTAAACACTGGG (SEQ. ID. No. 218)
/5AmMC6/CCACTGAAACATGGAAGCACTTA (SEQ. ID. No. 219)
/5AmMC6/TCAGTTTTGCATAGATTTGCACA (SEQ. ID. No. 220)
/5AmMC6/CAGCAGGTACCCCCATGTTA (SEQ. ID. No. 221)
/5AmMC6/CTAGTGGTCCTAAACATTTCAC (SEQ. ID. No. 222)
/5AmMC6/ACACTCAAACATGGAAGCACTTA (SEQ. ID. No. 223)
/5AmMC6/AGGCATAGGATGACAAAGGGAA (SEQ. ID. No. 224)
/5AmMC6/ACTTACTGGACACCTACTAGG (SEQ. ID. No. 225)
/5AmMC6/CAGCCGCTGTCACACGCACAG (SEQ. ID. No. 226)
/5AmMC6/AAAGGCATCATATAGGAGCTGGA (SEQ. ID. No. 227)
/5AmMC6/CTGCCTGTCTGTGCCTGCTGT (SEQ. ID. No. 228)
/5AmMC6/GCCCTGGACTAGGAGTCAGCA (SEQ. ID. No. 229)
/5AmMC6/CACAAGTTCGGATCTACGGGTT (SEQ. ID. No. 230)
/5AmMC6/AGAGGCAGGCATGCGGGCAG (SEQ. ID. No. 231)
/5AmMC6/GCTACCTGCACTGTAAGCACTTTT (SEQ. ID. No. 232)
/5AmMC6/TCACCATTGCTAAAGTGCAATT (SEQ. ID. No. 233)
/5AmMC6/CACAAATTCGGATCTACAGGGTA (SEQ. ID. No. 234)
/5AmMC6/AAACGTGGAATTTCCTCTATGT (SEQ. ID. No. 235)
/5AmMG6/ACAAACACCATTGTCACACTCCA (SEQ. ID. No. 236)
/5AmMC6/AAAGATCAACCATGTATTATT (SEQ. ID. No. 237)
/5AmMC6/CGCGTACCAAAAGTAATAATG (SEQ. ID. No. 238)
/5AmMC6/AGCCACAATCACCTTCTGATCT (SEQ. ID. No. 239)
/5AmMC6/GCCCTTTCATCATTGCACTG (SEQ. ID. No. 240)
/5AmMC6/TCTCTGCAGGCCGTGTGCTTTGC (SEQ. ID. No. 241)
/5AmMC6/TCCCTCTGGTCAACCAGTCACA (SEQ. ID. No. 242)
/5AmMC6/ACGGTTTTACCAGACAGTATTA (SEQ. ID. No. 243)
/5AmMC6/GTAGTGCTTTCTACTTTATG (SEQ. ID. No. 244)
/5AmMC6/ACGTGGATTTTCCTCTATGAT (SEQ. ID. No. 245)
/5AmMC6/CCCCTATCACAATTAGCATTAA (SEQ. ID. No. 246)
/5AmMC6/GGCCTTCTGACTCCAAGTCCAG (SEQ. ID. No. 247)
/5AmMC6/TGTAAACCATGATGTGCTGCTA (SEQ. ID. No. 248)
/5AmMC6/AAGATGTGGACCATATTACATA (SEQ. ID. No. 249)
/5AmMC6/ACTCACCGACAGGTTGAATGTT (SEQ. ID. No. 250)
/5AmMC6/GGCCTTCTGACCCTAAGTCCAG SEQ. ID. No. 251)
/5AmMC6/CACAAACCATTATGTGCTGCTA (SEQ. ID. No. 252)
/5AmMC6/AAAGAGGTTAACCAGGTGTGTT (SEQ. ID. No. 253)
/5AmMC6/TAACTGTACAAACTACTACCTCA (SEQ. ID. No. 254)
/5AmMC6/CGAACTCACCACGGACAACCTC (SEQ. ID. No. 255)
/5AmMC6/ACAGGCCGGGACAAGTGCAATAT (SEQ. ID. No. 256)
/5AmMC6/CTTCTTTGCAGATGAGACTGA (SEQ. ID. No. 257)
/5AmMC6/TAACCCATGGAATTCAGTTCTCA (SEQ. ID. No. 258)
/5AmMC6/TGCAAAGTTGCTCGGGTAACCT (SEQ. ID. No. 259)
/5AmMC6/AACCATACAACCTACTACCTCA (SEQ. ID. No. 260)
/5AmMC6/AACATGGATTTTCCTCTATGAT (SEQ. ID. No. 261)
/5AmMC6/AACAACAAAATCACTAGTCTTCCA (SEQ. ID. No. 262)
/5AmMC6/GAATTCATCACGGCCAGCCTCT (SEQ. ID. No. 263)
/5AmMC6/ACTTTCGGTTATCTAGCTTTAT (SEQ. ID. No. 264)
/5AmMC6/AGAGGAGAGCCGTGTATGAC (SEQ. ID. No. 265)
/5AmMC6/ACAGCACAAACTACTAGCTCA (SEQ. ID. No. 266)
/5AmMC6/TTGAGAGTGCCATTATCTGGG (SEQ. ID. No. 267)
/5AmMC6/AACTATACAACCTACTACCTCA (SEQ. ID. No. 268)
/5AmMC6/GCTGCCGTATATGTGATGTCACT (SEQ. ID. No. 269)
/5AmMC6/AACCACACAACCTACTACCTCA (SEQ. ID. No. 270)
/5AmMC6/CAGCATGGAGTCCTCCAGGTTG (SEQ. ID. No. 271)
/5AmMC6/CCGACCATGGCTGTAGACTGTTA (SEQ. ID. No. 272)
/5AmMC6/TCCTCATGGAAGGGTTCCCCACT (SEQ. ID. No. 273)
/5AmMC6/ACACCAATGCCCTAGGGGATGCG (SEQ. ID. No. 274)
/5AmMC6/TGACTGCAGAGCAAAAGACAC (SEQ. ID. No. 275)
/5AmMC6/TGGCATTCACCGCGTGCCTTA (SEQ. ID. No. 276)
/5AmMC6/AGCCTATGGAATTCAGTTCTCA (SEQ. ID. No. 277)
/5AmMC6/TCACAAGTTAGGGTCTCAGGGA (SEQ. ID. No. 278)
/5AmMC6/AAAGAAGTATATGCATAGGAAA (SEQ. ID. No. 279)
/5AmMC6/CACAAGATCGGATCTACGGGT (SEQ. ID. No. 280)
/5AmMC6/TTTTCCCATGCCCTATACCTCT (SEQ. ID. No. 281)
/5AmMC6/CGCCAATATTTACGTGCTGCTA (SEQ. ID. No. 282)
/5AmMC6/AAGAATCTTGTCCCGCAGGTCCT (SEQ. ID. No. 283)
/5AmMC6/AACACTGATTTCAAATGGTGCTA (SEQ. ID. No. 284)
/5AmMC6/AATGAAAGCCTACCATGTACAA (SEQ. ID. No. 285)
/5AmMC6/CTTCAGTTATCACAGTACTGTA (SEQ. ID. No. 286)
/5AmMC6/AGACATGGAGGAGCCATCCAG (SEQ. ID. No. 287)
/5AmMC6/ACAGGAGTCTGAGCATTTGA (SEQ. ID. No. 288)
/5AmMC6/AAGAGGTTTCCCGTGTATGTTTCA (SEQ. ID. No. 289)
/5AmMC6/ATCTGCACTGTCAGCACTTTA (SEQ. ID. No. 290)
/5AmMC6/GGAGATTGGCCATGTAATACT (SEQ. ID. No. 291)
/5AmMC6/GCATTATTACTCACGGTACGA (SEQ. ID. No. 292)
/5AmMC6/ACAAACCACAGTGTGCTGCTG (SEQ. ID. No. 293)
/5AmMC6/AGCCAAGCTCAGACGGATCCGA (SEQ. ID. No. 294)
/5AmMC6/AACCCACCGACAACAATGAATGTT (SEQ. ID. No. 295)
/5AmMC6/ACTGATATCAGCTCAGTAGGCAC (SEQ. ID. No. 296)
/5AmMC6/GAAAGTGCCCTCAAGGCTGAGTG (SEQ. ID. No. 297)
/5AmMC6/TCCATCATTACCCGGCAGTATTA (SEQ. ID. No. 298)
/5AmMC6/GACCTCAGCTATGACAGCACTT (SEQ. ID. No. 299)
/5AmMC6/TAAACGGAACCACTAGTGACTTG (SEQ. ID. No. 300)
/5AmMC6/GAAAAACGCCCCCTGGCTTGAAA (SEQ. ID. No. 301)
/5AmMC6/TCAGAGCGAGACAAGTGCAATG (SEQ. ID. No. 302)
/5AmMC6/CCCTCAAAAAGGAAGCACTTT (SEQ. ID. No. 303)
/5AmMC6/GGCGGAACTTAGCCACTGTGAA (SEQ. ID. No. 304)
/5AmMC6/GAAAGTGCTCCCTTTTGGAGAA (SEQ. ID. No. 305)
/5AmMC6/ACAGGATTGAGGGGGGGCCCT (SEQ. ID. No. 306)
/5AmMC6/ACACTCTAAAAGGAGGCACTTT (SEQ. ID. No. 307)
/5AmMC6/ATGTATGTGGGACGGTAAACCA (SEQ. ID. No. 308)
/5AmMC6/ATCCTCTAAAAAGATGCACTTT (SEQ. ID. No. 309)
/5AmMC6/GCTTTGACAATACTATTGCACTG (SEQ. ID. No. 310)
/5AmMC6/AGAAAGTACTTCCCTCTGGAG (SEQ. ID. No. 311)
/5AmMC6/TCACCAAAACATGGAAGCACTTA (SEQ. ID. No. 312)
/5AmMC6/ACAGTCCAAAGGGAAGCACTTT (SEQ. ID. No. 313)
/5AmMC6/GCTTCCAGTCGAGGATGTTTACA (SEQ. ID. No. 314)
/5AmMC6/AACAGAAAGTGCTTCCCTCAAGAG (SEQ. ID. No. 315)
/5AmMC6/TCCAGTCAAGGATGTTTACA (SEQ. ID. No. 316)
/5AmMC6/GCCTCTAAAAGGAAGCACTTT (SEQ. ID. No. 317)
/5AmMC6/CAGCTATGCCAGCATCTTGCCT (SEQ. ID. No. 318)
/5AmMC6/AAACCTCTAAAAGGATGCACTTT (SEQ. ID. No. 319)
/5AmMC6/GCAACTTAGTAATGTGCAATA (SEQ. ID. No. 320)
/5AmMC6/AGAAAGTGCATCCCTCTGGAG (SEQ. ID. No. 321)
/5AmMC6/CAATCAGCTAATGACACTGCCT (SEQ. ID. No. 322)
/5AmMC6/GCTCTAAAGGGAAGCGCCTTC (SEQ. ID. No. 323)
/5AmMC6/GCAATCAGCTAACTACACTGCCT (SEQ. ID. No. 324)
/5AmMC6/AGAGAAAGTGCTTCCCTCTAGAG (SEQ. ID. No. 325)
/5AmMC6/CTACCTGCACGAACAGCACTTTG (SEQ. ID. No. 326)
/5AmMC6/TCCTCTAAAGAGAAGCGCTTT (SEQ. ID. No. 327)
/5AmMC6/TGCTCAATAAATACCCGTTGAA (SEQ. ID. No. 328)
/5AmMC6/CAGAAAGTGCTTCCCTCCAGAGA (SEQ. ID. No. 329)
/5AmMC6/AGCAAGCCCAGACCGCAAAAAG (SEQ. ID. No. 330)
/5AmMC6/CACTCTAAAGAGAAGCGCTTTG (SEQ. ID. No. 331)
/5AmMC6/AGAAAGGCAGCAGGTCGTATAG (SEQ. ID. No. 332)
/5AmMC6/GAGAAAGTGCTTCCCTTTGTAG (SEQ. ID. No. 333)
/5AmMC6/TACCTGCACTGTTAGCACTTTG (SEQ. ID. No. 334)
/5AmMC6/ACTCCAAAGGGAAGCGCCTTC (SEQ. ID. No. 335)
/5AmMC6/CACATAGGAATGAAAAGCCATA (SEQ. ID. No. 336)
/5AmMC6/AGACAGTGCTTCCATCTAGAGG (SEQ. ID. No. 337)
/5AmMC6/CCTCAAGGAGCCTCAGTCTAGT (SEQ. ID. No. 338)
/5AmMC6/CAGAAAGGGCTTCCCTTTGTAGA (SEQ. ID. No. 339)
/5AmMC6/ACAAGTGCCCTCACTGCAGT (SEQ. ID. No. 340)
/5AmMC6/AACCCACCAAAGAGAAGCACTTT (SEQ. ID. No. 341)
/5AmMC6/TAAACGGAACCACTAGTGACTTA (SEQ. ID. No. 342)
/5AmMC6/ACACTCTAAAGGGAAGCACTTTGT (SEQ. ID. No. 343)
/5AmMC6/AAAAAGTGCCCCCATAGTTTGAG (SEQ. ID. No. 344)
/5AmMC6/AACCCTCTGAAAGGAAGCACTT (SEQ. ID. No. 345)
/5AmMC6/GGCACACAAAGTGGAAGCACTTT (SEQ. ID. No. 346)
/5AmMC6/GCTCCAAAGGGAAGCGCTTTG (SEQ. ID. No. 347)
/5AmMC6/AGAGAGGGCCTCCACTTTGATG (SEQ. ID. No. 348)
/5AmMC6/AAAGGGCTTCCCTTTGCAGA (SEQ. ID. No. 349)
/5AmMC6/ACACTCAAAACCTGGCGGCACTT (SEQ. ID. No. 350)
/5AmMC6/ACACTCTAAAAGGATGCACGAT (SEQ. ID. No. 351)
/5AmMC6/CAAAAGAGCCCCCAGTTTGAGT (SEQ. ID. No. 352)
/5AmMC6/TTAAACATCACTGCAAGTCTTAA (SEQ. ID. No. 353)
/5AmMC6/ACACTACAAACTCTGCGGCACT (SEQ. ID. No. 354)
/5AmMC6/CAGAATCCTTGCCCAGGTGCAT (SEQ. ID. No. 355)
/5AmMC6/ACACACAAAAGGGAAGCACTTT (SEQ. ID. No. 356)
/5AmMC6/TCTCACCCAGGGACAAAGGATT (SEQ. ID. No. 357)
/5AmMC6/AGACTCAAAAGTAGTAGCACTTT (SEQ. ID. No. 358)
/5AmMC6/TAGCACCCAGATAGCAAGGAT (SEQ. ID. No. 359)
/5AmMC6/CATGCACATGCACACATACAT (SEQ. ID. No. 360)
/5AmMC6/CTGCAGAACTGTTCCCGCTGCTA (SEQ. ID. No. 361)
/5AmMC6/GGAAGAACAGCCCTCCTCTGCC (SEQ. ID. No. 362)
/5AmMC6/ATAGAGTGCAGAGCAGGGTCT (SEQ. ID. No. 363)
/5AmMC6/GAAGAGAGCTTGCCCTTGCATA (SEQ. ID. No. 364)
/5AmMC6/ATAAATGACACCTGCCTGTGAA (SEQ. ID. No. 365)
/5AmMC6/AGAGGTCGACCGTGTAATGTGC (SEQ. ID. No. 366)
/5AmMC6/TCTACTCAGAAGGGTGCCTTA (SEQ. ID. No. 367)
/5AmMC6/CCAGCAGCACCTGGGGCAGT (SEQ. ID. No. 368)
/5AmMC6/TTCACTCCAAAAGGTGCAAAA (SEQ. ID. No. 369)
/5AmMC6/ACACTTACTGAGCACCTACTAGG (SEQ. ID. No. 370)
/5AmMC6/TCTACTCCAAAAGGCTACAATCA (SEQ. ID. No. 371)
/5AmMC6/ACTGGAGGAAGGGCCCAGAGG (SEQ. ID. No. 372)
/5AmMC6/TCTACCCACAGACGTACCAATCA (SEQ. ID. No. 373)
/5AmMC6/ACGGAAGGGCAGAGAGGGCCAG (SEQ. ID. No. 374)
/5AmMC6/TGTGATTGCCACTCTCCTGAGTA (SEQ. ID. No. 375)
/5AmMC6/AAAAAGGTTAGCTGGGTGTGTT (SEQ. ID. No. 376)
/5AmMC6/CTACTCACAGAAGTGTCAAT (SEQ. ID. No. 377)
/5AmMC6/TTCTAGGATAGGCCCAGGGGC (SEQ. ID. No. 378)
/5AmMC6/TTCAATTTCTGCCGCAAAAG (SEQ. ID. No. 379)
/5AmMC6/AAAGGCATCATATAGGAGCTGAA (SEQ. ID. No. 380)
/5AmMC6/GCTATCTGCTGCAACAGAATTT (SEQ. ID. No. 381)
/5AmMC6/GGCTATAAAGTAACTGAGACGGA (SEQ. ID. No. 382)
/5AmMC6/GTGTGCTTACACACTTCCCGTTA (SEQ. ID. No. 383)
/5AmMC6/ACTGACCGACCGACCGATCGA (SEQ. ID. No. 384)
/5AmMC6/AGCACGTCACTTCCACTAAGA (SEQ. ID. No. 385)
/5AmMC6/ACAGTCAGGCTTTGGCTAGATCA (SEQ. ID. No. 386)
/5AmMC6/GCAAGGGCGAATGCAGAAAA (SEQ. ID. No. 387)
/5AmMC6/GCACTGGACTAGGGGTCAGCA (SEQ. ID. No. 388)
/5AmMC6/AACTCCGGGGCTGATCAGGT (SEQ. ID. No. 389)
/5AmMC6/AGAGGCAGGCACTCGGGCAGA (SEQ. ID. No. 390)
/5AmMC6/CTTGTACCAGTTATCTGCAA (SEQ. ID. No. 391)
/5AmMC6/CAATCAGCTAATTACACTGCCTA (SEQ. ID. No. 392)
/5AmMC6/TTGTACGTTTACATGGAGGTC (SEQ. ID. No. 393)
/5AmMC6/GTGAAAGTGTATGGGCTTTGTGAA (SEQ. ID. No. 394)
/5AmMC6/CTGACTGACTGACTGACTGACTG (SEQ. ID. No. 395)
/5AmMC6/CAGGCTCAAAGGGCTCCTCAGG (SEQ. ID. No. 396)
/5AmMC6/CCATAAAGTAGGAAACACTA (SEQ. ID. No. 397)
/5AmMC6/AACAAAATCACAAGTCTTCCA (SEQ. ID. No. 398)
/5AmMC6/TCACCGACAGCGTTGAATGT (SEQ. ID. No. 399)
/5AmMC6/TGTAAGTGCTCGTAATGCAGT (SEQ. ID. No. 400)
/5AmMC6/CGGGACTTTGAGGGCCAGT (SEQ. ID. No. 401)
/5AmMC6/ACCCTCATGCCCCTCAAGG (SEQ. ID. No. 402) /5AmMC6
GAATCCACCACGAACAACTT (SEQ. ID. No. 403)
/5AmMC6/AAAAGTAACTAGCACACCAC (SEQ. ID. No. 404)
/5AmMC6/AGAGACCGGTTCACTGTGA (SEQ. ID. No. 405)
/5AmMC6/ACATTTTTCGTTATTGCTCTT (SEQ. ID. No. 406)
/5AmMC6/AGAGACCGGTTCACTGTGA (SEQ. ID. No. 407)
/5AmMC6/TATGGCAGACTGTGATTTGTTG (SEQ. ID. No. 408)
/5AmMC6/CCTGATTCACAACACCAGCT (SEQ. ID. No. 409)
/5AmMC6/CATCGTTACCAGACAGTGTTA (SEQ. ID. No. 410)
/5AmMC6/GGATTCCTGGGAAAACTGGA (SEQ. ID. No. 411)
/5AmMC6/TCCACATGGAGTTGCTGTTACA (SEQ. ID. No. 412)
/5AmMC6/ACTGGTACAAGGGTTGGGAG (SEQ. ID. No. 413)
/5AmMC6/AACAGCTGCTTTTGGGATTCTG (SEQ. ID. No. 414)
/5AmMC6/CTGGGACTTTGTAGGCCAGT (SEQ. ID. No. 415)
/5AmMC6/ACCTAATATATCAAACATATCA (SEQ. ID. No. 416)
/5AmMC6/AGACTCCGGTGGAATGAAGG (SEQ. ID. No. 417)
/5AmMC6/AAGCCCAAAAGGAGAATTCTTTG (SEQ. ID. No. 418)
/5AmMC6/CAACATCAGTCTGATAAGCTA (SEQ. ID. No. 419)
/5AmMC6/AGGAACTGCCTTTCTCTCCAA (SEQ. ID. No. 420)
/5AmMC6/GTACAATCAACGGTCGATGG (SEQ. ID. No. 421)
/5AmMC6/ACCCTTATCAGTTCTCCGTCCA (SEQ. ID. No. 422)
/5AmMC6/AGAATTGCGTTTGGACAATC (SEQ. ID. No. 423)
/5AmMC6/TAGCTGGTTGAAGGGGACCAA (SEQ. ID. No. 424)
/5AmMC6/ACCCAGCAGACAATGTAGC (SEQ. ID. No. 425)
/5AmMC6/CCTCAAGGAGCTTCAGTCTAGT (SEQ. ID. No. 426)
/5AmMC6/ACCCAGTAGCCAGATGTAGC (SEQ. ID. No. 427)
/5AmMC6/CCAACAACAGGAAACTACCTA (SEQ. ID. No. 428)
/5AmMC6/GCCCTCTCAACCCAGCTTT (SEQ. ID. No. 429)
/5AmMC6/CCAGGTTCCACCCCAGCAGG (SEQ. ID. No. 430)
/5AmMC6/GCAATGCAACTACAATGCAC (SEQ. ID. No. 431)
/5AmMC6/ACACTCAAAAGATGGCGGCA (SEQ. ID. No. 432)
/5AmMC6/AACAAAATCACTGATGCTGG (SEQ. ID. No. 433)
/5AmMC6/ACGCTCAAATGTCGCAGCAC (SEQ. ID. No. 434)
/5AmMC6/GAGCTCCTGGAGGACAGGG (SEQ. ID. No. 435)
/5AmMC6/ACACCCCAAAATCGAAGCAC (SEQ. ID. No. 436)
/5AmMC6/GGGTGCGATTTCTGTGTGAG (SEQ. ID. No. 437)
/5AmMC6/GGAAAGCGCCCCCATTTTGA (SEQ. ID. No. 438)
/5AmMC6/ACTCAGTAATGGTAACGGTT (SEQ. ID. No. 439)
/5AmMC6/CACTTATCAGGTTGTATTATAA (SEQ. ID. No. 440)
/5AmMC6/GAGGAAACCAGCAAGTGTTG (SEQ. ID. No. 441)
/5AmMC6/GTCTGTCAAATCATAGGTCAT (SEQ. ID. No. 442)
/5AmMC6/GCAATGCAACAGCAATGCAC (SEQ. ID. No. 443)
/5AmMC6/GGGGTTCACCGAGCAACATTC (SEQ. ID. No. 444)
/5AmMC6/GTCCGTGGTTCTACCCTGTGG (SEQ. ID. No. 445)
/5AmMC6/CAGGCCATCTGTGTTATATT (SEQ. ID. No. 446)
/5AmMC6/ATACTAGACTGTGAGCTCCTCGA (SEQ. ID. No. 447)
/5AmMC6/AGTGGATGTTCCTCTATGAT (SEQ. ID. No. 448)
/5AmMC6/CCAGAAGGAGCACTTAGGGCAG (SEQ. ID. No. 449)
/5AmMC6/CGTGGATTTTCCTCTACGAT (SEQ. ID. No. 450)
/5AmMC6/GCTGGATGCAAACCTGCAAAAC (SEQ. ID. No. 451)
/5AmMC6/GAGGGTTAGTGGACCGTGTT (SEQ. ID. No. 452)
/5AmMC6/AATCCCATCCCCAGGAACCC (SEQ. ID. No. 453)
/5AmMC6/GATGTGGACCATACTACATA (SEQ. ID. No. 454)
/5AmMC6/CGGCTCTGTCGTCGAGGCGC (SEQ. ID. No. 455)
/5AmMC6/GGCTAGTGGACCAGGTGAAG (SEQ. ID. No. 456)
/5AmMC6/AAAGTCTCGCTCTCTGCCCCT (SEQ. ID. No. 457)
/5AmMC6/CAGAACTTAGCCACTGTGAA (SEQ. ID. No. 458)
/5AmMC6/TCAACGGGAGTGATCGTGTCAT (SEQ. ID. No. 459)
/5AmMC6/AGCCTATCCTGGATTACTTGAA (SEQ. ID. No. 460)
/5AmMC6/AGCATTGCAACCGATCCCAAC (SEQ. ID. No. 461)
/5AmMC6/CTGTTCCTGCTGAACTGAGCCA (SEQ. ID. No. 462)
/5AmMC6/GCAGCAAACATCTGACTGAAAG (SEQ. ID. No. 463)
TABLE-US-00009 TABLE 5 miRNA detection probes ProbeID: Unique
identifier for each probe sequence. Annotation: miRNAs recognized
by the probe, based on miRBASE release 7.0. "h" stands for human,
"m" for mouse and "r" for rat. Sequence: sequence of probe.
/5AmMC6/ indicates 5' amino modification. Probe Annotation Sequence
EAM 190 h-miR-1 9b_rfam7.0 /5AmMC6/ACAAATTCGGTTCTACAGGGTA (SEQ. ID.
No. 464) EAM 187 hmr-miR-1 07_rfam7.0
/5AmMC6/TGATAGCCCTGTACAATGCTGCT (SEQ. ID. No. 465) EAM 185
hmr-miR-1 03_rfam7.0 /5AmMC6/TCATAGCCCTGTACAATGCTGCT (SEQ. ID. No.
466) EAM 181 hmr-let-7f_rfam7.0 /5AmMC6/AACTATACAATCTACTACCTCA
(SEQ. ID. No. 467) EAM 179 hmr-let-7d_rfam7.0
/5AmMC6/ACTATGCAACCTACTACCTCT (SEQ. ID. No. 468) EAM 177 mr-miR-1
01 b_rfam7.0 /5AmMC6/TTCAGCTATCACAGTACTGTA (SEQ. ID. No. 469) EAM
175 hmr-miR-320_rfam7.0 /5AmMC6/TCGCCCTCTCAACCCAGCTTTT (SEQ. ID.
No. 470) EAM 168 hmr-let-7e_rfam7.0 /5AmMC6/CTATACAACCTCCTACCTCA
(SEQ. ID. No. 471) EAM 161 hmr-miR-28_rfam7.0
/5AmMC6/CTCAATAGACTGTGAGCTCCTT (SEQ. ID. No. 472) EAM 160
hmr-miR-26b_rfam7.0 /5AmMC6/AACCTATCCTGAATTACTTGAA (SEQ. ID. No.
473) EAM 155 hmr-miR-1 36_rfam7.0 /5AmMC6/TCCATCATCAAAACAAATGGAGT
(SEQ. ID. No. 474) EAM283 mr-miR-21 1_rfam7.0
/5AmMC6/AGGCAAAGGATGACAAAGGGAA (SEQ. ID. No. 475) EAM282 m-miR-1
99b_rfam7.0 /5AmMC6/GAACAGGTAGTCTAAACACTGGG (SEQ. ID. No. 476)
EAM281 mr-miR-21 7_rfam7.0 /5AmMC6/ATCCAGTCAGTTCCTGATGCAGTA (SEQ.
ID. No. 477) EAM280 hmr-miR-30a-3p rfam7.0
/5AmMC6/GCTGCAAACATCCGACTGAAAG (SEQ. ID. No. 478) EAM279
hmr-miR-29c_rfam7.0 /5AmMC6/TAACCGATTTCAAATGGTGCTA (SEQ. ID. No.
479) EAM278 hmr-miR-98_rfam7.0 /5AmMC6/AACAATACAACTTACTACCTCA (SEQ.
ID. No. 480) EAM238 hm-miR-1_rfam7.0 /5AmMC6/ATACATACTTCTTTACATTCCA
(SEQ. ID. No. 481) EAM270 hmr-miR-30b_rfam7.0
/5AmMC6/GCTGAGTGTAGGATGTTTACA (SEQ. ID. No. 482) EAM 159 hmr-miR-1
30a rfam7.0 /5AmMC6/ATGCCCTTTTAACATTGCACTG (SEQ. ID. No. 483) EAM
163 hmr-miR-1 42-3p_rfam7.0 /5AmMC6ITCCATAAAGTAGGAAACACTACA (SEQ.
ID. No. 484) EAM 171 hmr-miR-1 37_rfam7.0
/5AmMC6/CTACGCGTATTCTTAAGCAATAA (SEQ. ID. No. 485) EAM306
m-miR-201_rfam7.0 /5AmMC6/AGAACAATGCCTTACTGAGTA (SEQ. ID. No. 486)
EAM307 m-miR-202_rfam7.0 /5AmMC6/TCTTCCCATGCGCTATACCTCT (SEQ. ID.
No. 487) EAM308 hmr-miR-206_rfam7.0 /5AmMC6/CCACACACTTCCTTACATTCCA
(SEQ. ID. No. 488) EAM309 m-miR-207_rfam7.0
/5AmMC6/GAGGGAGGAGAGCCAGGAGAAGC (SEQ. ID. No. 489) EAM31 0
hmr-miR-208_rfam7.0 /5AmMC6/ACAAGCTTTTTGCTCGTCTTAT (SEQ. ID. No.
490) EAM247 hmr-miR-21 2_rfam7.0 /5AmMC6/GGCCGTGACTGGAGACTGTTA
(SEQ. ID. No. 491) EAM251 hmr-miR-21 6_rfam7.0
/5AmMC6/CACAGTTGCCAGCTGAGATTA (SEQ. ID. No. 492) EAM253 hmr-miR-21
8_rfam7.0 /5AmMC6/ACATGGTTAGATCAAGCACAA (SEQ. ID. No. 493) EAM275
hmr-miR-34a_rfam7.0 /5AmMC6/ACAACCAGCTAAGACACTGCCA (SEQ. ID. No.
494) EAM246 h-miR-21 1 _rfam7.0 /5AmMC6/AGGCGAAGGATGACAAAGGGAA
(SEQ. ID. No. 495) EAM250 h-miR-21 5_rfam7.0
/5AmMC6/GTCTGTCAATTCATAGGTCAT (SEQ. ID. No. 496) EAM252 h-miR-21
7_rfam7.0 /5AmMC6/ATCCAATCAGTTCCTGATGCAGTA (SEQ. ID. No. 497)
EAM224 hmr-miR-1 7-5p_rfam7.0 /5AmMC6/ACTACCTGCACTGTAAGCACTTTG
(SEQ. ID. No. 498) EAM225 hmr-miR-1 8a_rfam7.0
/5AmMC6/TATCTGCACTAGATGCACCTTA (SEQ. ID. No. 499) EAM226 hmr-miR-1
81 a_rfam7.0 /5AmMC6/ACTCACCGACAGCGTTGAATGTT (SEQ. ID. No. 500)
EAM227 hmr-miR-1 81 b_rfam7.0 /5AmMC6/AACCCACCGACAGCAATGAATGTT
(SEQ. ID. No. 501) EAM234 hmr-miR-1 99a_rfam7.0
/5AmMC6/GAACAGGTAGTCTGAACACTGGG (SEQ. ID. No. 502) EAM235 h-miR-1
99b_rfam7.0 /5AmMC6/GAACAGATAGTCTAAACACTGGG (SEQ. ID. No. 503)
EAM236 hmr-miR-1 9a_rfam7.0 /5AmMC6/TCAGTTTTGCATAGATTTGCACA (SEQ.
ID. No. 504) EAM241 hmr-miR-203 rfam7.0
/5AmMC6/CTAGTGGTCCTAAACATTTCAC (SEQ. ID. No. 505) EAM242
hmr-miR-204_rfam7.0 /5AmMC6/AGGCATAGGATGACAAAGGGAA (SEQ. ID. No.
506) EAM243 hmr-miR-205_rfam7.0 /5AmMC6/CAGACTCCGGTGGAATGAAGGA
(SEQ. ID. No. 507) EAM245 hmr-miR-21 0_rfam7.0
/5AmMC6/CAGCCGCTGTCACACGCACAG (SEQ. ID. No. 508) EAM249 hmr-miR-21
4_rfam7.0 /5AmMC6/CTGCCTGTCTGTGCCTGCTGT (SEQ. ID. No. 509) EAM 184
hmr-miR-1 00 rfam7.0 /5AmMC6/CACAAGTTCGGATCTACGGGTT (SEQ. ID. No.
510) EAM 186 h-miR-1 06a_rfam7.0 /5AmMC6/GCTACCTGCACTGTAAGCACTTTT
(SEQ. ID. No. 511) EAM 189 hmr-miR-1 0a_rfam7.0
/5AmMC6/CACAAATTCGGATCTACAGGGTA (SEQ. ID. No. 512) EAM 191
hmr-miR-1 22a_rfam7.0 /5AmMC6/ACAAACACCATTGTCACACTCCA (SEQ. ID. No.
513) EAM 192 hmr-miR-1 26*_rfam7.0 /5AmMC6/CGCGTACCAAAAGTAATAATG
(SEQ. ID. No. 514) EAM 198 hmr-miR-1 30b_rfam7.0
/5AmMC6/GCCCTTTCATCATTGCACTG (SEQ. ID. No. 515) EAM202 hmr-miR-1 34
_fam7.0 /5AmMC6/TCCCTCTGGTCAACCAGTCACA (SEQ. ID. No. 516) EAM209
hmr-miR-1 42-5p_rfam7.0 /5AmMC6/GTAGTGCTTTCTACTTTATG (SEQ. ID. No.
517) EAM221 m-miR-1 55_rfam7.0 /5AmMC6/CCCCTATCACAATTAGCATTAA (SEQ.
ID. No. 518) EAM223 hmr-miR-1 5b_rfam7.0
/5AmMC6/TGTAAACCATGATGTGCTGCTA (SEQ. ID. No. 519) EAM228 hmr-miR-1
81 c_rfam7.0 /5AmMC6/ACTCACCGACAGGTTGAATGTT (SEQ. ID. No. 520)
EAM222 hm-miR-1 5a_rfam7.0 /5AmMC6/CACAAACCATTATGTGCTGCTA (SEQ. ID.
No. 521) EAM 111 hm-let-7g_rfam7.0 /5AmMC6/TAACTGTACAAACTACTACCTCA
(SEQ. ID. No. 522) EAM 131 hmr-miR-92_rfam7.0
/5AmMC6/ACAGGCCGGGACAAGTGCAATAT (SEQ. ID. No. S23) EAM 139
hmr-miR-1 46a_rfam7.0 /5AmMC6/TAACCCATGGAATTCAGTTCTCA (SEQ. ID. No.
524) EAM 145 hmr-let-7c_rfam7.0 /5AmMC6/AACCATACAACCTACTACCTCA
(SEQ. ID. No. 525) EAM 109 hmr-miR-7_rfam7.0
/5AmMC6/AACAACAAAATCACTAGTCTTCCA (SEQ. ID. No. 526) EAM 152
hm-miR-9*_rfam7.0 /5AmMC6/ACTTTCGGTTATCTAGCTTTAT (SEQ. ID. No. 527)
J LA21 5 hmr-let-7i_rfam7.0 /5AmMC6/ACAGCACAAACTACTACCTCA (SEQ. ID.
No. 528) EAM 153 hmr-let-7a rfam7.0 /5AmMC6/AACTATACAACGTACTACCTCA
(SEQ. ID. No. 529) EAM 147 hmr-let-7b_rfam7.0
/5AmMC6/AACCACACAACCTACTACCTCA (SEQ. ID. No. 530) EAM 137 hmr-miR-1
32_rfam7.0 /5AmMC6/CCGACCATGGCTGTAGACTGTTA (SEQ. ID. No. 531) EAM
133 hmr-miR-324-5p_rfam7.0 /5AmMC6/ACACCAATGCCCTAGGGGATGCG (SEQ.
ID. No. 532) EAM 103 hmr-miR-1 24a_rfam7.0
/5AmMC6/TGGCATTCACCGCGTGCCTTA (SEQ. ID. No. 533) EAM 105 hmr-miR-1
25b rfam7.0 /5AmMC6/TCACAAGTTAGGGTCTCAGGGA (SEQ. ID. No. 534) EAM
121 hmr-miR-99a_rfam7.0 /5AmMC6/CACAAGATCGGATCTACGGGT (SEQ. ID. No.
535) EAM 115 hmr-miR-1 6_rfam7.0 /5AmMC6/CGCCAATATTTACGTGCTGCTA
(SEQ. ID. No. 536) EAM 119 hmr-miR-29b_rfam7.0
/5AmMC6/AACACTGATTTCAAATGGTGCTA (SEQ. ID. No. 537) EAM31 1
hmr-miR-1 01_rfam7.0 /5AmMC6/CTTCAGTTATCACAGTACTGTA (SEQ. ID. No.
538) EAM31 2 h-miR-1 05_rfam7.0 /5AmMC6/ACAGGAGTCTGAGCATTTGA (SEQ.
ID. No. 539) EAM31 3 hmr-miR-1 06b_rfam7.0
/5AmMC6/ATCTGCACTGTCAGCACTTTA (SEQ. ID. No. 540) EAM31 4 hmr-miR-1
26_rfam7.0 /5AmMC6/GCATTATTACTCACGGTACGA (SEQ. ID. No. 541) EAM31 5
hmr-miR-1 27_rfam7.0 /5AmMC6/AGCCAAGCTCAGACGGATCCGA (SEQ. ID. No.
542) EAM320 hm-miR-1 89_rfam7.0 /5AmMC6/ACTGATATCAGCTCAGTAGGCAC
(SEQ. ID. No. 543) J LA21 6 hmr-miR-200c_rfam7.0
/5AmMC6/TCCATCATTACCCGGCAGTATTA (SEQ. ID. No. 544)
EAM323 h-miR-224_rfam7.0 /5AmMC6/TAAACGGAACCACTAGTGACTTG (SEQ. ID.
No. 545) EAM324 hmr-miR-25_rfam7.0 /5AmMC6/TCAGACCGAGACAAGTGCAATG
(SEQ. ID. No. 546) EAM386 r-miR-336_rfam7.0
/5AmMC6/AGACTAGATATGGAAGGGTGA (SEQ. ID. No. 547) J LA21 8
r-miR-343_rfam7.0 /5AmMC6/TCTGGGCACACGGAGGGAGA (SEQ. ID. No. 548)
EAM388 r-miR-344_rfam7.0 /5AmMC6/ACGGTCAGGCTTTGGCTAGAT (SEQ. ID.
No. 549) EAM338 h-miR-95_rfam7.0 /5AmMC6/TGCTCAATAAATACCCGTTGAA
(SEQ. ID. No. 550) J LA21 4 hmr-miR-1 29_rfam7.0
/5AmMC6/AGCAAGCCCAGACCGCAAAAAG (SEQ. ID. No. 551) EAM340
mr-let-7d*_rfam7.0 /5AmMC6/AGAAAGGCAGCAGGTCGTATAG (SEQ. ID. No.
552) EAM341 m-miR-1 06a_rfam7.0 /5AmMC6/TACCTGCACTGTTAGCACTTTG
(SEQ. ID. No. 553) EAM342 hmr-miR-1 35b_rfam7.0
/5AmMC6/CACATAGGAATGAAAAGCCATA (SEQ. ID. No. 554) EAM343 mr-mi R-1
51 rfam7.0 /5AmMC6/CCTCAAGGAGCCTCAGTCTAGT (SEQ. ID. No. 555) EAM344
m-miR-1 7-3p_rfam7.0 /5AmMC6/ACAAGTGCCCTCACTGCAGT (SEQ. ID. No.
556) EAM345 m-miR-224_rfam7.0 /5AmMC6/TAAACGGAACCACTAGTGACTTA (SEQ.
ID. No. 557) EAM346 mr-mi R-290_rfam7.0
/5AmMC6/AAAAAGTGCCCCCATAGTTTGAG (SEQ. ID. No. 558) EAM347
mr-miR-291 -3p_rfam7.0 /5AmMC6/GGCACACAAAGTGGAAGCACTTT (SEQ. ID.
No. 559) EAM348 mr-miR-291 -5p rfam7.0
/5AmMC6/AGAGAGGGCCTCCACTTTGATG (SEQ. ID. No. 560) EAM349
mr-miR-292-3p_rfam7.0 /5AmMC6/ACACTCAAAACCTGGCGGCACTT (SEQ. ID. No.
561) EAM350 mr-miR-292-5p_rfam7.0 /5AmMC6/CAAAAGAGCCCCCAGTTTGAGT
(SEQ. ID. No. 562) EAM351 m-miR-293_rfam7.0
/5AmMC6/ACACTACAAACTCTGCGGCACT (SEQ. ID. No. 563) EAM352
m-miR-294_rfam7.0 /5AmMC6/ACACACAAAAGGGAAGCACTTT (SEQ. ID. No. 564)
EAM353 m-miR-295_rfam7.0 /5AmMC6/AGACTCAAAAGTAGTAGCACTTT (SEQ. ID.
No. 565) EAM354 m-miR-297_rfam7.0 /5AmMC6/CATGCACATGCACACATACAT
(SEQ. ID. No. 566) EAM355 mr-mi R-298_rfam7.0
/5AmMC6/GGAAGAACAGCCCTCCTCTGCC (SEQ. ID. No. 567) EAM356 mr-mi
R-300_rfam7.0 /5AmMC6/GAAGAGAGCTTGCCCTTGCATA (SEQ. ID. No. 568)
EAM358 hmr-miR-323_rfam7.0 /5AmMC6/AGAGGTCGACCGTGTAATGTGC (SEQ. ID.
No. 569) EAM359 hmr-miR-324-3p_rfam7.0 /5AmMC6/CCAGCAGCACCTGGGGCAGT
(SEQ. ID. No. 570) EAM360 mr-mi R-325_rfam7.0
/5AmMC6/ACACTTACTGAGCACCTACTAGG (SEQ. ID. No. 571) EAM361
hmr-miR-326_rfam7.0 /5AmMC6/ACTGGAGGAAGGGCCCAGAGG (SEQ. ID. No.
572) EAM362 hmr-miR-328_rfam7.0 /5AmMC6/ACGGAAGGGCAGAGAGGGCCAG
(SEQ. ID. No. 573) EAM363 mr-mi R-329_rfam7.0
/5AmMC6/AAAAAGGTTAGCTGGGTGTGTT (SEQ. ID. No. 574) EAM365
hmr-miR-331_rfam7.0 /5AmMC6/TTCTAGGATAGGCCCAGGGGC (SEQ. ID. No.
575) EAM366 mr-mi R-337_rfam7.0 /5AmMC6/AAAGGCATCATATAGGAGCTGAA
(SEQ. ID. No. 576) EAM367 hmr-miR-338_rfam7.0
/5AmMC6/TCAACAAAATCACTGATGCTGGA (SEQ. ID. No. 577) EAM368
hmr-miR-339_rfam7.0 /5AmMC6/TGAGCTCCTGGAGGACAGGGA (SEQ. ID. No.
578) EAM369 hmr-miR-340_rfam7.0 /5AmMC6/GGCTATAAAGTAACTGAGACGGA
(SEQ. ID. No. 579) EAM370 mr-mi R-341_rfam7.0
/5AmMC6/ACTGACCGACCGACCGATCGA (SEQ. ID. No. 580) EAM371
hmr-miR-342_rfam7.0 /5AmMC6/GACGGGTGCGATTTCTGTGTGAGA (SEQ. ID. No.
581) EAM372 m-miR-344_rfam7.0 /5AmMC6/ACAGTCAGGCTTTGGCTAGATCA (SEQ.
ID. No. 582) EAM373 mr-miR-345_rfam7.0
/5AmMC6/GCACTGGACTAGGGGTCAGCA (SEQ. ID. No. 583) EAM374 m-miR-346
rfam7.0 /5AmMC6/AGAGGCAGGCACTCGGGCAGA (SEQ. ID. No. 584) EAM375
mr-mi R-34b_rfam7.0 /5AmMC6/CAATCAGCTAATTACACTGCCTA (SEQ. ID. No.
585) J LA21 7 mr-mi R-350_rfam7.0 /5AmMC6/GTGAAAGTGTATGGGCTTTGTGAA
(SEQ. ID. No. 586) EAM377 mr-miR-351_rfam7.0
/5AmMC6/CAGGCTCAAAGGGCTCCTCAGG (SEQ. ID. No. 587) EAM378 mr-mi
R-7b_rfam7.0 /5AmMC6/AACAAAATCACAAGTCTTCCA (SEQ. ID. No. 588)
EAM382 r-miR-20*_rfam7.0 /5AmMC6/TGTAAGTGCTCGTAATGCAGT (SEQ. ID.
No. 589) EAM383 r-miR-327_rfam7.0 /5AmMC6/ACCCTCATGCCCCTCAAGG (SEQ.
ID. No. 590) EAM384 r-miR-333_rfam7.0 /5AmMC6/AAAAGTAACTAGCACACCAC
(SEQ. ID. No. 591) EAM385 hmr-miR-335_rfam7.0
/5AmMC6/ACATTTTTCGTTATTGCTCTT (SEQ. ID. No. 592) EAM393
r-miR-7*_rfam7.0 /5AmMC6/TATGGCAGACTGTGATTTGTTG (SEQ. ID. No. 593)
EAM304 hmr-miR-200a_rfam7.0 /5AmMC6/CATCGTTACCAGACAGTGTTA (SEQ. ID.
No. 594) EAM298 hmr-miR-1 94_rfam7.0 /5AmMC6/TCCACATGGAGTTGCTGTTACA
(SEQ. ID. No. 595) J LA221 hmr-miR-1 91_rfam7.0
/5AmMC6/AACAGCTGCTTTTGGGATTCTG (SEQ. ID. No. 596) EAM295 hmr-miR-1
90_rfam7.0 /5AmMC6/ACCTAATATATCAAACATATCA (SEQ. ID. No. 597) EAM292
hmr-miR-1 86_rfam7.0 /5AmMC6/AAGCCCAAAAGGAGAATTCTTTG (SEQ. ID. No.
598) J LA21 9 hmr-miR-1 85_rfam7.0 /5AmMC6/AGGAACTGCCTTTCTCTCCAA
(SEQ. ID. No. 599) EAM290 hmr-miR-1 84_rfam7.0
/5AmMC6/ACCCTTATCAGTTCTCCGTCCA (SEQ. ID. No. 600) EAM402 hm-miR-1
33b_rfam7.0 /5AmMC6/TAGCTGGTTGAAGGGGACCAA (SEQ. ID. No. 601) EAM403
h-miR-1 51_rfam7.0 /5AmMC6/CCTCAAGGAGCTTCAGTCTAGT (SEQ. ID. No.
602) EAM404 hmr-miR-1 96b_rfam7.0 /5AmMC6/CCAACAACAGGAAACTACCTA
(SEQ. ID. No. 603) EAM41 8 hm-miR-370_rfam7.0
/5AmMC6/CCAGGTTCCACCCCAGCAGG (SEQ. ID. No. 604) EAM41 9 h-miR-37 1
rfam7.0 /5AmMC6/ACACTCAAAAGATGGCGGCA (SEQ. ID. No. 605) EAM420
h-miR-372_rfam7.0 /5AmMC6/ACGCTCAAATGTCGCAGCAC (SEQ. ID. No. 606)
EAM421 h-miR-373_rfam7.0 /5AmMC6/ACACCCCAAAATCGAAGCAC (SEQ. ID. No.
607) EAM422 h-miR-373*_rfam7.0 /5AmMC6/GGAAAGCGCCCCCATTTTGA (SEQ.
ID. No. 608) EAM423 h-miR-374_rfam7.0
/5AmMC6/CACTTATCAGGTTGTATTATAA (SEQ. ID. No. 609) EAM426 m-miR-21 5
rfam7.0 /5AmMC6/GTCTGTCAAATCATAGGTCAT (SEQ. ID. No. 610) EAM427
hm-miR-409-3p_rfam7.0 /5AmMC6/GGGGTTCACCGAGCAACATTC (SEQ. ID. No.
611) EAM428 hm-miR-41 0_rfam7.0 /5AmMC6/CAGGCCATCTGTGTTATATT (SEQ.
ID. No. 612) EAM429 m-miR-376b_rfam7.0 /5AmMC6/AGTGGATGTTCCTCTATGAT
(SEQ. ID. No. 613) EAM430 m-miR-376a_rfam7.0
/5AmMC6/CGTGGATTTTCCTCTACGAT (SEQ. ID. No. 614) EAM431 m-miR-41 1
_rfam7.0 /5AmMC6/GAGGGTTAGTGGACCGTGTT (SEQ. ID. No. 615) EAM432
m-miR-380-3p_rfam7.0 /5AmMC6/GATGTGGAGGATACTACATA (SEQ. ID. No.
616) EAM433 hm-miR-41 2_rfam7.0 /5AmMC6/GGCTAGTGGACCAGGTGAAG (SEQ.
ID. No. 617) EAM264 hmr-miR-27b_rfam7.0
/5AmMC6/CAGAACTTAGCCACTGTGAA (SEQ. ID. No. 618) EAM263
hmr-miR-26a_rfam7.0 /5AmMC6/AGCCTATCCTGGATTACTTGAA (SEQ. ID. No.
619) EAM262 hmr-miR-24_rfam7.0 /5AmMC6/CTGTTCCTGCTGAACTGAGCCA (SEQ.
ID. No. 620) EAM261 hmr-miR-23b_rfam7.0
/5AmMC6/GTGGTAATCCCTGGCAATGTGAT (SEQ. ID. No. 621) EAM260
hmr-miR-23a_rfam7.0 /5AmMC6/GGAAATCCCTGGCAATGTGAT (SEQ. ID. No.
622) EAM256 h-miR-220_rfam7.0 /5AmMC6/AAAGTGTCAGATACGGTGTGG (SEQ.
ID. No. 623) EAM255 hmr-miR-22_rfam7.0
/5AmMC6/ACAGTTCTTCAACTGGCAGCTT (SEQ. ID. No. 624) EAM248 hmr-miR-21
3_rfam7.0 /5AmMC6/GGTACAATCAACGGTCGATGGT (SEQ. ID. No. 625) EAM244
hmr-miR-21_rfam7.0 /5AmMC6/TCAACATCAGTCTGATAAGCTA (SEQ. ID. No.
626) EAM240 hmr-miR-20a_rfam7.0 /5AmMC6/CTACCTGCACTATAAGCACTTTA
(SEQ. ID. No. 627) EAM237 hmr-miR-1 9b_rfam7.0
/5AmMC6/TCAGTTTTGCATGGATTTGCACA (SEQ. ID. No. 628) EAM233 hmr-miR-1
96a rfam7.0 /5AmMC6/CCCAACAACATGAAACTACCTA (SEQ. ID. No. 629) EAM21
4 hm-miR-1 48a_rfam7.0 /5AmMC6/ACAAAGTTCTGTAGTGCACTGA (SEQ. ID. No.
630) EAM21 2 hmr-miR-1 45_rfam7.0 /5AmMC6/AAGGGATTCCTGGGAAAACTGGAC
(SEQ. ID. No. 631) EAM21 1 hmr-miR-1 44_rfam7.0
/5AmMC6/CTAGTACATCATCTATACTGTA (SEQ. ID. No. 632) EAM21 0 hmr-miR-1
43_rfam7.0 /5AmMC6/tgAGCTACAGTGCUCATCTCA (SEQ. ID. No.
633) EAM389 r-miR-346 rfam7.0 /5AmMC6/AGAGGCAGGCACTCAGGCAGA (SEQ.
ID. No. 634) EAM390 r-miR-347_rfam7.0 /5AmMC6/TGGGCGACCCAGAGGGACA
(SEQ. ID. No. 635) EAM391 r-miR-349_rfam7.0
/5AmMC6/AGAGGTTAAGACAGCAGGGCTG (SEQ. ID. No. 636) J LA223
hmr-miR-33_rfam7.0 /5AmMC6/TGCAATGCAACTACAATGCACC (SEQ. ID. No.
637) EAM277 hmr-miR-96_rfam7.0 /5AmMC6/GCAAAAATGTGCTAGTGCCAAA (SEQ.
ID. No. 638) EAM276 hmr-miR-9_rfam7.0
/5AmMC6/TCATACAGCTAGATAAGCAAAGA (SEQ. ID. No. 639) EAM272
hmr-miR-30d_rfam7.0 /5AmMC6/CTTCCAGTCGGGGATGTTTACA (SEQ. ID. No.
640) EAM288 mr-mi R-1 0b_rfam7.0 /5AmMC6/ACACAAATTCGGTTCTACAGGG
(SEQ. ID. No. 641) EAM293 hm-miR-1 88_rfam7.0
/5AmMC6/ACCCTCCACCATGCAAGGGATG (SEQ. ID. No. 642) EAM297 hmr-miR-1
93a_rfam7.0 /5AmMC6/CTGGGACTTTGTAGGCCAGTT (SEQ. ID. No. 643) EAM301
h-miR-1 98_rfam7.0 /5AmMC6/CCTATCTCCCCTCTGGACC (SEQ. ID. No. 644)
EAM232 hmr-miR-1 92_rfam7.0 /5AmMC6/GGCTGTCAATTCATAGGTCAG (SEQ. ID.
No. 645) EAM231 hmr-miR-1 87_rfam7.0 /5AmMC6/CGGCTGCAACACAAGACACGA
(SEQ. ID. No. 646) EAM230 hmr-miR-1 83_rfam7.0
/5AmMC6/CAGTGAATTCTACCAGTGCCATA (SEQ. ID. No. 647) EAM229 hm-miR-1
82_rfam7.0 /5AmMC6/TGTGAGTTCTACCATTGCCAAA (SEQ. ID. No. 648) EAM220
hmr-miR-1 54_rfam7.0 /5AmMC6/CGAAGGCAACACGGATAACCTA (SEQ. ID. No.
649) EAM21 9 hmr-miR-1 53_rfam7.0 /5AmMC6/TCACTTTTGTGACTATGCAA
(SEQ. ID. No. 650) EAM21 8 hmr-miR-1 52_rfam7.0
/5AmMC6/CCAAGTTCTGTCATGCACTGA (SEQ. ID. No. 651) EAM21 7 hmr-miR-1
50_rfam7.0 /5AmMC6/ACACTGGTACAAGGGTTGGGAGA (SEQ. ID. No. 652) EAM21
6 hm-miR-1 49_rfam7.0 /5AmMC6/GGAGTGAAGACACGGAGCCAGA (SEQ. ID. No.
653) EAM21 5 hmr-miR-1 48b_rfam7.0 /5AmMC6/ACAAAGTTCTGTGATGCACTGA
(SEQ. ID. No. 654) EAM271 hmr-miR-30c rfam7.0
/5AmMC6/GCTGAGAGTGTAGGATGTTTACA (SEQ. ID. No. 655) EAM268
hmr-miR-29a_rfam7.0 /5AmMC6/AACCGATTTCAGATGGTGCTAG (SEQ. ID. No.
656) EAM305 hmr-miR-200b_rfam7.0 /5AmMC6/GTCATCATTACCAGGCAGTATTA
(SEQ. ID. No. 657) EAM303 hm-miR-1 99a*_rfam7.0
/5AmMC6/AACCAATGTGCAGACTACTGTA (SEQ. ID. No. 658) EAM300 h-miR-1
97_rfam7.0 /5AmMC6/GCTGGGTGGAGAAGGTGGTGAA (SEQ. ID. No. 659) EAM299
hmr-miR-1 95 rfam7.0 /5AmMC6/GCCAATATTTCTGTGCTGCTA (SEQ. ID. No.
660) J LA91 hmr-miR-99b_rfam7.0 /5AmMC6/CGCAAGGTCGGTTCTACGGGTG
(SEQ. ID. No. 661) J LA92 hmr-miR-433_rfam7.0
/5AmMC6/ACACCGAGGAGCCCATCATGAT (SEQ. ID. No. 662) J LA93
hmr-miR-431_rfam7.0 /5AmMC6/CCTGCATGACGGCCTGCAAGACA (SEQ. ID. No.
663) J LA94 hmr-miR-365_rfam7.0 /5AmMC6/ATAAGGATTTTTAGGGGCATTA
(SEQ. ID. No. 664) J LA95 hmr-miR-450_rfam7.0
/5AmMC6/TATTAGGAACACATCGCAAAAA (SEQ. ID. No. 665) J LA96
hmr-miR-449_rfam7.0 /5AmMC6/ACCAGCTAACAATACACTGCCA (SEQ. ID. No.
666) J LA99 hmr-miR-448_rfam7.0 /5AmMC6/ATGGGACATCCTACATATGCAA
(SEQ. ID. No. 667) J LA1 03 hmr-miR-424_rfam7.0
/5AmMC6/TTCAAAACATGAATTGCTGCTG (SEQ. ID. No. 668) J LA1 05
hm-miR-36 1_rfam7.0 /5AmMC6/GTACCCCTGGAGATTCTGATAA (SEQ. ID. No.
669) J LA1 06 hm-miR-375_rfam7.0 /5AmMC6/TCACGCGAGCCGAACGAACAAA
(SEQ. ID. No. 670) J LA1 07 hm-miR-377_rfam7.0
/5AmMC6/ACAAAAGTTGCCTTTGTGTGAT (SEQ. ID. No. 671) J LA1 08
hm-miR-378_rfam7.0 /5AmMC6/ACACAGGACCTGGAGTCAGGAG (SEQ. ID. No.
672) J LA1 09 hm-miR-379_rfam7.0 /5AmMC6/CCTACGTTCCATAGTCTACCA
(SEQ. ID. No. 673) J LA1 10 hm-miR-380-5p_rfam7.0
/5AmMC6/GCGCATGTTCTATGGTCAACCA (SEQ. ID. No. 674) J LA1 11
hm-miR-38 1_rfam7.0 /5AmMC6/ACAGAGAGCTTGCCCTTGTATA (SEQ. ID. No.
675) J LA1 12 hm-miR-382_rfam7.0 /5AmMC6/CGAATCCACCACGAACAACTTC
(SEQ. ID. No. 676) J LA1 15 hm-miR-384_rfam7.0
/5AmMC6/TATGAACAATTTCTAGGAAT (SEQ. ID. No. 677) J LA1 16
hm-miR-425_rfam7.0 /5AmMC6/GGCGGACACGACATTCCCGAT (SEQ. ID. No. 678)
J LA1 17 hm-miR-452rfam7.0 /5AmMC6/GTCTCAGTTTCCTCTGCAAACA (SEQ. ID.
No. 679) J LA1 18 hm-miR-30e-3p_rfam7.0
/5AmMC6/GCTGTAAACATCCGACTGAAAG (SEQ. ID. No. 680) J LA1 04 mr-miR-1
29-3p_rfam7.0 /5AmMC6/ATGCTTTTTGGGGTAAGGGCTT (SEQ. ID. No. 681) J
LA98 mr-mi R-429_rfam7.0 /5AmMC6/ACGGCATTACCAGACAGTATTA (SEQ. ID.
No. 682) J LA1 01 mr-miR-330_rfam7.0
/5AmMC6/TCTCTGCAGGCCCTGTGCTTTGC (SEQ. ID. No. 683) J LA1 02
mr-miR-322_rfam7.0 /5AmMC6/TGTTGCAGCGCTTCATGTTT (SEQ. ID. No. 684)
J LA1 14 m-miR-383_rfam7.0 /5AmMC6/AGCCACAGTCACCTTCTGATCT (SEQ. ID.
No. 685) J LA5 hmr-mi R-451 /5AmMC6/AAACTCAGTAATGGTAACGGTTT (SEQ.
ID. No. 686) J LA20 1 r-miR-421_rfam7.0
/5AmMC6/CAACAAACATTTAATGAGGCC (SEQ. ID. No. 687) J LA202 m-mi
R-463_rfam7.0 /5AmMC6/TGATGGACAACAAATTAGGTA (SEQ. ID. No. 688) J
LA203 m-miR-464_rfam7.0 /5AmMC6/TATCTCACAGAATAAACTTGGTA (SEQ. ID.
No. 689) J LA204 m-miR-465_rfam7.0 /5AmMC6/TCACATCAGTGCCATTCTAAATA
(SEQ. ID. No. 690) J LA205 m-miR-466_rfam7.0
/5AmMC6/GTCTTATGTGTGCGTGTATGTAT (SEQ. ID. No. 691) J LA206
m-miR-467_rfam7.0 /5AmMC6/GTGTAGGTGTGTGTATGTATAT (SEQ. ID. No. 692)
J LA207 m-miR-468_rfam7.0 /5AmMC6/CAGACACACGCACATCAGTCATA (SEQ. ID.
No. 693) J LA208 m-miR-469_rfam7.0
/5AmMC6/GGACACCAAGATCAATGAAAGAGGCA (SEQ. ID. No. 694) J LA209
m-miR-470_rfam7.0 /5AmMC6/TCACCAGTGCCAGTCCAAGAA (SEQ. ID. No. 695)
J LA21 0 m-miR-471_rfam7.0 /5AmMC6/TGTGAAAAGCACTATACTACGTA (SEQ.
ID. No. 696) EAM325 hmr-miR-27a_rfam7.0
/5AmMC6/GGCGGAACTTAGCCACTGTGAA (SEQ. ID. No. 697) EAM326
hmr-miR-296_rfam7.0 /5AmMC6/ACAGGATTGAGGGGGGGCCCT (SEQ. ID. No.
698) EAM327 hmr-miR-299-5p_rfam7.0 /5AmMC6/ATGTATGTGGGACGGTAAACCA
(SEQ. ID. No. 699) EAM328 hmr-miR-301_rfam7.0
/5AmMC6/GCTTTGACAATACTATTGCACTG (SEQ. ID. No. 700) EAM329
hm-miR-302a_rfam7.0 /5AmMC6/TCACCAAACATGGAAGCACTTA (SEQ. ID. No.
701) EAM330 hmr-miR-30a-5p_rfam7.0 /5AmMC6/GCTTCCAGTCGAGGATGTTTACA
(SEQ. ID. No. 702) EAM331 hmr-miR-30e-5p_rfam7.0
/5AmMC6/TCCAGTCAAGGATGTTTACA (SEQ. ID. No. 703) EAM332
hmr-miR-31_rfam7.0 /5AmMC6/CAGCTATGCCAGCATCTTGCCT (SEQ. ID. No.
704) EAM333 hmr-miR-32 rfam7.0 /5AmMC6/GCAACTTAGTAATGTGCAATA (SEQ.
ID. No. 705) EAM335 h-miR-34b_rfam7.0
/5AmMC6/CAATCAGCTAATGACACTGCCT (SEQ. ID. No. 706) EAM336
hmr-miR-34c_rfam7.0 /5AmMC6/GCAATCAGCTAACTACACTGCCT (SEQ. ID. No.
707) EAM337 hmr-miR-93_rfam7.0 /5AmMC6/CTACCTGCACGAACAGCACTTTG
(SEQ. ID. No. 708) EAM208 hmr-miR-1 41_rfam7.0
/5AmMC6/CCATCTTTACCAGACAGTGTT (SEQ. ID. No. 709) EAM207 hmr-miR-1
40 rfam7.0 /5AmMC6/CTACCATAGGGTAAAACCACT (SEQ. ID. No. 710) J LA222
hmr-miR-1 39_rfam7.0 /5AmMC6/TGGAGACACGTGCACTGTAGA (SEQ. ID. No.
711) J LA220 hmr-miR-1 38_rfam7.0 /5AmMC6/CCTGATTCACAACACCAGCTG
(SEQ. ID. No. 712) EAM203 hmr-miR-1 35a_rfam7.0
/5AmMC6/TTCACATAGGAATAAAAAGCCATA (SEQ. ID. No. 713) EAM200
hmr-miR-1 33a_rfam7.0 /5AmMC6/ACAGCTGGTTGAAGGGGACCAA (SEQ. ID. No.
714) EAM 195 hmr-miR-1 28b_rfam7.0 /5AmMC6/GAAAGAGACCGGTTCACTGTGA
(SEQ. ID. No. 715) EAM 194 hmr-miR-1 28a_rfam7.0
/5AmMC6/AAAAGAGACCGGTTCACTGTGA (SEQ. ID. No. 716) EAM254 hmr-miR-21
9_rfam7.0 /5AmMC6/AGAATTGCGTTTGGACAATCA (SEQ. ID. No. 717) EAM257
hmr-miR-221_rfam7.0 /5AmMC6/GAAACCCAGCAGACAATGTAGCT (SEQ. ID.
No.
718) EAM258 hmr-miR-222_rfam7.0 /5AmMC6/GAGACCCAGTAGCCAGATGTAGCT
(SEQ. ID. No. 719) EAM259 hmr-miR-223_rfam7.0
/5AmMC6/GGGGTATTTGACAAACTGACA (SEQ. ID. No. 720) J LA21 1 m-mi
R-434-5p_rfam7.0 /5AmMC6/GGTTCAAACCATGAGTCGAGCT (SEQ. ID. No. 721)
J LA21 2 m-miR-434-3p_rfam7.0 /5AmMC6/GGAGTCGAGTGATGGTTCAAA (SEQ.
ID. No. 722) J LA21 3 m-mi R-433-5p_rfam7.0
/5AmMC6/GAATAATGACAGGCTCACCGTA (SEQ. ID. No. 723) J LA2 hsa-miR-522
/5AmMC6/ACACTCTAAAGGGAACCATTTT (SEQ. ID. No. 724) J LA3 hsa-miR-495
/5AmMC6/AAAGAAGTGCACCATGTTTGTTT (SEQ. ID. No. 725) J LA200
r-miR-297_rfam7.0 /5AmMC6/CATGCATACATGCACACATACAT (SEQ. ID. No.
726) J LA6 hsa-miR-51 8e /5AmMC6/AACACTCTGAAGGGAAGCGC (SEQ. ID. No.
727) J LA7 hsa-miR-5 1 9a /5AmMC6/CACTCTAAAAGGATGCACTTT (SEQ. ID.
No. 728) J LA8 hsa-mir-527* /5AmMC6/TTCACCAAAGGGAAGCACTTT (SEQ. ID.
No. 729) J LA72 hmr-miR-1 40*_rfam7.0 /5AmMC6/GTCCGTGGTTCTACCCTGTGG
(SEQ. ID. No. 730) J LA1 0 hsa-miR-521
/5AmMC6/ACACTCTAAAGGGAAGTGCGTT (SEQ. ID. No. 731) J LA1 2
hsa-miR-362 /5AmMC6/CTCACACCTAGGTTCCAAGGATT (SEQ. ID. No. 732) J
LA74 hsa-mir-1 8* /5AmMC6/CCAGAAGGAGCACTTAGGGCAG (SEQ. ID. No. 733)
J LA1 4 hm-miR-363 /5AmMC6/TTACAGATGGATACCGTGCAATT (SEQ. ID. No.
734) J LA77 hsa-mir-1 9b-1* /5AmMC6/GCTGGATGCAAACCTGCAAAAC (SEQ.
ID. No. 735) J LA1 7 hsa-mir-520c, b, f
/5AmMC6/CCTCTAAAAGGAAGCACTTTCT (SEQ. ID. No. 736) J LA79
hsa-mir-23a* /5AmMC6/AATCCCATCCCCAGGAACCC (SEQ. ID. No. 737) J LA20
hsa-miR-369-5p /5AmMC6/CGAATATAACACGGTCGATCT (SEQ. ID. No. 738) J
LA81 hsa-mir-339* /5AmMC6/CGGCTCTGTCGTCGAGGCGC (SEQ. ID. No. 739) J
LA23 hsa-mir-342* /5AmMC6/TCAATCACAGATAGCACCCCT (SEQ. ID. No. 740)
J LA24 hsa-mir-1 9a* /5AmMC6/GTAGTGCAACTATGCAAAACT (SEQ. ID. No.
741) J LA26 hsa-miR-51 7a, b /5AmMC6/ACACTCTAAAGGGATGCACGAT (SEQ.
ID. No. 742) J LA27 hsa-miR-51 6-5p /5AmMC6/AAAGTGCTTCTTACCTCCAGAT
(SEQ. ID. No. 743) J LA28 hsa-miR-51 8b
/5AmMC6/ACCTCTAAAGGGGAGCGCTT (SEQ. ID. No. 744) J LA29 hsa-miR-51
9d /5AmMC6/ACACTCTAAAGGGAGGCACTTT (SEQ. ID. No. 745) J LA73
hr-mir-1 51* /5AmMC6/ATACTAGACTGTGAGCTCCTCGA (SEQ. ID. No. 746) J
LA31 hsa-mir-28* /5AmMC6/TCCAGGAGCTCACAATCTAGTG (SEQ. ID. No. 747)
JLA33 hsa-mir-51 9a-2* /5AmMC6/AGAAAGCGCTTCCCTGTAGAG (SEQ. ID. No.
748) J LA34 hsa-mir-26b* /5AmMC6/AGCCAAGTAATGGAGAACAGG (SEQ. ID.
No. 749) J LA35 hsa-mir-526c /5AmMC6/AGAAAGCGCTTCCCTCTAGAG (SEQ.
ID. No. 750) J LA36 hsa-miR-527 /5AmMC6/ACAGAAAGGGCTTCCCTTTGC (SEQ.
ID. No. 751) J LA38 hsa-mir-29b-2* /5AmMC6/TCTAAGCCACGATGTGAAACCA
(SEQ. ID. No. 752) J LA39 hsa-let-7g* /5AmMC6/GCAAGGCAGTGGCCTGTACA
(SEQ. ID. No. 753) J LA40 hsa-miR-51 8a
/5AmMC6/TCCAGCAAAGGGAAGCGCTT (SEQ. ID. No. 754) J LA41 hsa-miR-523
/5AmMC6/ACCCTCTATAGGGAAGCGCGT (SEQ. ID. No. 755) JLA44 hsa-miR-51
5-3p /5AmMC6/AACGCTCCAAAAGAAGGCACT (SEQ. ID. No. 756) J LA45
hsa-mir-1 46b* /5AmMC6/ACCAGAACTGAGTCCACAGGG (SEQ. ID. No. 757) J
LA49 hsa-mir-222* /5AmMC6/ATCTACACTGGCTACTGAGCC (SEQ. ID. No. 758)
J LA53 hsa-mir-24* /5AmMC6/ACTGTGTTTCAGCTCAGTAGGCA (SEQ. ID. No.
759) J LA55 hsa-miR-503 /5AmMC6/ACTGCAGAACTGTTCCCGCTG (SEQ. ID. No.
760) J LA57 hsa-mir-505 /5AmMC6/AGAGGAAACCAGCAAGTGTTGA (SEQ. ID.
No. 761) J LA82 hsa-mir-423* /5AmMC6/AAAGTCTCGCTCTCTGCCCCT (SEQ.
ID. No. 762) J LA66 hsa-miR-432 /5AmMC6/CCACCCAATGACCTACTCCAAG
(SEQ. ID. No. 763) J LA83 hsa-mir-425*
/5AmMC6/TCAACGGGAGTGATCGTGTCAT (SEQ. ID. No. 764) JLA84
hsa-mir-92-1* /5AmMC6/AGCATTGCAACCGATCCCAAC (SEQ. ID. No. 765)
JLA69 hsa-mir-1 93* /5AmMC6/TCATCTCGCCCGCAAAGACC (SEQ. ID. No. 766)
J LA70 hsa-miR-51 5-5p /5AmMC6/AGAAAGTGCTTTCTTTTGGAGAA (SEQ. ID.
No. 767) J LA71 hsa-mir-51 6-1* /5AmMC6/GAAAGTGCTTCTTTCCTCGAGAA
(SEQ. ID. No. 768) J LA85 hsa-mir-30d*
/5AmMC6/GCAGCAAACATCTGACTGAAAG (SEQ. ID. No. 769) J LA1 25
h-miR-20b_rfam7.0 /5AmMC6/CTACCTGCACTATGAGCACTTTG (SEQ. ID. No.
770) JLA1 98 h-miR-1 91*_rfam7.0 /5AmMC6/GGGGACGAAATCGAAGCGCAGC
(SEQ. ID. No. 771) J LA1 99 h-miR-1 54*_rfam7.0
/5AmMC6/AATAGGTCAACCGTGTATGATT (SEQ. ID. No. 772) EAM31 6 h-miR-1
47_rfam7.0 /5AmMC6/GCAGAAGCATTTCCACACAC (SEQ. ID. No. 773) EAM31 7
h-miR-1 55_rfam7.0 /5AmMC6/CCCCTATCACGATTAGCATTAA (SEQ. ID. No.
774) EAM31 8 h-miR-1 7-3prfam7.0 /5AmMC6/ACAAGTGCCTTCACTGCAGT (SEQ.
ID. No. 775) J LA1 95 h-miR-200a*_rfam7.0
/5AmMC6/TCCAGCACTGTCCGGTAAGATG (SEQ. ID. No. 776) J LA1 96
h-miR-302a*_rfam7.0 /5AmMC6/AAAGCAAGTACATCCACGTTTA (SEQ. ID. No.
777) J LA1 97 h-miR-299-3p_rfam7.0 /5AmMC6/AAGCGGTTTACCATCCCACATA
(SEQ. ID. No. 778) EAM31 9 h-miR-1 82* rfam7.0
/5AmMC6/TAGTTGGCAAGTCTAGAACCA (SEQ. ID. No. 779) EAM405
h-miR-302b_rfam7.0 /5AmMC6/CTACTAAAACATGGAAGCACTTA (SEQ. ID. No.
780) EAM406 h.about.miR.about.302b*_rfam7.0
/5AmMC6/AGAAAGCACTTCCATGTTAAAGT (SEQ. ID. No. 781) EAM392
r-miR-352_rfam7.0 /5AmMC6/TACTATGCAACCTACTACTCT (SEQ. ID. No. 782)
J LA1 23 h-miR-423_rfam7.0 /5AmMC6/CTGAGGGGCCTCAGACCGAGCT (SEQ. ID.
No. 783) J LA1 24 h-miR-1 8b_rfam7.0 /5AmMC6/TAACTGCACTAGATGCACCTTA
(SEQ. ID. No. 784)
TABLE-US-00010 TABLE 6 Normalized miRNA expression profiling data
for MEP, ERY and MEGA samples Probe ID Description MEP_1 MEP_2
MEP_3 MEP_4 MEP_5 MEP_6 MEP_7 MEP_8 ERY1_1 EAM190 h-miR-10b 6.00
6.78 6.00 6.00 6.44 6.00 6.06 6.00 6.00 EAM187 hmr-miR-107 7.17
6.00 6.65 6.88 6.00 7.44 6.00 6.97 6.85 EAM185 hmr-miR-103 7.59
6.00 7.28 7.38 6.00 7.94 6.00 7.60 7.26 EAM181 hmr-let-7f 9.18 9.82
10.08 10.11 9.68 9.80 9.61 8.96 9.40 EAM179 hmr-let-7d 7.47 9.56
8.99 9.45 8.89 9.76 9.10 9.03 8.76 EAM177 mr-miR-101b 6.00 6.00
6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM175 hmr-miR-320 9.41 8.52
8.86 9.14 9.42 9.49 9.67 9.85 9.17 EAM168 hmr-let-7e 6.00 6.39 6.35
6.00 6.00 6.00 6.00 6.00 6.19 EAM161 hmr-miR-28 6.00 6.00 6.00 6.00
6.00 6.00 7.60 6.00 6.00 EAM160 hmr-miR-26b 8.92 8.03 9.08 9.13
8.76 8.24 8.82 7.56 8.36 EAM155 hmr-miR-136 6.00 6.00 6.00 6.00
6.00 6.00 6.00 6.00 6.00 EAM283 mr-miR-211 6.00 6.00 6.00 6.00 6.00
6.00 6.00 6.00 6.00 EAM282 m-miR-199b 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 6.00 EAM281 mr-miR-217 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 EAM280 hmr-miR-30a- 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 3p EAM279 hmr-miR-29c 6.00 6.98 6.00 6.00 6.00 6.00 6.00
6.00 6.00 EAM278 hmr-miR-98 6.00 7.19 7.59 6.00 7.17 6.00 6.00 6.00
6.74 EAM270 hmr-miR-30b 7.89 7.61 8.70 9.14 8.89 9.10 9.01 9.49
8.81 EAM159 hmr-miR-130a 7.76 8.35 8.79 8.49 8.39 8.29 8.96 9.53
8.41 EAM163 hmr-miR-142- 6.00 6.00 6.00 6.42 6.00 7.29 6.77 6.00
6.39 3p EAM171 hmr-miR-137 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM306 m-miR-201 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM307 m-miR-202 6.00 6.00 6.00 6.00 6.42 6.00 6.00 6.00 6.00
EAM308 hmr-miR-206 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM309 m-miR-207 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM310 hmr-miR-208 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM247 hmr-miR-212 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM251 hmr-miR-216 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM253 hmr-miR-218 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM275 hmr-miR-34a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM246 h-miR-211 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM250 h-miR-215 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM252 h-miR-217 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM224 hmr-miR-17-5p 11.37 11.51 11.39 10.79 11.11 11.33 11.35
11.44 11.52 EAM225 hmr-miR-18a 6.00 6.00 6.00 7.67 6.07 6.00 6.00
8.32 8.14 EAM226 hmr-miR-181a 6.26 8.16 7.40 8.99 9.49 8.48 8.90
7.90 8.54 EAM227 hmr-miR-181b 6.00 6.00 8.18 8.18 6.59 7.95 7.59
9.07 7.76 EAM234 hmr-miR-199a 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 EAM235 h-miR-199b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM236 hmr-miR-19a 7.89 7.04 8.46 8.23 8.32 7.24 7.94 7.49
8.65 EAM241 hmr-miR-203 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM242 hmr-miR-204 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM243 hmr-miR-205 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM245 hmr-miR-210 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM249 hmr-miR-214 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM184 hmr-miR-100 6.00 6.00 6.26 6.00 6.00 6.00 6.00 6.00
6.00 EAM186 h-miR-106a 11.10 11.31 11.28 10.79 10.90 11.00 11.02
11.32 11.22 EAM189 hmr-miR-10a 8.48 7.98 7.43 7.74 7.44 6.44 7.37
6.00 7.48 EAM191 hmr-miR-122a 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 EAM192 hmr-miR-126* 7.32 6.00 7.66 6.20 6.62 6.00 6.76
7.63 7.39 EAM198 hmr-miR-130b 6.00 6.00 6.36 6.44 6.68 6.00 6.00
6.68 6.00 EAM202 hmr-miR-134 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 EAM209 hmr-miR-142- 6.00 7.72 7.42 6.95 8.16 6.62 7.29
7.92 6.00 5p EAM221 m-miR-155 7.57 8.58 7.87 7.76 7.43 7.79 7.65
7.47 7.97 EAM223 hmr-miR-15b 10.67 8.82 10.83 10.79 10.29 10.53
10.47 9.94 10.59 EAM228 hmr-miR-181c 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 6.00 EAM222 hm-miR-15a 8.94 6.00 8.11 9.87 8.82 8.92 8.20
8.39 8.30 EAM111 hm-let-7g 10.22 9.62 10.09 10.09 9.76 10.06 9.73
9.61 9.34 EAM131 hmr-miR-92 11.06 11.53 11.55 10.98 11.69 11.74
11.75 11.88 11.30 EAM139 hmr-miR-146a 9.03 9.70 6.00 9.07 9.31 6.00
8.53 9.49 9.22 EAM145 hmr-let-7c 9.28 9.27 9.03 9.67 9.39 9.04 9.24
9.14 8.71 EAM109 hmr-miR-7 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM152 hm-miR-9* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA215 hmr-let-7i 9.03 8.00 8.07 8.44 7.26 8.38 8.85 7.71 9.25
EAM153 hmr-let-7a 11.22 10.91 10.80 10.07 11.01 10.77 11.09 10.93
10.63 EAM147 hmr-let-7b 9.07 6.31 9.13 8.64 9.00 9.63 10.04 9.43
7.66 EAM137 hmr-miR-132 6.00 6.00 6.00 6.00 6.34 6.00 6.00 6.00
6.00 EAM133 hmr-miR-324- 7.74 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 5p EAM103 hmr-miR-124a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM105 hmr-miR-125b 6.00 7.69 7.56 8.05 8.75 8.32 6.81 7.30
8.45 EAM121 hmr-miR-99a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM115 hmr-miR-16 12.32 12.42 12.31 11.40 11.87 12.30 11.83
11.81 12.08 EAM119 hmr-miR-29b 6.00 6.00 6.00 6.93 6.00 6.00 6.00
6.00 6.00 EAM311 hmr-miR-101 6.00 6.00 6.00 6.00 6.00 6.00 6.39
6.00 6.00 EAM312 h-miR-105 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM313 hmr-miR-106b 9.31 9.44 8.80 9.39 9.18 9.09 8.34 8.86
8.75 EAM314 hmr-miR-126 8.75 9.89 8.72 10.12 9.41 8.10 9.63 8.69
10.57 EAM315 hmr-miR-127 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM320 hm-miR-189 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA216 hmr-miR-200c 6.00 6.00 6.00 6.00 6.00 6.00 8.00 6.00 7.19
EAM323 h-miR-224 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM324 hmr-miR-25 6.00 9.01 6.41 7.40 8.30 7.82 8.26 8.59 7.82
EAM386 r-miR-336 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA218 r-miR-343 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM388 r-miR-344 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM338 h-miR-95 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA214
hmr-miR-129 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM340
mr-let-7d* 7.71 6.00 6.00 6.00 6.00 7.41 6.00 6.00 6.00 EAM341
m-miR-106a 10.34 11.12 10.40 9.97 10.46 10.70 10.47 10.68 10.60
EAM342 hmr-miR-135b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM343 mr-miR-151 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM344 m-miR-17-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM345 m-miR-224 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM346 mr-miR-290 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM347 mr-miR-291-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM348 mr-miR-291-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM349 mr-miR-292-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM350 mr-miR-292-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM351 m-miR-293 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM352 m-miR-294 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM353 m-miR-295 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM354 m-miR-297 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM355 mr-miR-298 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM356 mr-miR-300 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM358 hmr-miR-323 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM359 hmr-miR-324-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 7.59 6.00
EAM360 mr-miR-325 7.36 6.93 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM361 hmr-miR-326 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM362 hmr-miR-328 6.00 6.00 6.98 6.00 6.00 6.00 6.00 6.00 6.00
EAM363 mr-miR-329 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM365 hmr-miR-331 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM366 mr-miR-337 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM367 hmr-miR-338 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM368 hmr-miR-339 6.00 6.00 6.00 6.00 6.10 6.00 6.00 6.00 6.00
EAM369 hmr-miR-340 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM370 mr-miR-341 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM371 hmr-miR-342 9.66 9.70 6.00 10.47 9.48 9.58 10.06 9.41 8.70
EAM372 m-miR-344 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM373 mr-miR-345 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM374 m-miR-346 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM375 mr-miR-34b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA217 mr-miR-350 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM377 mr-miR-351 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM378 mr-miR-7b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM382 r-miR-20* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM383 r-miR-327 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM384 r-miR-333 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM385 hmr-miR-335 6.91 7.60 8.50 7.99 7.28 6.00 7.20 7.07 7.65
EAM393 r-miR-7* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM304
hmr-miR-200a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM298
hmr-miR-194 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA221
hmr-miR-191 7.79 6.44 7.74 8.72 8.73 8.28 8.34 8.43 7.85 EAM295
hmr-miR-190 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM292
hmr-miR-186 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA219
hmr-miR-185 6.00 6.00 6.00 6.07 7.36 7.59 6.40 6.00 6.00 EAM290
hmr-miR-184 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM402
hm-miR-133b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM403
h-miR-151 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM404
hmr-miR-196b 6.00 6.00 6.00 6.52 6.00 6.00 6.00 6.00 6.00 EAM418
hm-miR-370 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM419
h-miR-371 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM420
h-miR-372 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM421
h-miR-373 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM422
h-miR-373* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM423
h-miR-374 6.00 6.69 6.19 7.70 7.86 6.00 6.69 6.60 7.31 EAM426
m-miR-215 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM427
hm-miR-409-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM428
hm-miR-410 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM429
m-miR-376b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM430
m-miR-376a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM431
m-miR-411 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM432
m-miR-380-3p 6.00 6.00 6.00 6.00 6.60 6.00 6.00 6.00 6.00 EAM433
hm-miR-412 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM264
hmr-miR-27b 7.18 6.00 6.78 7.56 8.20 6.00 6.00 6.80 7.55 EAM263
hmr-miR-26a 9.87 9.50 10.10 9.97 9.68 9.23 9.40 10.04 10.07 EAM262
hmr-miR-24 6.00 6.25 6.00 6.94 6.00 6.00 6.00 6.00 7.29 EAM261
hmr-miR-23b 7.42 7.66 7.78 8.90 8.11 7.19 9.17 8.50 7.90 EAM260
hmr-miR-23a 7.78 8.15 7.85 9.30 7.94 8.13 8.87 8.83 8.09 EAM256
h-miR-220 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM255
hmr-miR-22 6.00 6.24 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM248
hmr-miR-213 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM244
hmr-miR-21 6.39 7.99 8.45 8.89 8.32 9.27 8.02 7.77 7.86 EAM240
hmr-miR-20a 11.36 11.38 11.87 11.08 11.27 11.19 11.27 11.27 11.50
EAM237 hmr-miR-19b 8.88 7.38 9.64 9.13 8.68 8.34 8.68 8.09 9.38
EAM233 hmr-miR-196a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM214 hm-miR-148a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM212 hmr-miR-145 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM211 hmr-miR-144 9.13 7.29 6.00 6.37 6.88 7.86 6.00 6.00 6.00
EAM210 hmr-miR-143 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM389 r-miR-346 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM390 r-miR-347 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM391 r-miR-349 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA223 hmr-miR-33 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM277 hmr-miR-96 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM276 hmr-miR-9 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM272 hmr-miR-30d 7.05 6.00 7.40 8.82 8.29 8.37 8.23 8.50 8.82
EAM288 mr-miR-10b 6.74 8.16 6.94 6.48 7.41 6.00 6.56 6.00 6.00
EAM293 hm-miR-188 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM297 hmr-miR-193a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM301 h-miR-198 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM232 hmr-miR-192 6.11 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM231 hmr-miR-187 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM230 hmr-miR-183 6.00 6.00 6.00 6.00 6.29 6.00 6.00 6.00 6.00
EAM229 hm-miR-182 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM220 hmr-miR-154 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM219 hmr-miR-153 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM218 hmr-miR-152 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM217 hmr-miR-150 6.00 7.22 6.00 6.00 6.00 7.52 6.00 6.00 6.78
EAM216 hm-miR-149 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM215 hmr-miR-148b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM271 hmr-miR-30c 7.66 7.76 8.70 9.30 9.01 9.25 9.17 9.58 8.66
EAM268 hmr-miR-29a 6.19 7.88 6.00 6.00 6.00 6.68 6.00 6.00 6.90
EAM305 hmr-miR-200b 6.00 6.00 6.00 6.00 6.28 6.00 7.02 6.00 6.46
EAM303 hm-miR-199a* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM300 h-miR-197 7.59 6.00 6.82 7.62 8.19 7.13 6.99 8.12 8.11
EAM299 hmr-miR-195 9.34 9.94 9.20 8.70 8.93 9.57 8.49 8.73 9.15
JLA91 hmr-miR-99b 9.43 8.63 6.00 9.99 7.89 8.23 7.06 7.31 6.00
JLA92 hmr-miR-433 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA93 hmr-miR-431 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA94 hmr-miR-365 8.38 6.00 8.96 7.30 7.15 6.00 6.43 6.00 6.00
JLA95 hmr-miR-450 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA96 hmr-miR-449 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA99 hmr-miR-448 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA103 hmr-miR-424 6.00 6.20 6.81 7.28 6.00 6.00 6.66 6.00 7.64
JLA105 hm-miR-361 6.00 6.01 6.00 7.74 7.07 7.28 7.99 6.00 7.46
JLA106 hm-miR-375 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA107 hm-miR-377 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA108 hm-miR-378 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA109 hm-miR-379 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA110 hm-miR-380-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA111 hm-miR-381 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA112 hm-miR-382 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA115 hm-miR-384 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA116 hm-miR-425 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA117 hm-miR-452 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA118 hm-miR-30e-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA104 mr-miR-129-3p 9.27 6.00 9.25 6.00 8.52 6.00 7.63 7.12 6.00
JLA98 mr-miR-429 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA101 mr-miR-330 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA102 mr-miR-322 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA114 m-miR-383 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA5
hmr-miR-451 9.95 8.32 6.00 6.85 9.54 8.59 6.00 6.33 6.00 JLA201
r-miR-421 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA202
m-miR-463 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA203
m-miR-464 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA204
m-miR-465 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA205
m-miR-466 7.94 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA206
m-miR-467 8.36 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA207
m-miR-468 6.05 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA208
m-miR-469 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA209
m-miR-470 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA210
m-miR-471 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM325
hmr-miR-27a 8.16 6.00 7.67 8.75 8.56 6.00 6.00 7.93 8.44 EAM326
hmr-miR-296 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM327
hmr-miR-299-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM328
hmr-miR-301 6.25 6.00 6.00 6.00 6.00 6.00 6.00 6.56 6.16 EAM329
hm-miR-302a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM330 hmr-miR-30a-5p 6.00 6.01 6.00 7.29 6.25 6.55 6.00 6.78 7.23
EAM331 hmr-miR-30e-5p 6.00 6.21 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM332 hmr-miR-31 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM333 hmr-miR-32 7.38 6.00 6.21 6.00 6.00 6.00 6.00 6.00 6.00
EAM335 h-miR-34b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM336 hmr-miR-34c 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM337 hmr-miR-93 8.93 9.74 9.14 9.92 8.36 10.06 10.35 9.58 10.28
EAM208 hmr-miR-141 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM207 hmr-miR-140 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA222 hmr-miR-139 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA220 hmr-miR-138 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM203 hmr-miR-135a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM200 hmr-miR-133a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM hmr-miR-128b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM
hmr-miR-128a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM254
hmr-miR-219 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM257
hmr-miR-221 7.93 6.55 6.23 6.00 6.00 6.00 6.00 6.00 6.29 EAM258
hmr-miR-222 6.00 8.99 9.28 8.07 8.88 8.98 9.45 8.55 8.72 EAM259
hmr-miR-223 7.82 7.94 7.94 8.62 7.50 8.85 8.28 8.36 8.42 JLA211
m-miR-434-5p 6.65 6.49 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA212
m-miR-434-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA213
m-miR-433-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA2
hsa-miR-522 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA3
hsa-miR-495 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA200
r-miR-297 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA6
hsa-miR-518e 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA7
hsa-miR-519a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA8
hsa-mir-527* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA72
hmr-miR-140* 8.13 6.00 6.00 7.81 7.88 6.14 6.00 6.44 6.00 JLA10
hsa-miR-521 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA12
hsa-miR-362 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA74
hsa-mir-18* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA14
hm-miR-363 6.31 6.77 6.00 7.17 6.26 6.00 6.00 7.78 6.35 JLA77
hsa-mir-19b-1* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA17
hsa-mir- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 520c,b,f
JLA79 hsa-mir-23a* 6.00 7.27 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA20 hsa-miR-369-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA81 hsa-mir-339* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA23 hsa-mir-342* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.10 6.00
JLA24 hsa-mir-19a* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA26 hsa-miR-517a,b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 7.45
JLA27 hsa-miR-516-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.26
JLA28 hsa-miR-518b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA29 hsa-miR-519d 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.43
JLA73 hr-mir-151* 7.12 6.00 6.00 6.00 7.45 7.00 7.48 6.00 6.35
JLA31 hsa-mir-28* 6.00 6.00 6.00 6.31 6.00 6.00 6.00 6.00 6.00
JLA33 hsa-mir-519a-2* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA34 hsa-mir-26b* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA35 hsa-miR-526c 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA36 hsa-miR-527 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA38 hsa-mir-29b-2* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA39 hsa-let-7g* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA40 hsa-miR-518a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA41 hsa-miR-523 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA44 hsa-miR-515-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA45 hsa-mir-146b* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA49 hsa-mir-222* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA53 hsa-mir-24* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA55 hsa-miR-503 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA57 hsa-mir-505 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA82 hsa-mir-423* 10.00 10.80 10.94 10.76 10.93 10.75 10.65 10.87
10.46 JLA66 hsa-miR-432 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 JLA83 hsa-mir-425* 6.00 6.00 6.77 7.81 8.68 7.65 7.36 6.86
6.00 JLA84 hsa-mir-92-1* 6.00 6.00 6.00 7.03 6.00 6.00 6.00 6.00
6.00 JLA69 hsa-mir-193* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 JLA70 hsa-miR-515-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 JLA71 hsa-mir-516-1* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 JLA85 hsa-mir-30d* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 JLA125 h-miR-20b 10.18 10.08 10.29 9.65 9.78 10.07 9.95 10.22
10.08 JLA198 h-miR-191* 6.00 6.00 6.00 6.00 6.00 6.36 6.00 6.00
6.00 JLA199 h-miR-154* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM316 h-miR-147 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM317 h-miR-155 9.59 10.47 9.67 10.45 9.61 9.58 9.48 9.42 9.75
EAM318 h-miR-17-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 7.19 6.00
JLA195 h-miR-200a* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA196 h-miR-302a* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA197 h-miR-299-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 7.25
EAM319 h-miR-182* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM405 h-miR-302b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM406 h-miR-302b* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM392 r-miR-352 6.25 7.91 7.30 8.16 7.22 8.24 7.61 7.55 7.24
JLA123 h-miR-423 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA124 h-miR-18b 6.00 6.00 6.00 7.59 6.00 6.00 6.00 8.06 8.14
ProbeID Description ERY1_2 ERY1_3 ERY1_4 ERY2_1 ERY2_2 ERY2_3
ERY3_1 ERY3_2 MEGA1_1 EAM190 h-miR-10b 6.00 6.99 6.75 6.00 6.00
7.96 6.06 6.00 6.00 EAM187 hmr-miR-107 8.25 6.00 7.84 6.00 7.81
6.90 6.00 7.49 8.75 EAM185 hmr-miR-103 8.79 6.00 8.39 6.00 8.34
7.93 6.00 7.79 9.02 EAM181 hmr-let-7f 7.95 8.58 8.86 9.12 9.72 6.00
9.09 8.47 9.80 EAM179 hmr-let-7d 7.02 7.49 8.73 7.65 9.88 8.43 9.02
9.01 9.57 EAM177 mr-miR-101b 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 EAM175 hmr-miR-320 9.89 9.23 8.71 8.40 10.08 7.51 6.66
7.03 8.58 EAM168 hmr-let-7e 6.00 6.93 6.00 6.00 6.62 6.00 6.00 6.00
6.00 EAM161 hmr-miR-28 6.00 6.00 6.00 6.00 6.08 6.00 6.00 6.00 7.52
EAM160 hmr-miR-26b 8.10 8.96 9.69 9.37 9.42 7.41 8.32 7.48 9.69
EAM155 hmr-miR-136 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM283 mr-miR-211 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM282 m-miR-199b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM281 mr-miR-217 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM280 hmr-miR-30a- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 3p
EAM279 hmr-miR-29c 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM278 hmr-miR-98 6.00 6.00 6.00 6.25 6.00 6.00 6.00 6.00 6.00
EAM270 hmr-miR-30b 8.99 7.63 8.95 8.53 9.45 7.95 7.36 6.00 9.58
EAM159 hmr-miR-130a 8.43 8.44 7.06 6.00 8.49 9.20 6.00 6.00 9.15
EAM163 hmr-miR-142- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 7.47 3p
EAM171 hmr-miR-137 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM306 m-miR-201 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM307 m-miR-202 6.00 6.00 6.00 6.00 6.00 7.33 6.67 6.00 6.00
EAM308 hmr-miR-206 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM309 m-miR-207 6.00 6.00 6.00 7.37 6.00 6.00 6.00 6.00 6.00
EAM310 hmr-miR-208 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM247 hmr-miR-212 6.00 6.37 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM251 hmr-miR-216 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM253 hmr-miR-218 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM275 hmr-miR-34a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM246 h-miR-211 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM250 h-miR-215 6.00 6.00 6.92 6.00 6.00 6.00 6.40 7.44 6.00
EAM252 h-miR-217 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM224 hmr-miR-17-5p 11.52 10.93 10.34 10.89 10.35 11.50 10.47
10.31 10.24 EAM225 hmr-miR-18a 7.13 7.50 6.00 6.00 6.00 7.18 6.00
6.00 6.00 EAM226 hmr-miR-181a 7.91 9.01 7.64 6.00 8.20 6.00 6.00
6.00 8.26 EAM227 hmr-miR-181b 6.95 7.06 6.00 6.00 7.97 6.00 6.00
6.00 6.00 EAM234 hmr-miR-199a 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 EAM235 h-miR-199b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM236 hmr-miR-19a 7.76 8.02 7.53 8.50 7.41 7.49 6.00 7.84
7.23 EAM241 hmr-miR-203 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM242 hmr-miR-204 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM243 hmr-miR-205 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.69 EAM245 hmr-miR-210 6.00 6.00 6.48 6.00 6.00 6.00 6.00 6.00
6.00 EAM249 hmr-miR-214 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM184 hmr-miR-100 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM186 h-miR-106a 11.18 10.83 10.11 10.62 10.16 11.33 10.18
10.13 10.04 EAM189 hmr-miR-10a 6.00 7.49 9.10 6.00 6.43 6.00 6.00
6.00 6.54 EAM191 hmr-miR-122a 6.00 6.00 7.20 6.00 6.00 6.00 6.00
6.00 6.00 EAM192 hmr-miR-126* 7.58 8.43 8.67 6.00 6.00 6.00 6.00
6.00 8.11 EAM198 hmr-miR-130b 6.00 6.01 6.00 6.00 7.44 6.00 6.00
7.98 6.00 EAM202 hmr-miR-134 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 EAM209 hmr-miR-142- 8.13 6.00 6.75 6.77 7.48 8.09 6.00
6.00 9.02 5p EAM221 m-miR-155 7.36 7.54 6.00 6.59 7.89 6.00 6.00
6.00 6.00 EAM223 hmr-miR-15b 10.30 9.57 10.03 11.29 10.88 11.16
11.83 11.90 11.05 EAM228 hmr-miR-181c 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 6.00 EAM222 hm-miR-15a 7.27 8.26 6.00 8.36 9.42 10.08
10.72 9.83 8.88 EAM111 hm-let-7g 8.71 9.39 9.63 9.43 10.51 10.13
6.00 9.81 10.39 EAM131 hmr-miR-92 11.87 11.49 9.87 11.68 11.05 9.45
11.53 11.40 8.71 EAM139 hmr-miR-146a 7.16 9.30 8.85 6.00 9.34 10.46
6.82 6.00 10.20 EAM145 hmr-let-7c 8.87 10.13 10.11 9.49 9.50 9.31
8.41 8.87 8.35 EAM109 hmr-miR-7 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 EAM152 hm-miR-9* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 JLA215 hmr-let-7i 6.00 6.35 9.31 7.17 8.40 9.25 6.00 7.09 8.55
EAM153 hmr-let-7a 10.73 11.16 12.01 10.47 10.87 11.26 10.78 11.14
10.70 EAM147 hmr-let-7b 7.57 9.14 8.77 9.57 9.66 6.51 7.43 7.57
8.10 EAM137 hmr-miR-132 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM133 hmr-miR-324- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 5p EAM103 hmr-miR-124a 6.00 6.00 6.00 6.00 6.00 6.21 6.00 6.00
6.00 EAM105 hmr-miR-125b 7.21 7.24 7.48 6.00 6.34 6.00 6.00 6.23
6.00 EAM121 hmr-miR-99a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM115 hmr-miR-16 12.08 12.26 12.61 12.97 12.35 12.37 13.12
12.85 12.67 EAM119 hmr-miR-29b 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 EAM311 hmr-miR-101 6.00 6.24 6.18 6.00 6.00 6.00 6.00
6.00 6.00 EAM312 h-miR-105 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM313 hmr-miR-106b 8.64 8.72 9.09 9.65 7.84 9.00 8.32 8.32
8.32 EAM314 hmr-miR-126 10.18 11.18 11.85 7.84 9.11 6.00 6.00 6.00
7.96 EAM315 hmr-miR-127 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM320 hm-miR-189 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA216 hmr-miR-200c 6.00 6.00 6.00 6.00 7.88 6.00 6.00 6.00 6.00
EAM323 h-miR-224 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.49
EAM324 hmr-miR-25 8.01 8.81 6.04 7.43 8.29 6.00 6.00 8.55 7.79
EAM386 r-miR-336 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA218 r-miR-343 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM388 r-miR-344 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM338 h-miR-95 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA214
hmr-miR-129 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM340
mr-let-7d* 6.00 7.18 6.00 6.00 6.00 6.00 6.00 8.01 6.00 EAM341
m-miR-106a 10.77 10.26 10.07 10.38 9.39 10.73 9.85 9.85 9.54 EAM342
hmr-miR-135b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM343
mr-miR-151 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM344
m-miR-17-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM345
m-miR-224 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM346
mr-miR-290 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM347
mr-miR-291-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM348
mr-miR-291-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM349
mr-miR-292-3p 6.00 6.00 7.71 6.00 6.00 6.00 6.00 6.00 6.00 EAM350
mr-miR-292-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM351
m-miR-293 6.00 6.00 6.00 8.36 6.00 6.45 6.69 6.00 6.00 EAM352
m-miR-294 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM353
m-miR-295 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM354
m-miR-297 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM355
mr-miR-298 6.00 6.00 6.00 6.00 6.00 6.00 10.24 6.00 6.00 EAM356
mr-miR-300 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM358
hmr-miR-323 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM359
hmr-miR-324- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 3p EAM360
mr-miR-325 6.00 6.00 7.44 6.00 6.00 6.39 6.00 6.00 6.00 EAM361
hmr-miR-326 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM362
hmr-miR-328 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM363
mr-miR-329 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM365
hmr-miR-331 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM366
mr-miR-337 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM367
hmr-miR-338 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM368
hmr-miR-339 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM369
hmr-miR-340 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM370
mr-miR-341 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM371
hmr-miR-342 7.83 6.00 6.00 9.42 10.64 9.88 6.00 9.57 10.38 EAM372
m-miR-344 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM373
mr-miR-345 6.00 6.00 6.00 6.00 6.00 6.00 7.09 6.00 6.00 EAM374
m-miR-346 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM375
mr-miR-34b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA217
mr-miR-350 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM377
mr-miR-351 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM378
mr-miR-7b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM382
r-miR-20* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM383
r-miR-327 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM384
r-miR-333 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM385
hmr-miR-335 7.14 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM393
r-miR-7* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM304
hmr-miR-200a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM298
hmr-miR-194 6.07 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.48 JLA221
hmr-miR-191 8.31 6.00 6.60 8.62 7.95 7.15 8.30 8.00 8.50 EAM295
hmr-miR-190 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM292
hmr-miR-186 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA219
hmr-miR-185 6.00 7.21 6.00 6.54 7.12 6.00 7.47 9.59 6.23 EAM290
hmr-miR-184 6.00 6.21 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM402
hm-miR-133b 6.00 6.00 7.29 6.00 6.00 6.00 6.00 6.00 6.00 EAM403
h-miR-151 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM404
hmr-miR-196b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM418
hm-miR-370 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM419
h-miR-371 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM420
h-miR-372 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM421
h-miR-373 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM422
h-miR-373* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM423
h-miR-374 6.00 7.19 7.18 6.25 7.10 6.61 6.00 6.00 6.70 EAM426
m-miR-215 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM427
hm-miR-409- 6.54 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 3p EAM428
hm-miR-410 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM429
m-miR-376b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM430
m-miR-376a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM431
m-miR-411 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM432
m-miR-380-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM433
hm-miR-412 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM264
hmr-miR-27b 6.00 6.00 8.78 6.80 6.95 8.02 6.00 7.45 8.57 EAM263
hmr-miR-26a 9.27 9.43 9.90 9.27 9.26 8.54 8.77 8.20 10.49 EAM262
hmr-miR-24 6.00 6.00 8.39 7.36 6.00 6.00 6.00 6.00 6.00
EAM261 hmr-miR-23b 7.59 8.64 8.06 7.72 8.59 8.34 6.92 7.59 8.07
EAM260 hmr-miR-23a 8.42 9.19 8.03 8.11 8.60 8.55 6.00 6.00 8.15
EAM256 h-miR-220 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM255 hmr-miR-22 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.46
EAM248 hmr-miR-213 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM244 hmr-miR-21 8.34 8.60 6.73 6.00 8.29 7.93 6.00 6.00 9.48
EAM240 hmr-miR-20a 11.40 11.35 9.92 11.02 10.86 12.04 10.43 10.13
10.28 EAM237 hmr-miR-19b 8.65 9.13 8.54 9.35 8.39 8.54 6.00 8.44
7.57 EAM233 hmr-miR-196a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM214 hm-miR-148a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM212 hmr-miR-145 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.40 EAM211 hmr-miR-144 6.00 6.00 6.00 8.80 6.00 8.40 11.13 10.47
7.05 EAM210 hmr-miR-143 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 EAM389 r-miR-346 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM390 r-miR-347 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM391 r-miR-349 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA223 hmr-miR-33 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM277 hmr-miR-96 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM276 hmr-miR-9 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM272 hmr-miR-30d 8.59 6.70 8.78 7.19 8.38 6.00 6.00 6.04 8.35
EAM288 mr-miR-10b 6.00 6.00 7.04 6.00 6.00 7.72 6.00 6.98 6.00
EAM293 hm-miR-188 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM297 hmr-miR-193a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM301 h-miR-198 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM232 hmr-miR-192 6.00 6.00 6.00 6.00 6.00 6.00 7.14 7.65 6.00
EAM231 hmr-miR-187 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM230 hmr-miR-183 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM229 hm-miR-182 6.00 6.00 6.00 6.39 6.00 6.00 6.00 6.00 6.00
EAM220 hmr-miR-154 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM219 hmr-miR-153 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM218 hmr-miR-152 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.74
EAM217 hmr-miR-150 6.00 6.00 8.16 6.79 9.98 6.00 6.00 6.15 10.77
EAM216 hm-miR-149 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM215 hmr-miR-148b 6.00 6.83 6.00 6.00 6.00 6.00 6.00 6.00 7.49
EAM271 hmr-miR-30c 9.13 7.46 8.56 8.72 9.62 7.65 7.67 6.00 9.52
EAM268 hmr-miR-29a 6.00 6.00 6.85 6.00 6.20 6.00 6.00 6.00 6.00
EAM305 hmr-miR-200b 6.00 6.00 6.00 6.00 7.01 6.00 6.00 6.00 6.00
EAM303 hm-miR-199a* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM300 h-miR-197 8.29 8.88 7.83 8.40 8.70 6.00 6.00 6.84 7.76
EAM299 hmr-miR-195 9.77 9.49 9.17 10.48 9.03 9.81 10.31 9.58 9.72
JLA91 hmr-miR-99b 10.42 6.63 8.77 6.00 6.00 6.00 6.00 6.00 6.00
JLA92 hmr-miR-433 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA93 hmr-miR-431 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA94 hmr-miR-365 6.06 7.03 7.03 6.00 6.00 8.39 6.22 6.53 8.13
JLA95 hmr-miR-450 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA96 hmr-miR-449 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA99 hmr-miR-448 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA103 hmr-miR-424 6.00 9.39 9.21 6.98 6.00 6.00 6.00 6.00 6.00
JLA105 hm-miR-361 6.00 8.25 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA106 hm-miR-375 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA107 hm-miR-377 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA108 hm-miR-378 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA109 hm-miR-379 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA110 hm-miR-380- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 5p
JLA111 hm-miR-381 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA112 hm-miR-382 8.83 6.00 6.00 6.00 7.08 6.00 6.00 6.00 6.00
JLA115 hm-miR-384 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA116 hm-miR-425 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA117 hm-miR-452 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA118 hm-miR-30e- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 3p
JLA104 mr-miR-129-3p 7.18 6.00 6.00 6.24 6.00 7.62 8.58 7.16 7.12
JLA98 mr-miR-429 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA101 mr-miR-330 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA102 mr-miR-322 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA114 m-miR-383 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA5
hmr-miR-451 6.00 6.15 7.06 9.77 7.29 6.77 11.41 12.04 6.79 JLA201
r-miR-421 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA202
m-miR-463 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA203
m-miR-464 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA204
m-miR-465 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA205
m-miR-466 6.00 6.00 6.00 6.00 6.00 7.54 6.48 6.00 6.00 JLA206
m-miR-467 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA207
m-miR-468 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA208
m-miR-469 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA209
m-miR-470 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA210
m-miR-471 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM325
hmr-miR-27a 6.00 6.00 8.84 7.51 7.75 9.09 6.00 6.80 9.54 EAM326
hmr-miR-296 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM327
hmr-miR-299- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM328
hmr-miR-301 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM329
hm-miR-302a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM330
hmr-miR-30a- 6.05 6.84 8.16 6.64 6.71 6.00 6.00 6.00 6.62 EAM331
hmr-miR-30e- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM332
hmr-miR-31 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM333
hmr-miR-32 6.00 7.53 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM335
h-miR-34b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM336
hmr-miR-34c 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM337
hmr-miR-93 9.86 7.32 6.00 9.38 9.47 8.20 7.82 10.69 8.89 EAM208
hmr-miR-141 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM207
hmr-miR-140 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA222
hmr-miR-139 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA220
hmr-miR-138 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM203
hmr-miR-135a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM200
hmr-miR-133a 6.00 6.00 7.18 6.00 6.00 6.00 6.00 6.00 6.00 EAM
hmr-miR-128b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM
hmr-miR-128a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 EAM254
hmr-miR-219 6.00 6.00 6.00 6.00 6.00 6.00 6.45 6.00 6.00 EAM257
hmr-miR-221 6.00 7.88 6.00 6.00 6.00 6.00 8.25 6.00 8.79 EAM258
hmr-miR-222 6.90 7.15 7.46 7.68 8.11 6.00 6.00 6.00 8.38 EAM259
hmr-miR-223 8.26 6.46 6.31 9.11 8.85 8.89 6.00 6.00 8.82 JLA211
m-miR-434-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA212
m-miR-434-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA213
m-miR-433-5p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA2
hsa-miR-522 6.00 6.00 6.86 6.00 6.00 6.00 6.00 6.00 6.00 JLA3
hsa-miR-495 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA200
r-miR-297 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA6
hsa-miR-518e 6.00 6.00 6.00 6.00 6.00 6.00 6.58 6.67 6.00 JLA7
hsa-miR-519a 6.00 6.80 7.83 6.00 6.00 6.00 6.68 6.53 6.00 JLA8
hsa-mir-527* 6.00 6.00 6.00 6.00 6.00 6.00 6.19 6.07 6.00 JLA72
hmr-miR-140* 6.00 6.00 6.01 6.00 8.10 6.00 6.71 7.22 7.30 JLA10
hsa-miR-521 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA12
hsa-miR-362 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA74
hsa-mir-18* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA14
hm-miR-363 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA77
hsa-mir-19b-1* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 JLA17
hsa-mir- 6.00 6.00 6.69 6.00 6.00 6.00 6.00 6.00 6.00 520c,b,f
JLA79 hsa-mir-23a* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA20 hsa-miR-369- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 5p
JLA81 hsa-mir-339* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA23 hsa-mir-342* 7.31 6.00 6.00 6.00 6.00 6.00 6.00 6.00 8.07
JLA24 hsa-mir-19a* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA26 hsa-miR- 9.19 9.68 9.88 6.00 6.00 6.00 6.00 6.00 6.00 517a,b
JLA27 hsa-miR-516- 8.01 7.22 8.30 6.00 6.00 6.00 6.00 6.00 6.00 5p
JLA28 hsa-miR-518b 6.00 6.00 6.10 6.00 6.00 6.00 6.00 6.00 6.00
JLA29 hsa-miR-519d 6.00 8.31 9.35 6.00 6.00 6.00 6.00 6.00 6.00
JLA73 hr-mir-151* 8.47 6.00 6.00 6.00 7.04 6.00 6.03 8.07 7.32
JLA31 hsa-mir-28* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA33 hsa-mir- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 519a-2*
JLA34 hsa-mir-26b* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA35 hsa-miR-526c 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA36 hsa-miR-527 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA38 hsa-mir-29b-2* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA39 hsa-let-7g* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA40 hsa-miR-518a 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA41 hsa-miR-523 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA44 hsa-miR-515- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 3p
JLA45 hsa-mir-146b* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA49 hsa-mir-222* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA53 hsa-mir-24* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA55 hsa-miR-503 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA57 hsa-mir-505 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA82 hsa-mir-423* 10.59 11.08 10.84 10.71 10.99 9.16 12.28 11.26
10.01 JLA66 hsa-miR-432 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 JLA83 hsa-mir-425* 6.69 9.11 6.64 8.35 7.69 6.00 6.09 6.00
8.19 JLA84 hsa-mir-92-1* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 JLA69 hsa-mir-193* 6.00 6.00 6.00 6.00 6.00 6.88 7.72 6.00
6.00 JLA70 hsa-miR-515- 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 5p JLA71 hsa-mir-516-1* 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 JLA85 hsa-mir-30d* 6.00 6.00 6.00 6.00 6.00 6.00 6.00
6.00 6.00 JLA125 h-miR-20b 10.33 10.27 8.32 9.68 9.66 11.07 9.22
8.63 8.99 JLA198 h-miR-191* 6.30 6.00 6.00 7.24 6.00 6.58 6.63 6.11
6.26 JLA199 h-miR-154* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM316 h-miR-147 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM317 h-miR-155 8.97 9.50 7.69 8.48 9.68 7.96 6.18 6.00 6.00
EAM318 h-miR-17-3p 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA195 h-miR-200a* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA196 h-miR-302a* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
JLA197 h-miR-299-3p 6.41 6.00 6.82 6.00 6.78 7.18 6.47 6.00 6.00
EAM319 h-miR-182* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM405 h-miR-302b 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM406 h-miR-302b* 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.00
EAM392 r-miR-352 6.00 6.00 6.96 6.00 8.26 7.14 6.72 7.48 7.86
JLA123 h-miR-423 6.00 6.00 6.00 6.00 6.00 6.00 6.00 6.39 6.00
JLA124 h-miR-18b 7.00 7.20 6.00 6.00 6.00 7.50 6.00 6.00 6.00 Probe
ID Description MEGA1_2 MEGA1_3 MEGA1_4 MEGA2_1 MEGA2_2 EAM190
h-miR-10b 6.00 6.00 6.00 6.00 6.00 EAM187 hmr-miR-107 6.30 6.68
6.79 6.00 6.00 EAM185 hmr-miR-103 6.76 7.19 7.67 6.44 6.00 EAM181
hmr-let-7f 9.53 8.57 10.11 6.73 8.73 EAM179 hmr-let-7d 9.31 8.27
8.89 9.64 9.34 EAM177 mr-miR-101b 6.00 6.00 6.00 6.00 6.00 EAM175
hmr-miR-320 8.34 8.72 8.73 8.11 8.87 EAM168 hmr-let-7e 6.00 6.00
8.34 6.65 6.00 EAM161 hmr-miR-28 7.96 6.00 8.29 8.44 8.09 EAM160
hmr-miR-26b 9.65 8.59 9.78 8.86 9.24 EAM155 hmr-miR-136 6.00 6.00
6.00 6.00 6.00 EAM283 mr-miR-211 6.00 6.00 6.00 6.00 6.00 EAM282
m-miR-199b 6.00 6.00 6.00 6.00 6.00 EAM281 mr-miR-217 6.00 6.00
6.00 6.00 6.00 EAM280 hmr-miR-30a-3p 6.00 6.00 6.00 6.00 6.00
EAM279 hmr-miR-29c 6.56 6.00 6.00 6.00 6.16 EAM278 hmr-miR-98 8.00
7.69 7.32 8.11 6.00 EAM270 hmr-miR-30b 8.74 8.82 9.46 8.10 8.74
EAM159 hmr-miR-130a 7.39 8.91 6.79 8.20 7.67 EAM163 hmr-miR-142-3p
7.43 6.00 7.89 7.56 6.00 EAM171 hmr-miR-137 6.00 6.00 6.00 6.00
6.00 EAM306 m-miR-201 6.00 6.00 6.00 6.00 6.00 EAM307 m-miR-202
6.00 6.00 6.00 7.21 6.00 EAM308 hmr-miR-206 6.00 6.00 6.00 6.00
6.00 EAM309 m-miR-207 6.00 6.00 7.57 6.00 6.00 EAM310 hmr-miR-208
6.00 6.00 6.00 6.00 6.00 EAM247 hmr-miR-212 6.00 6.00 6.00 6.00
6.00 EAM251 hmr-miR-216 6.00 6.00 6.00 6.00 6.00 EAM253 hmr-miR-218
6.00 6.00 6.00 6.00 6.00 EAM275 hmr-miR-34a 6.00 6.00 6.00 6.00
6.00 EAM246 h-miR-211 6.00 6.00 6.00 6.00 6.00 EAM250 h-miR-215
6.00 6.00 6.00 6.00 6.00 EAM252 h-miR-217 6.00 6.00 6.00 6.00 6.00
EAM224 hmr-miR-17-5p 10.44 11.27 9.91 10.39 8.79 EAM225 hmr-miR-18a
7.40 6.00 6.00 6.00 6.00 EAM226 hmr-miR-181a 7.87 8.68 7.08 6.00
8.81 EAM227 hmr-miR-181b 6.79 7.49 6.00 6.00 6.00 EAM234
hmr-miR-199a 6.00 6.00 6.00 6.00 6.00 EAM235 h-miR-199b 6.00 6.00
6.00 6.00 6.00 EAM236 hmr-miR-19a 7.70 8.90 8.55 6.00 7.14 EAM241
hmr-miR-203 6.00 8.15 6.99 6.00 6.00 EAM242 hmr-miR-204 6.00 6.00
6.00 6.00 6.00 EAM243 hmr-miR-205 6.00 6.00 6.00 6.00 6.00 EAM245
hmr-miR-210 6.00 6.00 6.00 6.00 6.00 EAM249 hmr-miR-214 6.00 6.00
6.00 6.00 6.00 EAM184 hmr-miR-100 6.00 6.00 6.00 6.00 6.00 EAM186
h-miR-106a 10.31 10.92 9.89 10.11 8.23 EAM189 hmr-miR-10a 7.74 8.59
8.29 6.00 6.00 EAM191 hmr-miR-122a 6.00 6.00 6.00 6.00 6.00 EAM192
hmr-miR-126* 6.82 7.25 6.18 6.97 6.00 EAM198 hmr-miR-130b 6.27 6.21
6.00 6.00 6.00 EAM202 hmr-miR-134 6.00 6.00 6.00 6.00 6.00 EAM209
hmr-miR-142-5p 7.81 7.04 7.93 7.90 6.86 EAM221 m-miR-155 7.17 8.01
7.16 6.00 6.00 EAM223 hmr-miR-15b 10.50 10.40 9.74 11.50 11.22
EAM228 hmr-miR-181c 6.00 6.00 6.00 6.00 6.00 EAM222 hm-miR-15a 9.52
9.67 6.00 9.33 6.00 EAM111 hm-let-7g 10.55 10.12 10.44 8.32 9.39
EAM131 hmr-miR-92 10.50 11.33 9.41 9.47 11.07 EAM139 hmr-miR-146a
9.47 10.48 8.86 6.00 8.51 EAM145 hmr-let-7c 8.69 9.07 9.10 7.53
9.60 EAM109 hmr-miR-7 6.00 6.00 6.00 6.00 6.00 EAM152 hm-miR-9*
6.00 6.00 6.00 6.00 6.00 JLA215 hmr-let-7i 8.71 8.89 9.07 9.12 8.59
EAM153 hmr-let-7a 10.98 10.75 11.12 10.65 11.41 EAM147 hmr-let-7b
8.34 7.17 10.57 6.00 6.58 EAM137 hmr-miR-132 6.00 6.95 6.00 6.00
6.00 EAM133 hmr-miR-324-5p 6.00 6.00 6.00 6.00 6.00 EAM103
hmr-miR-124a 6.00 6.00 6.00 6.00 6.00 EAM105 hmr-miR-125b 6.00 7.61
6.00 6.00 6.00 EAM121 hmr-miR-99a 6.00 6.00 6.00 6.00 6.00 EAM115
hmr-miR-16 12.56 12.12 13.06 12.43 12.37 EAM119 hmr-miR-29b 6.00
6.00 6.91 6.00 6.00 EAM311 hmr-miR-101 6.00 6.00 6.00 6.00 6.00
EAM312 h-miR-105 6.00 6.00 6.00 6.00 6.00
EAM313 hmr-miR-106b 8.85 9.53 9.17 8.97 8.11 EAM314 hmr-miR-126
9.23 10.02 9.48 8.22 6.00 EAM315 hmr-miR-127 6.00 6.00 6.00 6.00
6.00 EAM320 hm-miR-189 6.00 6.00 6.00 6.00 6.00 JLA216 hmr-miR-200c
6.00 6.00 6.00 6.96 6.00 EAM323 h-miR-224 6.00 6.00 6.00 6.00 6.00
EAM324 hmr-miR-25 6.85 8.56 6.00 6.00 7.38 EAM386 r-miR-336 6.00
6.00 6.00 6.00 6.00 JLA218 r-miR-343 6.00 6.00 6.00 6.00 6.00
EAM388 r-miR-344 6.00 6.00 6.00 6.00 6.00 EAM338 h-miR-95 6.00 6.00
6.00 6.00 6.00 JLA214 hmr-miR-129 6.00 6.00 6.00 6.00 6.00 EAM340
mr-let-7d* 6.00 6.00 6.00 6.99 6.00 EAM341 m-miR-106a 9.43 10.30
9.16 9.99 8.43 EAM342 hmr-miR-135b 6.00 6.00 6.00 6.00 6.00 EAM343
mr-miR-151 6.00 6.00 6.00 6.00 6.00 EAM344 m-miR-17-3p 6.00 6.00
6.00 6.00 6.00 EAM345 m-miR-224 6.00 6.00 6.00 6.00 6.00 EAM346
mr-miR-290 6.00 6.00 6.00 6.00 6.00 EAM347 mr-miR-291-3p 6.00 6.00
6.00 6.00 6.00 EAM348 mr-miR-291-5p 6.00 6.00 6.00 6.00 6.00 EAM349
mr-miR-292-3p 6.00 6.00 6.00 6.00 6.00 EAM350 mr-miR-292-5p 6.00
6.00 6.00 6.00 6.00 EAM351 m-miR-293 6.00 6.00 6.00 6.00 6.00
EAM352 m-miR-294 6.00 6.00 6.00 6.00 6.00 EAM353 m-miR-295 6.00
6.00 6.00 6.00 6.00 EAM354 m-miR-297 6.00 6.00 6.00 6.00 6.00
EAM355 mr-miR-298 6.00 6.00 6.00 6.00 6.00 EAM356 mr-miR-300 6.00
6.00 6.00 6.00 6.00 EAM358 hmr-miR-323 6.00 6.00 6.49 6.00 6.00
EAM359 hmr-miR-324-3p 6.00 6.00 6.00 6.00 6.00 EAM360 mr-miR-325
6.00 6.63 6.00 6.00 6.00 EAM361 hmr-miR-326 6.00 6.00 6.00 6.00
6.00 EAM362 hmr-miR-328 6.00 6.00 6.00 6.00 6.00 EAM363 mr-miR-329
6.00 6.00 6.00 6.00 6.00 EAM365 hmr-miR-331 6.00 6.00 6.00 6.00
6.00 EAM366 mr-miR-337 6.00 6.00 6.00 6.00 6.00 EAM367 hmr-miR-338
6.00 6.00 6.00 6.00 6.00 EAM368 hmr-miR-339 6.00 6.00 6.00 6.00
6.00 EAM369 hmr-miR-340 6.00 6.00 6.00 6.00 6.00 EAM370 mr-miR-341
6.00 6.00 6.00 6.00 6.00 EAM371 hmr-miR-342 11.21 8.81 10.24 11.01
11.98 EAM372 m-miR-344 6.00 6.00 6.00 6.00 6.00 EAM373 mr-miR-345
6.00 6.00 6.00 6.00 6.00 EAM374 m-miR-346 6.00 6.00 6.00 6.00 6.00
EAM37 mr-miR-34b 6.00 6.00 6.00 6.19 6.00 JLA217 mr-miR-350 6.00
6.00 6.00 6.00 6.00 EAM37 mr-miR-351 6.00 6.00 6.00 6.00 6.00 EAM37
mr-miR-7b 6.00 6.00 6.00 6.00 6.00 EAM38 r-miR-20* 6.00 6.00 6.00
6.00 6.00 EAM38 r-miR-327 6.00 6.00 6.00 6.00 6.00 EAM38 r-miR-333
6.00 6.00 6.00 6.00 6.00 EAM38 hmr-miR-335 7.18 7.80 6.00 6.00 6.00
EAM39 r-miR-7* 6.00 6.00 6.00 6.00 6.00 EAM30 hmr-miR-200a 6.00
6.00 6.00 6.00 6.00 EAM29 hmr-miR-194 6.00 6.22 6.00 6.00 6.00
JLA221 hmr-miR-191 8.20 7.45 8.85 7.58 8.83 EAM29 hmr-miR-190 6.00
6.00 6.00 6.00 6.00 EAM29 hmr-miR-186 6.00 6.00 6.00 6.00 6.00
JLA219 hmr-miR-185 6.00 6.00 6.00 6.00 6.00 EAM29 hmr-miR-184 6.00
6.00 6.00 6.00 6.00 EAM40 hm-miR-133b 6.00 6.00 6.00 6.94 6.00
EAM40 h-miR-151 6.00 6.00 6.00 6.00 6.00 EAM40 hmr-miR-196b 6.00
6.00 6.00 6.00 6.00 EAM41 hm-miR-370 6.00 6.00 6.00 6.00 6.00 EAM41
h-miR-371 6.00 6.00 6.00 6.00 6.00 EAM42 h-miR-372 6.00 6.00 6.00
6.00 6.00 EAM42 h-miR-373 6.00 6.00 6.00 6.00 6.00 EAM42 h-miR-373*
6.00 6.00 6.00 6.00 6.00 EAM42 h-miR-374 6.00 7.84 6.58 6.50 6.70
EAM42 m-miR-215 6.00 6.00 6.00 6.00 6.00 EAM42 hm-miR-409-3p 6.80
6.00 6.00 6.00 6.00 EAM42 hm-miR-410 6.00 6.00 6.00 6.00 6.00 EAM42
m-miR-376b 6.00 6.00 6.00 6.00 6.00 EAM43 m-miR-376a 6.00 6.00 6.00
6.00 6.00 EAM43 m-miR-411 6.00 6.00 6.00 6.00 6.00 EAM43
m-miR-380-3p 6.00 6.00 6.00 6.00 6.00 EAM43 hm-miR-412 6.00 6.00
6.00 6.00 6.00 EAM26 hmr-miR-27b 6.46 8.12 7.01 7.72 6.00 EAM26
hmr-miR-26a 10.10 10.36 9.80 10.53 10.61 EAM26 hmr-miR-24 6.06 6.00
6.00 6.00 8.19 EAM26 hmr-miR-23b 8.76 8.71 8.23 9.80 9.82 EAM26
hmr-miR-23a 8.70 9.13 8.70 9.58 9.49 EAM25 h-miR-220 6.00 6.00 6.00
6.00 6.00 EAM25 hmr-miR-22 6.00 6.00 6.00 6.00 6.00 EAM24
hmr-miR-213 6.00 6.00 6.00 6.00 6.00 EAM24 hmr-miR-21 8.75 9.03
10.40 10.10 6.00 EAM24 hmr-miR-20a 11.01 11.25 10.42 10.12 8.35
EAM23 hmr-miR-19b 7.94 9.23 8.64 6.80 7.05 EAM23 hmr-miR-196a 6.00
6.00 6.00 6.00 6.00 EAM hm-miR-148a 6.00 6.00 6.00 6.00 6.00 EAM21
hmr-miR-145 6.00 6.16 6.00 7.14 6.00 EAM21 hmr-miR-144 7.20 6.00
6.00 7.46 6.88 EAM hmr-miR-143 6.00 6.00 6.00 6.00 6.00 EAM38
r-miR-346 6.00 6.00 6.00 6.00 6.00 EAM39 r-miR-347 6.00 6.00 6.00
6.00 6.00 EAM39 r-miR-349 6.00 6.00 6.00 6.00 6.00 JLA223
hmr-miR-33 6.00 6.00 6.00 6.00 6.00 EAM27 hmr-miR-96 6.00 6.00 6.00
6.00 6.00 EAM27 hmr-miR-9 6.00 6.00 6.00 6.00 6.00 EAM27
hmr-miR-30d 7.77 7.93 7.87 7.45 7.53 EAM28 mr-miR-10b 7.30 7.23
6.00 6.00 6.00 EAM29 hm-miR-188 6.00 6.00 6.00 6.00 6.00 EAM29
hmr-miR-193a 6.00 6.00 6.00 6.00 6.00 EAM30 h-miR-198 6.00 6.00
6.00 6.00 6.00 EAM23 hmr-miR-192 6.00 6.00 6.00 6.00 6.00 EAM23
hmr-miR-187 6.00 6.00 6.00 6.00 6.00 EAM23 hmr-miR-183 6.00 6.00
6.00 6.00 6.00 EAM22 hm-miR-182 6.00 6.00 6.00 6.00 6.00 EAM
hmr-miR-154 6.00 6.00 6.00 6.39 6.00 EAM hmr-miR-153 6.00 6.00 6.00
6.00 6.00 EAM hmr-miR-152 6.00 6.00 6.00 6.00 6.00 EAM21
hmr-miR-150 11.16 6.00 9.51 11.36 12.16 EAM hm-miR-149 6.00 6.00
6.00 6.00 6.00 EAM hmr-miR-148b 6.00 6.00 6.00 6.00 6.00 EAM
hmr-miR-30c 8.38 8.74 9.34 8.39 8.71 EAM26 hmr-miR-29a 8.05 6.00
6.00 6.00 7.29 EAM30 hmr-miR-200b 6.00 6.23 6.00 6.00 6.00 EAM30
hm-miR-199a* 6.00 6.00 6.00 6.00 6.00 EAM30 h-miR-197 7.57 6.00
6.61 8.15 10.15 EAM29 hmr-miR-195 8.90 8.67 10.18 9.61 9.73 JLA91
hmr-miR-99b 6.00 6.00 9.02 6.00 6.00 JLA92 hmr-miR-433 6.00 6.00
6.00 6.00 6.00 JLA93 hmr-miR-431 6.00 6.00 6.00 7.98 6.00 JLA94
hmr-miR-365 6.77 6.53 6.00 9.78 6.00 JLA95 hmr-miR-450 6.00 6.00
6.00 6.00 6.00 JLA96 hmr-miR-449 6.00 6.00 6.00 6.00 6.00 JLA99
hmr-miR-448 6.00 6.00 6.00 6.00 6.00 JLA103 hmr-miR-424 7.35 7.34
6.00 6.00 7.82 JLA105 hm-miR-361 6.00 6.98 7.83 6.00 6.00 JLA106
hm-miR-375 6.00 6.00 6.00 6.00 6.00 JLA107 hm-miR-377 6.00 6.78
6.00 6.00 6.00 JLA108 hm-miR-378 6.00 6.00 6.00 6.00 6.00 JLA109
hm-miR-379 6.00 6.00 6.00 6.00 6.00 JLA110 hm-miR-380-5p 6.00 6.00
6.00 6.00 6.00 JLA111 hm-miR-381 6.00 6.00 6.00 6.00 6.00 JLA112
hm-miR-382 6.00 6.00 6.00 7.52 6.00 JLA115 hm-miR-384 6.00 6.00
6.00 6.00 6.00 JLA116 hm-miR-425 6.00 6.00 6.00 6.00 6.00 JLA117
hm-miR-452 6.00 6.00 6.00 6.00 6.00 JLA118 hm-miR-30e-3p 6.00 6.00
6.00 6.00 6.00 JLA104 mr-miR-129-3p 8.05 6.65 6.00 10.17 6.00 JLA98
mr-miR-429 6.00 6.00 6.00 6.00 6.00 JLA101 mr-miR-330 6.00 6.00
6.00 6.00 6.00 JLA102 mr-miR-322 6.00 6.00 6.00 6.00 6.00 JLA114
m-miR-383 6.00 6.00 6.00 6.00 6.00 JLA5 hmr-miR-451 8.40 6.00 6.13
7.43 9.12 JLA201 r-miR-421 6.00 6.00 6.00 6.00 6.00 JLA202
m-miR-463 6.00 6.00 6.00 6.00 6.00 JLA203 m-miR-464 6.00 6.00 6.00
6.00 6.00 JLA204 m-miR-465 6.00 6.00 6.00 6.00 6.00 JLA205
m-miR-466 6.00 6.00 6.00 6.00 6.00 JLA206 m-miR-467 6.00 6.00 6.00
6.00 6.00 JLA207 m-miR-468 6.00 6.00 6.00 6.00 6.00 JLA208
m-miR-469 6.00 6.00 6.00 6.00 6.00 JLA209 m-miR-470 6.00 6.00 6.00
6.00 6.00 JLA210 m-miR-471 6.00 6.00 6.00 6.00 6.00 EAM325
hmr-miR-27a 7.10 8.39 6.53 8.76 6.00 EAM326 hmr-miR-296 6.00 6.00
6.00 6.00 6.00 EAM327 hmr-miR-299-5p 6.00 6.00 6.00 6.00 6.00
EAM328 hmr-miR-301 6.00 6.00 6.00 6.00 6.00 EAM329 hm-miR-302a 6.00
6.00 6.00 6.00 6.00 EAM330 hmr-miR-30a-5p 6.00 6.00 6.00 6.00 6.00
EAM331 hmr-miR-30e-5p 6.00 7.15 6.00 6.00 6.00 EAM332 hmr-miR-31
6.00 6.00 6.00 6.00 6.00 EAM333 hmr-miR-32 6.00 6.00 6.00 6.00 6.00
EAM335 h-miR-34b 6.00 6.00 6.00 6.00 6.00 EAM336 hmr-miR-34c 6.00
6.00 6.00 6.00 6.00 EAM337 hmr-miR-93 8.55 9.94 9.41 7.91 6.00
EAM208 hmr-miR-141 6.00 6.00 6.00 6.00 6.00 EAM207 hmr-miR-140 6.00
6.00 6.00 6.00 6.00 JLA222 hmr-miR-139 6.00 6.00 6.00 6.00 6.00
JLA220 hmr-miR-138 6.00 6.00 6.00 6.00 6.00 EAM203 hmr-miR-135a
6.00 6.00 6.00 6.00 6.00 EAM200 hmr-miR-133a 6.00 6.00 6.00 6.99
6.00 EAM195 hmr-miR-128b 6.00 6.00 6.00 6.00 6.00 EAM194
hmr-miR-128a 6.00 6.00 6.00 6.00 6.00 EAM254 hmr-miR-219 6.00 6.00
6.00 6.00 6.00 EAM257 hmr-miR-221 7.37 7.46 6.00 8.97 8.93 EAM258
hmr-miR-222 8.32 7.76 6.95 8.78 6.00 EAM259 hmr-miR-223 8.60 8.36
9.22 9.19 8.58 JLA211 m-miR-434-5p 6.00 6.00 6.00 6.00 6.00 JLA212
m-miR-434-3p 6.00 6.00 6.00 6.00 6.00 JLA213 m-miR-433-5p 6.00 6.00
6.00 6.00 6.00 JLA2 hsa-miR-522 6.00 6.00 6.00 6.00 6.00 JLA3
hsa-miR-495 6.00 6.00 6.00 6.00 6.00 JLA200 r-miR-297 6.00 6.00
6.00 6.00 6.00 JLA6 hsa-miR-518e 6.00 6.00 6.00 6.00 6.00 JLA7
hsa-miR-519a 6.00 6.00 6.00 6.00 6.00 JLA8 hsa-mir-527* 6.00 6.00
6.00 6.00 6.00 JLA72 hmr-miR-140* 6.03 6.02 6.00 8.06 6.00 JLA10
hsa-miR-521 6.00 6.00 6.00 6.00 6.00 JLA12 hsa-miR-362 6.00 6.00
6.00 6.00 6.00 JLA74 hsa-mir-18* 6.00 6.00 6.00 6.39 6.00 JLA14
hm-miR-363 6.00 6.00 7.63 6.00 6.00 JLA77 hsa-mir-19b-1* 6.00 6.00
6.00 6.00 6.00 JLA17 hsa-mir-520c,b,f 6.00 6.00 6.00 6.00 6.00
JLA79 hsa-mir-23a* 6.00 6.00 6.00 6.00 6.00 JLA20 hsa-miR-369-5p
6.00 6.00 6.00 6.00 6.00 JLA81 hsa-mir-339* 6.00 6.00 6.00 6.00
6.00 JLA23 hsa-mir-342* 6.00 6.81 6.00 8.42 7.43 JLA24 hsa-mir-19a*
6.00 6.00 6.00 6.00 6.00 JLA26 hsa-miR-517a,b 6.00 6.00 6.00 6.00
6.00 JLA27 hsa-miR-516-5p 6.00 6.00 6.00 6.00 6.00 JLA28
hsa-miR-518b 6.00 6.00 6.00 6.00 6.00 JLA29 hsa-miR-519d 6.00 6.00
6.00 6.00 6.00 JLA73 hr-mir-151* 7.22 6.01 7.57 6.87 8.90 JLA31
hsa-mir-28* 6.00 6.00 6.00 6.00 6.00 JLA33 hsa-mir-519a-2* 6.00
6.00 6.00 6.00 6.00 JLA34 hsa-mir-26b* 6.00 6.00 6.00 6.00 6.00
JLA35 hsa-miR-526c 6.00 6.00 6.00 6.00 6.00 JLA36 hsa-miR-527 6.00
6.00 6.00 6.00 6.00 JLA38 hsa-mir-29b-2* 6.00 6.00 6.00 6.00 6.00
JLA39 hsa-let-7g* 6.00 6.00 6.00 6.00 6.00 JLA40 hsa-miR-518a 6.00
6.00 6.00 6.00 6.00 JLA41 hsa-miR-523 6.00 6.00 6.00 6.00 6.00
JLA44 hsa-miR-515-3p 6.00 6.00 6.00 6.00 6.00 JLA45 hsa-mir-146b*
6.00 6.00 6.00 6.00 6.00 JLA49 hsa-mir-222* 6.00 6.00 6.00 6.00
6.00 JLA53 hsa-mir-24* 6.00 6.00 6.00 6.00 6.00 JLA55 hsa-miR-503
6.00 6.00 6.00 6.00 6.00 JLA57 hsa-mir-505 6.00 6.00 6.00 6.00 6.00
JLA82 hsa-mir-423* 10.16 9.82 9.90 11.38 12.04 JLA66 hsa-miR-432
6.00 7.28 6.00 6.00 6.00 JLA83 hsa-mir-425* 7.93 7.46 6.00 6.51
6.00 JLA84 hsa-mir-92-1* 6.00 6.00 6.00 6.00 6.00 JLA69
hsa-mir-193* 6.00 6.00 6.00 6.00 6.00 JLA70 hsa-miR-515-5p 6.00
6.00 6.00 6.00 6.00 JLA71 hsa-mir-516-1* 6.00 6.00 6.00 6.00 6.00
JLA85 hsa-mir-30d* 6.00 6.00 6.00 6.00 6.00 JLA125 h-miR-20b 9.71
9.91 8.67 8.72 8.40 JLA198 h-miR-191* 6.00 6.00 6.74 6.36 6.15
JLA199 h-miR-154* 6.00 6.00 6.00 6.00 6.00 EAM316 h-miR-147 6.00
6.00 6.00 6.00 6.00 EAM317 h-miR-155 8.85 9.85 8.50 6.00 6.00
EAM318 h-miR-17-3p 6.00 6.00 6.00 6.00 6.00 JLA195 h-miR-200a* 6.00
6.00 6.00 6.00 6.00 JLA196 h-miR-302a* 6.00 6.00 6.00 6.00 6.00
JLA197 h-miR-299-3p 6.00 6.00 6.00 6.23 6.00 EAM319 h-miR-182* 6.00
6.00 6.00 6.00 6.00 EAM405 h-miR-302b 6.00 6.00 6.00 6.00 6.00
EAM406 h-miR-302b* 6.00 6.00 6.00 6.00 6.00 EAM392 r-miR-352 7.72
6.58 7.71 8.32 7.78 JLA123 h-miR-423 6.00 6.00 6.00 6.00 6.00
JLA124 h-miR-18b 7.19 6.00 6.00 6.00 6.00 Probe ID Description
MEGA2_3 MEGA2_4 MEGA2_5 MEGA2_6 EAM190 h-miR-10b 6.66 6.00 6.00
7.22 EAM187 hmr-miR-107 8.32 7.63 6.92 8.79 EAM185 hmr-miR-103 8.54
8.04 7.13 9.39
EAM181 hmr-let-7f 9.75 8.60 9.07 9.57 EAM179 hmr-let-7d 9.91 9.61
9.83 9.79 EAM177 mr-miR-101b 6.00 6.00 6.00 6.00 EAM175 hmr-miR-320
8.50 8.70 7.50 7.51 EAM168 hmr-let-7e 6.00 6.00 6.00 7.50 EAM161
hmr-miR-28 8.01 7.47 6.00 8.47 EAM160 hmr-miR-26b 9.38 9.23 8.61
8.95 EAM155 hmr-miR-136 6.00 6.00 6.00 6.00 EAM283 mr-miR-211 6.00
6.00 6.00 6.00 EAM282 m-miR-199b 6.00 6.00 6.00 6.00 EAM281
mr-miR-217 6.00 6.00 6.00 6.00 EAM280 hmr-miR-30a-3p 6.00 6.00 6.00
6.00 EAM279 hmr-miR-29c 8.18 7.23 6.00 6.00 EAM278 hmr-miR-98 6.00
7.17 9.06 6.50 EAM270 hmr-miR-30b 9.66 9.54 6.00 9.43 EAM159
hmr-miR-130a 7.48 6.87 6.00 6.00 EAM163 hmr-miR-142-3p 7.79 7.27
8.56 6.00 EAM171 hmr-miR-137 6.00 6.00 6.00 6.00 EAM306 m-miR-201
6.00 6.00 6.00 6.00 EAM307 m-miR-202 6.00 6.00 7.05 6.00 EAM308
hmr-miR-206 6.00 6.00 6.00 6.00 EAM309 m-miR-207 6.00 6.00 6.00
6.00 EAM310 hmr-miR-208 6.00 6.00 6.00 6.00 EAM247 hmr-miR-212 6.00
6.00 6.00 6.00 EAM251 hmr-miR-216 6.00 6.00 6.00 6.00 EAM253
hmr-miR-218 6.00 6.00 6.00 6.00 EAM275 hmr-miR-34a 6.00 6.00 6.00
6.00 EAM246 h-miR-211 6.00 6.00 6.00 6.00 EAM250 h-miR-215 6.00
6.00 7.32 6.00 EAM252 h-miR-217 6.00 6.00 6.00 6.00 EAM224
hmr-miR-17-5p 10.13 10.33 9.48 9.88 EAM225 hmr-miR-18a 6.00 6.00
6.00 6.00 EAM226 hmr-miR-181a 6.84 9.72 6.00 6.56 EAM227
hmr-miR-181b 6.00 7.54 6.00 6.00 EAM234 hmr-miR-199a 6.00 6.00 6.00
6.00 EAM235 h-miR-199b 6.00 6.00 6.00 6.00 EAM236 hmr-miR-19a 6.00
7.61 8.19 6.60 EAM241 hmr-miR-203 6.00 6.00 8.16 6.00 EAM242
hmr-miR-204 6.00 6.00 6.00 6.00 EAM243 hmr-miR-205 6.00 6.00 6.00
6.00 EAM245 hmr-miR-210 6.00 6.00 6.00 6.00 EAM249 hmr-miR-214 6.00
6.00 6.00 6.12 EAM184 hmr-miR-100 6.00 6.00 7.20 6.00 EAM186
h-miR-106a 10.12 10.01 9.48 9.71 EAM189 hmr-miR-10a 6.00 6.72 6.00
6.00 EAM191 hmr-miR-122a 6.00 6.00 6.00 6.00 EAM192 hmr-miR-126*
6.00 6.00 6.00 7.21 EAM198 hmr-miR-130b 6.00 6.00 6.00 6.00 EAM202
hmr-miR-134 6.00 6.00 6.00 6.00 EAM209 hmr-miR-142-5p 8.66 8.37
9.90 7.87 EAM221 m-miR-155 7.48 6.00 6.00 7.03 EAM223 hmr-miR-15b
10.39 10.79 11.03 11.04 EAM228 hmr-miR-181c 6.00 6.00 6.00 6.00
EAM222 hm-miR-15a 8.87 10.18 10.57 8.69 EAM111 hm-let-7g 11.19
10.14 10.65 10.03 EAM131 hmr-miR-92 9.10 10.74 9.01 10.31 EAM139
hmr-miR-146a 9.66 8.61 6.00 8.90 EAM145 hmr-let-7c 7.46 6.68 9.21
7.82 EAM109 hmr-miR-7 6.00 6.00 6.00 6.00 EAM152 hm-miR-9* 6.00
6.00 6.00 6.00 JLA215 hmr-let-7i 8.08 9.20 10.60 9.03 EAM153
hmr-let-7a 10.93 10.44 11.51 11.17 EAM147 hmr-let-7b 6.09 6.78 9.59
6.11 EAM137 hmr-miR-132 6.00 6.00 6.00 6.00 EAM133 hmr-miR-324-5p
6.00 7.17 6.00 6.00 EAM103 hmr-miR-124a 6.00 6.00 6.00 6.00 EAM105
hmr-miR-125b 6.00 6.00 6.00 6.00 EAM121 hmr-miR-99a 6.00 6.00 6.00
6.00 EAM115 hmr-miR-16 12.79 12.11 13.02 12.69 EAM119 hmr-miR-29b
6.00 7.01 6.00 6.00 EAM311 hmr-miR-101 6.00 6.00 6.00 6.00 EAM312
h-miR-105 6.00 6.00 6.00 6.00 EAM313 hmr-miR-106b 9.38 8.94 7.61
8.82 EAM314 hmr-miR-126 8.38 8.42 6.00 8.73 EAM315 hmr-miR-127 6.00
6.00 6.00 6.00 EAM320 hm-miR-189 6.00 6.00 6.00 6.00 JLA216
hmr-miR-200c 7.14 6.52 7.22 6.00 EAM323 h-miR-224 6.00 6.00 6.00
6.00 EAM324 hmr-miR-25 6.00 7.51 6.00 6.00 EAM386 r-miR-336 6.00
6.00 6.00 6.00 JLA218 r-miR-343 6.00 6.00 6.00 6.00 EAM388
r-miR-344 6.00 6.00 6.00 6.00 EAM338 h-miR-95 6.00 6.00 6.00 6.00
JLA214 hmr-miR-129 6.00 6.00 6.00 6.00 EAM340 mr-let-7d* 6.00 6.00
6.00 6.00 EAM341 m-miR-106a 9.69 9.84 7.93 9.04 EAM342 hmr-miR-135b
6.00 6.00 6.00 6.00 EAM343 mr-miR-151 6.00 6.00 6.00 6.00 EAM344
m-miR-17-3p 6.00 6.00 6.00 6.00 EAM345 m-miR-224 6.00 6.00 6.00
6.00 EAM346 mr-miR-290 6.00 6.00 6.00 6.00 EAM347 mr-miR-291-3p
6.00 6.00 6.00 6.00 EAM348 mr-miR-291-5p 6.00 6.00 6.00 6.00 EAM349
mr-miR-292-3p 6.00 6.00 6.00 6.00 EAM350 mr-miR-292-5p 6.00 6.00
6.00 6.00 EAM351 m-miR-293 6.00 6.00 6.00 6.00 EAM352 m-miR-294
6.00 6.00 6.00 6.00 EAM353 m-miR-295 6.00 6.00 6.00 6.00 EAM354
m-miR-297 6.00 6.00 6.00 6.00 EAM355 mr-miR-298 7.52 6.00 6.00 6.00
EAM356 mr-miR-300 6.00 6.00 6.00 6.00 EAM358 hmr-miR-323 6.00 6.00
6.00 6.00 EAM359 hmr-miR-324-3p 6.00 6.00 6.00 6.00 EAM360
mr-miR-325 6.00 6.00 6.00 6.00 EAM361 hmr-miR-326 6.00 6.00 6.00
6.00 EAM362 hmr-miR-328 6.00 6.00 6.00 6.00 EAM363 mr-miR-329 6.00
6.00 6.00 6.00 EAM365 hmr-miR-331 6.00 6.00 6.00 6.00 EAM366
mr-miR-337 6.00 6.00 6.00 6.00 EAM367 hmr-miR-338 6.00 6.00 6.00
6.00 EAM368 hmr-miR-339 6.00 6.00 6.00 6.00 EAM369 hmr-miR-340 6.00
6.00 6.00 6.00 EAM370 mr-miR-341 6.00 6.00 6.00 6.00 EAM371
hmr-miR-342 10.79 11.69 11.33 11.20 EAM372 m-miR-344 6.00 6.00 6.00
6.00 EAM373 mr-miR-345 6.00 6.00 6.00 6.00 EAM374 m-miR-346 6.00
6.00 6.00 6.00 EAM37 mr-miR-34b 6.00 6.00 6.00 6.00 JLA217
mr-miR-350 6.00 6.00 6.00 6.00 EAM37 mr-miR-351 6.00 6.00 6.00 6.00
EAM37 mr-miR-7b 6.00 6.00 6.00 6.00 EAM38 r-miR-20* 6.00 6.00 6.00
6.00 EAM38 r-miR-327 6.00 6.00 6.00 6.00 EAM38 r-miR-333 6.00 6.00
6.00 6.00 EAM38 hmr-miR-335 6.42 6.00 6.00 6.00 EAM39 r-miR-7* 6.00
6.00 6.00 6.00 EAM30 hmr-miR-200a 6.00 6.00 6.00 6.00 EAM29
hmr-miR-194 6.00 6.00 6.00 6.00 JLA221 hmr-miR-191 7.67 8.32 8.13
8.89 EAM29 hmr-miR-190 6.00 6.00 6.00 6.00 EAM29 hmr-miR-186 6.00
6.00 6.00 6.00 JLA219 hmr-miR-185 6.00 7.40 6.00 6.00 EAM29
hmr-miR-184 6.00 7.33 6.00 6.00 EAM40 hm-miR-133b 6.00 6.00 6.00
6.00 EAM40 h-miR-151 6.00 6.00 6.00 6.00 EAM40 hmr-miR-196b 6.00
6.00 6.00 6.00 EAM41 hm-miR-370 6.00 6.00 6.00 6.00 EAM41 h-miR-371
6.00 6.00 6.00 6.00 EAM42 h-miR-372 6.00 6.00 6.00 6.00 EAM42
h-miR-373 6.00 6.00 6.00 6.00 EAM42 h-miR-373* 6.00 6.00 6.00 6.00
EAM42 h-miR-374 6.78 7.50 6.00 6.82 EAM42 m-miR-215 6.00 6.00 6.00
6.00 EAM42 hm-miR-409-3p 6.00 6.00 6.00 6.00 EAM42 hm-miR-410 6.00
6.00 6.00 6.00 EAM42 m-miR-376b 6.00 6.00 6.00 6.00 EAM43
m-miR-376a 6.00 6.00 6.00 6.00 EAM43 m-miR-411 6.00 6.00 6.00 6.00
EAM43 m-miR-380-3p 6.00 6.00 6.00 6.00 EAM43 hm-miR-412 6.00 6.00
6.00 6.00 EAM26 hmr-miR-27b 6.48 6.42 6.00 6.00 EAM26 hmr-miR-26a
10.61 10.21 9.69 10.16 EAM26 hmr-miR-24 6.00 7.34 6.00 7.32 EAM26
hmr-miR-23b 8.30 9.41 7.07 9.69 EAM26 hmr-miR-23a 7.88 9.15 7.55
9.76 EAM25 h-miR-220 6.00 6.00 6.11 6.00 EAM25 hmr-miR-22 6.00 6.82
6.00 6.00 EAM24 hmr-miR-213 6.00 6.00 6.00 6.00 EAM24 hmr-miR-21
9.43 9.46 8.42 9.73 EAM24 hmr-miR-20a 10.58 9.97 10.81 10.61 EAM23
hmr-miR-19b 6.00 8.35 8.53 7.39 EAM23 hmr-miR-196a 6.00 6.00 6.00
6.00 EAM hm-miR-148a 6.05 6.00 6.00 6.00 EAM21 hmr-miR-145 6.00
6.00 6.00 6.00 EAM21 hmr-miR-144 6.00 6.17 9.44 7.76 EAM
hmr-miR-143 6.00 6.00 6.00 6.00 EAM38 r-miR-346 6.00 6.00 6.00 6.00
EAM39 r-miR-347 6.00 6.00 6.00 6.00 EAM39 r-miR-349 6.00 6.00 6.00
6.00 JLA223 hmr-miR-33 6.00 6.00 6.00 6.00 EAM27 hmr-miR-96 6.00
6.00 6.00 6.00 EAM27 hmr-miR-9 6.00 6.00 6.00 6.00 EAM27
hmr-miR-30d 6.00 8.04 7.48 6.00 EAM28 mr-miR-10b 7.97 6.00 6.00
7.89 EAM29 hm-miR-188 6.00 6.00 6.00 6.00 EAM29 hmr-miR-193a 6.00
6.00 6.00 6.00 EAM30 h-miR-198 6.00 6.00 6.00 6.00 EAM23
hmr-miR-192 6.00 6.00 8.50 6.00 EAM23 hmr-miR-187 6.00 6.00 6.00
6.00 EAM23 hmr-miR-183 6.00 6.00 8.16 6.00 EAM22 hm-miR-182 6.00
6.00 6.00 6.48 EAM hmr-miR-154 6.00 6.00 6.00 6.00 EAM hmr-miR-153
6.00 6.00 6.00 6.00 EAM hmr-miR-152 6.00 6.00 6.00 6.00 EAM21
hmr-miR-150 11.59 11.15 9.72 10.24 EAM hm-miR-149 6.00 6.00 6.00
6.00 EAM hmr-miR-148b 7.27 6.00 6.00 6.00 EAM hmr-miR-30c 9.24 9.92
6.00 9.42 EAM26 hmr-miR-29a 9.38 8.34 6.29 6.00 EAM30 hmr-miR-200b
6.51 6.00 6.00 6.00 EAM30 hm-miR-199a* 6.00 6.00 6.00 6.00 EAM30
h-miR-197 6.98 9.26 7.21 8.36 EAM29 hmr-miR-195 9.28 8.75 10.26
9.42 JLA91 hmr-miR-99b 6.00 7.63 9.71 6.00 JLA92 hmr-miR-433 6.00
6.00 6.00 6.00 JLA93 hmr-miR-431 6.00 6.00 6.00 6.00 JLA94
hmr-miR-365 6.79 6.00 6.00 9.08 JLA95 hmr-miR-450 6.00 6.00 6.00
6.00 JLA96 hmr-miR-449 6.00 6.00 6.00 6.00 JLA99 hmr-miR-448 6.00
6.00 6.00 6.00 JLA103 hmr-miR-424 6.00 6.20 6.00 7.17 JLA105
hm-miR-361 6.23 7.28 6.00 6.00 JLA106 hm-miR-375 6.00 6.00 6.00
6.00 JLA107 hm-miR-377 6.00 6.19 6.00 6.00 JLA108 hm-miR-378 6.00
6.00 6.00 6.00 JLA109 hm-miR-379 6.00 6.00 6.00 6.00 JLA110
hm-miR-380-5p 6.00 6.00 6.00 6.00 JLA111 hm-miR-381 6.00 6.00 6.00
6.00 JLA112 hm-miR-382 6.00 7.61 6.00 6.00 JLA115 hm-miR-384 6.00
6.00 6.00 6.00 JLA116 hm-miR-425 6.00 6.00 6.00 6.00 JLA117
hm-miR-452 6.00 6.00 6.00 6.00 JLA118 hm-miR-30e-3p 6.36 6.00 6.00
6.00 JLA104 mr-miR-129-3p 6.00 6.00 9.32 7.47 JLA98 mr-miR-429 6.00
6.00 6.00 6.00 JLA101 mr-miR-330 6.00 6.00 6.00 6.00 JLA102
mr-miR-322 6.00 6.00 6.00 6.00 JLA114 m-miR-383 6.00 6.00 6.00 6.00
JLA5 hmr-miR-451 9.14 7.74 7.56 7.28 JLA201 r-miR-421 6.00 6.00
6.00 6.00 JLA202 m-miR-463 6.00 6.00 6.00 6.00 JLA203 m-miR-464
6.00 6.00 6.00 6.00 JLA204 m-miR-465 6.00 6.00 6.00 6.00 JLA205
m-miR-466 6.00 6.00 6.00 6.00 JLA206 m-miR-467 6.00 6.00 6.00 6.00
JLA207 m-miR-468 6.00 6.00 6.00 6.00 JLA208 m-miR-469 6.00 6.00
6.00 6.00 JLA209 m-miR-470 6.00 6.00 6.00 6.00 JLA210 m-miR-471
6.00 6.00 6.00 6.00 EAM325 hmr-miR-27a 6.63 7.02 6.00 6.84 EAM326
hmr-miR-296 6.00 6.00 6.00 6.00 EAM327 hmr-miR-299-5p 6.00 6.00
6.00 6.00 EAM328 hmr-miR-301 6.09 6.00 6.00 6.00 EAM329 hm-miR-302a
6.00 6.00 6.00 6.00 EAM330 hmr-miR-30a-5p 6.29 6.00 6.00 6.00
EAM331 hmr-miR-30e-5p 7.02 6.00 6.00 6.00 EAM332 hmr-miR-31 6.00
6.00 6.00 6.00 EAM333 hmr-miR-32 6.00 6.00 6.00 6.00 EAM335
h-miR-34b 6.00 6.00 6.00 6.00 EAM336 hmr-miR-34c 6.00 6.00 6.00
6.00 EAM337 hmr-miR-93 9.76 9.69 8.17 8.93 EAM208 hmr-miR-141 6.00
6.00 6.00 6.00 EAM207 hmr-miR-140 6.00 6.00 6.00 6.00 JLA222
hmr-miR-139 6.00 6.00 6.00 6.00 JLA220 hmr-miR-138 6.00 6.00 6.00
6.00 EAM203 hmr-miR-135a 6.00 6.00 6.00 6.00 EAM200 hmr-miR-133a
6.00 6.00 6.00 6.00 EAM195 hmr-miR-128b 6.00 6.00 6.00 6.00 EAM194
hmr-miR-128a 6.00 6.00 6.00 6.00 EAM254 hmr-miR-219 6.00 6.00 6.00
6.00 EAM257 hmr-miR-221 6.00 6.00 6.00 6.00
EAM258 hmr-miR-222 6.00 6.83 6.00 6.00 EAM259 hmr-miR-223 8.02 8.85
6.64 9.70 JLA211 m-miR-434-5p 6.00 6.00 6.00 6.00 JLA212
m-miR-434-3p 6.00 6.00 6.00 6.00 JLA213 m-miR-433-5p 6.00 6.00 6.00
6.00 JLA2 hsa-miR-522 6.00 6.00 6.00 6.00 JLA3 hsa-miR-495 6.00
6.00 6.00 6.00 JLA200 r-miR-297 6.00 6.00 6.00 6.00 JLA6
hsa-miR-518e 6.00 6.00 6.00 6.00 JLA7 hsa-miR-519a 6.00 6.00 6.00
6.00 JLA8 hsa-mir-527* 6.00 6.00 6.00 6.00 JLA72 hmr-miR-140* 6.93
7.57 6.48 6.93 JLA10 hsa-miR-521 6.00 6.00 6.00 6.00 JLA12
hsa-miR-362 6.00 6.00 6.00 6.00 JLA74 hsa-mir-18* 6.00 6.00 6.00
6.00 JLA14 hm-miR-363 6.00 7.63 6.00 6.00 JLA77 hsa-mir-19b-1* 6.00
6.00 6.00 6.00 JLA17 hsa-mir-520c,b,f 6.00 6.00 6.00 6.00 JLA79
hsa-mir-23a* 6.57 6.00 6.00 7.64 JLA20 hsa-miR-369-5p 6.00 6.00
6.00 6.00 JLA81 hsa-mir-339* 6.00 6.00 6.00 6.00 JLA23 hsa-mir-342*
6.00 6.00 7.48 6.00 JLA24 hsa-mir-19a* 6.00 6.00 6.00 6.00 JLA26
hsa-miR-517a,b 6.00 6.00 6.00 6.00 JLA27 hsa-miR-516-5p 6.00 6.00
6.00 6.00 JLA28 hsa-miR-518b 6.00 6.00 6.00 6.00 JLA29 hsa-miR-519d
6.00 6.00 6.00 6.00 JLA73 hr-mir-151* 7.45 7.30 6.00 7.78 JLA31
hsa-mir-28* 6.00 6.00 6.00 6.00 JLA33 hsa-mir-519a-2* 6.00 6.00
6.00 6.00 JLA34 hsa-mir-26b* 6.00 6.00 6.00 6.00 JLA35 hsa-miR-526c
6.00 6.00 6.00 6.00 JLA36 hsa-miR-527 6.00 6.00 6.00 6.00 JLA38
hsa-mir-29b-2* 6.00 6.00 6.00 6.00 JLA39 hsa-let-7g* 6.00 6.00 6.00
6.00 JLA40 hsa-miR-518a 6.00 6.00 6.00 6.00 JLA41 hsa-miR-523 6.00
6.00 6.00 6.00 JLA44 hsa-miR-515-3p 6.00 6.00 6.00 6.00 JLA45
hsa-mir-146b* 6.00 6.00 6.00 6.00 JLA49 hsa-mir-222* 6.00 6.00 6.00
6.00 JLA53 hsa-mir-24* 6.00 6.00 6.00 6.00 JLA55 hsa-miR-503 6.00
6.00 6.00 6.00 JLA57 hsa-mir-505 6.00 6.00 6.00 6.00 JLA82
hsa-mir-423* 10.39 11.13 9.84 11.00 JLA66 hsa-miR-432 6.00 6.00
6.00 6.00 JLA83 hsa-mir-425* 6.89 7.58 6.00 8.04 JLA84
hsa-mir-92-1* 6.00 6.00 6.00 6.00 JLA69 hsa-mir-193* 6.00 6.00 6.00
6.00 JLA70 hsa-miR-515-5p 6.00 6.00 6.00 6.00 JLA71 hsa-mir-516-1*
6.00 6.00 6.00 6.00 JLA85 hsa-mir-30d* 6.00 6.00 6.00 6.00 JLA125
h-miR-20b 8.95 9.35 10.04 9.35 JLA198 h-miR-191* 6.00 6.00 7.19
6.00 JLA199 h-miR-154* 6.00 6.00 6.00 6.00 EAM316 h-miR-147 6.00
6.00 6.00 6.00 EAM317 h-miR-155 8.82 7.46 6.00 8.90 EAM318
h-miR-17-3p 6.00 6.00 6.00 6.00 JLA195 h-miR-200a* 6.00 6.00 6.00
6.00 JLA196 h-miR-302a* 6.00 6.00 6.00 6.00 JLA197 h-miR-299-3p
6.00 6.00 6.00 7.60 EAM319 h-miR-182* 6.00 6.00 6.00 6.00 EAM405
h-miR-302b 6.00 6.00 6.00 6.19 EAM406 h-miR-302b* 6.00 6.00 6.00
6.00 EAM392 r-miR-352 8.00 8.07 8.34 8.37 JLA123 h-miR-423 6.00
6.00 6.00 6.00 JLA124 h-miR-18b 6.00 6.00 6.00 6.00 Data were
normalized, log2-transformed and thresholded at 6. Readings for
samples are in columns and readings for miRNAs are in rows. Due to
page limitation, every page lists only a subset of samples and
miRNAs. The data will also be available online.
Sequence CWU 1
1
798184RNAHomo sapiens 1cuccccaugg cccugucucc caacccuugu accagugcug
ggcucagacc cugguacagg 60ccugggggac agggaccugg ggac 84222RNAHomo
sapiens 2ucucccaacc cuuguaccag ug 22322RNAHomo sapiens 3cugguacagg
ccugggggac ag 22422RNAHomo sapiens 4cacugguaca aggguuggga ga
22520DNAArtificial SequenceDescription of Artificial Sequence
Synthetic primer 5cagcataggg tggagtgggt 20620DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
6tactttgcgc atcacacaga 20719DNAArtificial SequenceDescription of
Artificial Sequence Synthetic primer 7tttcctcaaa acaggaagg
19820DNAArtificial SequenceDescription of Artificial Sequence
Synthetic primer 8ccaccaagta agtcattttc 20935DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
9ccccatggcc ctgtctggga acccttgtac cagtg 351035DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
10cactggtaca agggttccca gacagggcca tgggg 351131DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
11ccctggtaca ggcctcccgg acagggacct g 311231DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
12caggtccctg tccgggaggc ctgtaccagg g 311331DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
13taactcgaga catttccaga aaagcattat g 311431DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
14atagcggccg caggtaaaat aagggcacat c 311528DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
15acttttcatg aatcccagaa gaacctat 281628DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
16ataggttctt ctgggattca tgaaaagt 281728DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
17tgaaaacttg tttcccagac tctgcatt 281828DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
18aatgcagagt ctgggaaaca agttttca 281930DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
19tgcacttctt ttttcccaga tgtgtgttgt 302030DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
20acaacacaca tctgggaaaa aagaagtgca 302130DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
21ctgttttata atttcccagt tctgcatttg 302230DNAArtificial
SequenceDescription of Artificial Sequence Synthetic primer
22caaatgcaga actgggaaat tataaaacag 302322RNAArtificial
SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 23cacugguaca aggguuggga ga 222422RNAArtificial
SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 24cucgcguaga agaguaggug ga 22256RNAArtificial
SequenceDescription of Artificial Sequence Synthetic
oligonucleotide 25aauaaa 62624DNAArtificial SequenceDescription of
Artificial Sequence Synthetic probe 26actcagaagg acaagtagag tttt
242723DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 27gtggtaatcc ctggcaatgt gat 232822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
28acactctaaa gggaaccatt tt 222921DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 29ggaaatccct ggcaatgtga t
213023DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 30aaagaagtgc accatgtttg ttt 233121DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
31aaagtgtcag atacggtgtg g 213220DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 32aagaagtgca ccgcgaatgt
203322DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 33acagttcttc aactggcagc tt 223420DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
34aacactctga agggaagcgc 203523DNAArtificial SequenceDescription of
Artificial Sequence Synthetic probe 35ctacctgcac tataagcact tta
233621DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 36cactctaaaa ggatgcactt t 213723DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
37tcagttttgc atggatttgc aca 233821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 38ttcaccaaag ggaagcactt t
213922DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 39cccaacaaca tgaaactacc ta 224022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
40acactctaaa gggaagtgcg tt 224122DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 41acaaagttct gtagtgcact ga
224220DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 42ctcccttctt tcctcccgtc 204322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
43ctagtacatc atctatactg ta 224423DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 44ctcacaccta ggttccaagg att
234522DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 45tgagctacag tgcttcatct ca 224623DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
46ttacagatgg ataccgtgca att 234721DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 47ccatctttac cagacagtgt t
214819DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 48ccacgaccga cgccacgcc 194921DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
49ctaccatagg gtaaaaccac t 215022DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 50cctctaaaag gaagcacttt ct
225121DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 51tggagacacg tgcactgtag a 215222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
52gaacatacaa agggtatcct ct 225324DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 53ttcacatagg aataaaaagc cata
245421DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 54cgaatataac acggtcgatc t 215522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
55acagctggtt gaaggggacc aa 225620DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 56cctccagccc ctccagggct
205721DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 57ggggtatttg acaaactgac a 215821DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
58tcaatcacag atagcacccc t 215922DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 59gcaaaaatgt gctagtgcca aa
226021DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 60gtagtgcaac tatgcaaaac t 216123DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
61tcatacagct agataaccaa aga 236218DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 62tggtggcagt ggtgggat
186322DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 63cttccagtcg gggatgttta ca 226422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
64acactctaaa gggatgcacg at 226522DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 65acacaaattc ggttctacag gg
226622DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 66aaagtgcttc ttacctccag at 226722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
67accctccacc atgcaaggga tg 226820DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 68acctctaaag gggagcgctt
206919DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 69cctatctccc ctctggacc 197022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
70acactctaaa gggaggcact tt 227121DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 71ggctgtcaat tcataggtca g
217222DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 72tccaggagct cacaatctag tg 227321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
73cggctgcaac acaagacacg a 217420DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 74gttaccgcag gctgctctgg
207523DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 75cagtgaattc taccagtgcc ata 237621DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
76agaaagcgct tccctgtaga g 217722DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 77tgtgagttct accattgcca aa
227821DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 78agccaagtaa tggagaacag g 217922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
79cgaaggcaac acggataacc ta 228021DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 80agaaagcgct tccctctaga g
218120DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 81tcacttttgt gactatgcaa 208221DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
82acagaaaggg cttccctttg c 218321DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 83ccaagttctg tcatgcactg a
218419DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 84tcggtccctc gggccaggg 198522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
85ggagtgaaga cacggagcca ga 228622DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 86tctaagccac catgtgaaac ca
228722DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 87acaaagttct gtgatgcact ga 228820DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
88gcaaggcagt ggcctgtaca 208923DNAArtificial SequenceDescription of
Artificial Sequence Synthetic probe 89gctgagagtg taggatgttt aca
239020DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 90tccagcaaag ggaagcgctt 209122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
91aaccgatttc agatggtgct ag 229221DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 92accctctata gggaagcgcg t
219323DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 93gtcatcatta ccaggcagta tta 239420DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
94caggtaacaa ctcgccgctc 209522DNAArtificial SequenceDescription of
Artificial Sequence Synthetic probe 95aaccaatgtg cagactactg ta
229623DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 96actgcacttt tatgaataag ctc 239722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
97gctgggtgga gaaggtggtg aa 229821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 98aacgctccaa aagaaggcac t
219921DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 99gccaatattt ctgtgctgct a 2110021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
100accagaactg agtccacagg g 2110122DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 101cgcaaggtcg gttctacggg tg
2210219DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 102tcccgtcgcc agcggaggc 1910322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
103acaccgagga gcccatcatg at 2210422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
104actgaaacca agtatgggtc gc 2210523DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
105cctgcatgac ggcctgcaag aca 2310619DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
106cagccctcct ggtggctgg 1910722DNAArtificial SequenceDescription of
Artificial Sequence Synthetic probe 107ataaggattt ttaggggcat ta
2210821DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 108atctacactg gctactgagc c 2110922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
109tattaggaac acatcgcaaa aa 2211019DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
110cgcgactgcg tcaccggcc 1911122DNAArtificial SequenceDescription of
Artificial Sequence Synthetic probe 111accagctaac aatacactgc ca
2211219DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 112cctgcgccat ctcctctac 1911322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
113atgggacatc ctacatatgc aa 2211423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
114actgtgtttc agctcagtag gca 2311522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
115ttcaaaacat gaattgctgc tg
2211622DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 116cgaacacagc agggataacc ac 2211722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
117gtacccctgg agattctgat aa 2211821DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
118actgcagaac tgttcccgct g 2111922DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 119tcacgcgagc cgaacgaaca aa
2212022DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 120agaaaatgcc cctcagtttt ga 2212122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
121acaaaagttg cctttgtgtg at 2212220DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
122agacgggagg agaggagtga 2012322DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 123acacaggacc tggagtcagg ag
2212420DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 124atcgggaggg gactgagcct 2012521DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
125cctacgttcc atagtctacc a 2112620DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 126ctcggggcag ctcagtacag
2012722DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 127gcgcatgttc tatggtcaac ca 2212820DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
128cgagccggtc gaggtccggt 2012922DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 129acagagagct tgcccttgta ta
2213022DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 130tctcgtgaca tgatgatccc cg 2213120DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
131tatgaacaat ttctaggaat 2013222DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 132agaaagcgct ttcctttgta ga
2213321DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 133ggcggacacg acattcccga t 2113422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
134cacatggcca aaacagagaa ga 2213522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
135gtctcagttt cctctgcaaa ca 2213622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
136ccacccaatg acctactcca ag 2213722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
137gctgtaaaca tccgactgaa ag 2213820DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
138tcatctcgcc cgcaaagacc 2013922DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 139atgctttttg gggtaagggc tt
2214023DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 140agaaagtgct ttcttttgga gaa 2314122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
141acggcattac cagacagtat ta 2214223DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
142gaaagtgctt ctttcctcga gaa 2314323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
143tctctgcagg ccctgtgctt tgc 2314423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
144cacaggttaa agggtctcag gga 2314520DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
145tgttgcagcg cttcatgttt 2014622DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 146acaaattcgg ttctacaggg ta
2214722DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 147agccacagtc accttctgat ct 2214823DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
148tgatagccct gtacaatgct gct 2314923DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
149catgcataca tgcacacata cat 2315023DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
150tcatagccct gtacaatgct gct 2315121DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
151caacaaacat ttaatgaggc c 2115222DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 152aactatacaa tctactacct ca
2215321DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 153tgatggacaa caaattaggt a 2115421DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
154actatgcaac ctactacctc t 2115523DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 155tatctcacag aataaacttg gta
2315621DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 156ttcagctatc acagtactgt a 2115723DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
157tcacatcagt gccattctaa ata 2315820DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
158ctatacaacc tcctacctca 2015923DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 159gtcttatgtg tgcgtgtatg tat
2316022DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 160ctcaatagac tgtgagctcc tt 2216122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
161gtgtaggtgt gtgtatgtat at 2216222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
162aacctatcct gaattacttg aa 2216323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
163cagacacacg cacatcagtc ata 2316423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
164tccatcatca aaacaaatgg agt 2316526DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
165ggacaccaag atcaatgaaa gaggca 2616622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
166aggcaaagga tgacaaaggg aa 2216721DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
167tcaccagtgc cagtccaaga a 2116823DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 168gaacaggtag tctaaacact ggg
2316923DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 169tgtgaaaagc actatactac gta 2317024DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
170atccagtcag ttcctgatgc agta 2417121DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
171agactagata tggaagggtg a 2117222DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 172gctgcaaaca tccgactgaa ag
2217320DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 173tctgggcaca cggagggaga 2017422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
174taaccgattt caaatggtgc ta 2217521DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
175acggtcaggc tttggctaga t 2117622DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 176aacaatacaa cttactacct ca
2217721DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 177agaggcaggc actcaggcag a 2117822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
178atacatactt ctttacattc ca 2217919DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
179tgggcgaccc agagggaca 1918021DNAArtificial SequenceDescription of
Artificial Sequence Synthetic probe 180gctgagtgta ggatgtttac a
2118122DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 181agaggttaag acagcagggc tg 2218222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
182atgccctttt aacattgcac tg 2218322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
183ggttcaaacc atgagtcgag ct 2218423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
184ctacgcgtat tcttaagcaa taa 2318521DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
185ggagtcgagt gatggttcaa a 2118621DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 186agaacaatgc cttactgagt a
2118722DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 187gaataatgac aggctcaccg ta 2218822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
188tcttcccatg cgctatacct ct 2218921DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
189tactatgcaa cctactactc t 2119022DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 190ccacacactt ccttacattc ca
2219122DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 191ctgaggggcc tcagaccgag ct 2219223DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
192gagggaggag agccaggaga agc 2319322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
193taactgcact agatgcacct ta 2219422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
194acaagctttt tgctcgtctt at 2219523DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
195ctacctgcac tatgagcact ttg 2319621DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
196ggccgtgact ggagactgtt a 2119722DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 197ggggacgaaa tccaagcgca gc
2219821DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 198cacagttgcc agctgagatt a 2119922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
199aataggtcaa ccgtgtatga tt 2220021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
200acatggttag atcaagcaca a 2120120DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 201gcagaagcat ttccacacac
2020222DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 202acaaccagct aagacactgc ca 2220322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
203cccctatcac gattagcatt aa 2220422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
204aggcgaagga tgacaaaggg aa 2220520DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
205acaagtgcct tcactgcagt 2020621DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 206gtctgtcaat tcataggtca t
2120722DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 207tccagcactg tccggtaaga tg 2220824DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
208atccaatcag ttcctgatgc agta 2420922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
209aaagcaagta catccacgtt ta 2221024DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
210actacctgca ctgtaagcac tttg 2421122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
211aagcggttta ccatcccaca ta 2221222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
212tatctgcact agatgcacct ta 2221321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
213tagttggcaa gtctagaacc a 2121424DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 214aacccaccga cagcaatgaa
tgtt 2421523DNAArtificial SequenceDescription of Artificial
Sequence Synthetic probe 215ctactaaaac atggaagcac tta
2321623DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 216gaacaggtag tctgaacact ggg 2321723DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
217agaaagcact tccatgttaa agt 2321823DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
218gaacagatag tctaaacact ggg 2321923DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
219ccactgaaac atggaagcac tta 2322023DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
220tcagttttgc atagatttgc aca 2322120DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
221cagcaggtac ccccatgtta 2022222DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 222ctagtggtcc taaacatttc ac
2222323DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 223acactcaaac atggaagcac tta 2322422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
224aggcatagga tgacaaaggg aa 2222521DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
225acttactgga cacctactag g 2122621DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 226cagccgctgt cacacgcaca g
2122723DNAArtificial SequenceDescription of
Artificial Sequence Synthetic probe 227aaaggcatca tataggagct gga
2322821DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 228ctgcctgtct gtgcctgctg t 2122921DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
229gccctggact aggagtcagc a 2123022DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 230cacaagttcg gatctacggg tt
2223120DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 231agaggcaggc atgcgggcag 2023224DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
232gctacctgca ctgtaagcac tttt 2423322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
233tcaccattgc taaagtgcaa tt 2223423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
234cacaaattcg gatctacagg gta 2323522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
235aaacgtggaa tttcctctat gt 2223623DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
236acaaacacca ttgtcacact cca 2323721DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
237aaagatcaac catgtattat t 2123821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 238cgcgtaccaa aagtaataat g
2123922DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 239agccacaatc accttctgat ct 2224020DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
240gccctttcat cattgcactg 2024123DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 241tctctgcagg ccgtgtgctt tgc
2324222DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 242tccctctggt caaccagtca ca 2224322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
243acggttttac cagacagtat ta 2224420DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
244gtagtgcttt ctactttatg 2024521DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 245acgtggattt tcctctatga t
2124622DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 246cccctatcac aattagcatt aa 2224722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
247ggccttctga ctccaagtcc ag 2224822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
248tgtaaaccat gatgtgctgc ta 2224922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
249aagatgtgga ccatattaca ta 2225022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
250actcaccgac aggttgaatg tt 2225122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
251ggccttctga ccctaagtcc ag 2225222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
252cacaaaccat tatgtgctgc ta 2225322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
253aaagaggtta accaggtgtg tt 2225423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
254taactgtaca aactactacc tca 2325522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
255cgaactcacc acggacaacc tc 2225623DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
256acaggccggg acaagtgcaa tat 2325721DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
257cttctttgca gatgagactg a 2125823DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 258taacccatgg aattcagttc tca
2325922DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 259tgcaaagttg ctcgggtaac ct 2226022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
260aaccatacaa cctactacct ca 2226122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
261aacatggatt ttcctctatg at 2226224DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
262aacaacaaaa tcactagtct tcca 2426322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
263gaattcatca cggccagcct ct 2226422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
264actttcggtt atctagcttt at 2226520DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
265agaggagagc cgtgtatgac 2026621DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 266acagcacaaa ctactacctc a
2126721DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 267ttgagagtgc cattatctgg g 2126822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
268aactatacaa cctactacct ca 2226923DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
269gctgccgtat atgtgatgtc act 2327022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
270aaccacacaa cctactacct ca 2227122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
271cagcatggag tcctccaggt tg 2227223DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
272ccgaccatgg ctgtagactg tta 2327323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
273tcctcatgga agggttcccc act 2327423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
274acaccaatgc cctaggggat gcg 2327521DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
275tgactgcaga gcaaaagaca c 2127621DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 276tggcattcac cgcgtgcctt a
2127722DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 277agcctatgga attcagttct ca 2227822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
278tcacaagtta gggtctcagg ga 2227922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
279aaagaagtat atgcatagga aa 2228021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
280cacaagatcg gatctacggg t 2128122DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 281ttttcccatg ccctatacct ct
2228222DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 282cgccaatatt tacgtgctgc ta 2228323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
283aagaatcttg tcccgcaggt cct 2328423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
284aacactgatt tcaaatggtg cta 2328522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
285aatgaaagcc taccatgtac aa 2228622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
286cttcagttat cacagtactg ta 2228721DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
287agacatggag gagccatcca g 2128820DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 288acaggagtct gagcatttga
2028924DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 289aagaggtttc ccgtgtatgt ttca 2429021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
290atctgcactg tcagcacttt a 2129121DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 291ggagattggc catgtaatac t
2129221DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 292gcattattac tcacggtacg a 2129321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
293acaaaccaca gtgtgctgct g 2129422DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 294agccaagctc agacggatcc ga
2229524DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 295aacccaccga caacaatgaa tgtt 2429623DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
296actgatatca gctcagtagg cac 2329723DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
297gaaagtgccc tcaaggctga gtg 2329823DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
298tccatcatta cccggcagta tta 2329922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
299gacctcagct atgacagcac tt 2230023DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
300taaacggaac cactagtgac ttg 2330123DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
301gaaaaacgcc ccctggcttg aaa 2330222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
302tcagaccgag acaagtgcaa tg 2230321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
303ccctcaaaaa ggaagcactt t 2130422DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 304ggcggaactt agccactgtg aa
2230522DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 305gaaagtgctc ccttttggag aa 2230621DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
306acaggattga gggggggccc t 2130722DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 307acactctaaa aggaggcact tt
2230822DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 308atgtatgtgg gacggtaaac ca 2230922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
309atcctctaaa aagatgcact tt 2231023DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
310gctttgacaa tactattgca ctg 2331121DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
311agaaagtact tccctctgga g 2131223DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 312tcaccaaaac atggaagcac tta
2331322DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 313acagtccaaa gggaagcact tt 2231423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
314gcttccagtc gaggatgttt aca 2331524DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
315aacagaaagt gcttccctca agag 2431620DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
316tccagtcaag gatgtttaca 2031721DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 317gcctctaaaa ggaagcactt t
2131822DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 318cagctatgcc agcatcttgc ct 2231923DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
319aaacctctaa aaggatgcac ttt 2332021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
320gcaacttagt aatgtgcaat a 2132121DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 321agaaagtgca tccctctgga g
2132222DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 322caatcagcta atgacactgc ct 2232321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
323gctctaaagg gaagcgcctt c 2132423DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 324gcaatcagct aactacactg cct
2332523DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 325agagaaagtg cttccctcta gag 2332623DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
326ctacctgcac gaacagcact ttg 2332721DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
327tcctctaaag agaagcgctt t 2132822DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 328tgctcaataa atacccgttg aa
2232923DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 329cagaaagtgc ttccctccag aga 2333022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
330agcaagccca gaccgcaaaa ag 2233122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
331cactctaaag agaagcgctt tg 2233222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
332agaaaggcag caggtcgtat ag 2233322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
333gagaaagtgc ttccctttgt ag 2233422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
334tacctgcact gttagcactt tg 2233521DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
335actccaaagg gaagcgcctt c 2133622DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 336cacataggaa tgaaaagcca ta
2233722DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 337agacagtgct tccatctaga gg 2233822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
338cctcaaggag cctcagtcta gt
2233923DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 339cagaaagggc ttccctttgt aga 2334020DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
340acaagtgccc tcactgcagt 2034123DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 341aacccaccaa agagaagcac ttt
2334223DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 342taaacggaac cactagtgac tta 2334324DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
343acactctaaa gggaagcact ttgt 2434423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
344aaaaagtgcc cccatagttt gag 2334522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
345aaccctctga aaggaagcac tt 2234623DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
346ggcacacaaa gtggaagcac ttt 2334721DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
347gctccaaagg gaagcgcttt g 2134822DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 348agagagggcc tccactttga tg
2234920DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 349aaagggcttc cctttgcaga 2035023DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
350acactcaaaa cctggcggca ctt 2335122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
351acactctaaa aggatgcacg at 2235222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
352caaaagagcc cccagtttga gt 2235323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
353ttaaacatca ctgcaagtct taa 2335422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
354acactacaaa ctctgcggca ct 2235522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
355cagaatcctt gcccaggtgc at 2235622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
356acacacaaaa gggaagcact tt 2235722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
357tctcacccag ggacaaagga tt 2235823DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
358agactcaaaa gtagtagcac ttt 2335921DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
359tagcacccag atagcaagga t 2136021DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 360catgcacatg cacacataca t
2136123DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 361ctgcagaact gttcccgctg cta 2336222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
362ggaagaacag ccctcctctg cc 2236321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
363atagagtgca gaccagggtc t 2136422DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 364gaagagagct tgcccttgca ta
2236522DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 365ataaatgaca cctccctgtg aa 2236622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
366agaggtcgac cgtgtaatgt gc 2236721DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
367tctactcaga agggtgcctt a 2136820DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 368ccagcagcac ctggggcagt
2036921DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 369ttcactccaa aaggtgcaaa a 2137023DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
370acacttactg agcacctact agg 2337123DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
371tctactccaa aaggctacaa tca 2337221DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
372actggaggaa gggcccagag g 2137323DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 373tctacccaca gacgtaccaa tca
2337422DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 374acggaagggc agagagggcc ag 2237523DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
375tgtgattgcc actctcctga gta 2337622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
376aaaaaggtta gctgggtgtg tt 2237720DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
377ctactcacag aagtgtcaat 2037821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 378ttctaggata ggcccagggg c
2137920DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 379ttcaatttct gccgcaaaag 2038023DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
380aaaggcatca tataggagct gaa 2338122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
381gctatctgct gcaacagaat tt 2238223DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
382ggctataaag taactgagac gga 2338323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
383gtgtgcttac acacttcccg tta 2338421DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
384actgaccgac cgaccgatcg a 2138521DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 385agcacgtcac ttccactaag a
2138623DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 386acagtcaggc tttggctaga tca 2338720DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
387gcaagggcga atgcagaaaa 2038821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 388gcactggact aggggtcagc a
2138920DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 389aactccgggg ctgatcaggt 2039021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
390agaggcaggc actcgggcag a 2139120DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 391cttgtaccag ttatctgcaa
2039223DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 392caatcagcta attacactgc cta 2339321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
393ttgtacgttt acatggaggt c 2139424DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 394gtgaaagtgt atgggctttg
tgaa 2439523DNAArtificial SequenceDescription of Artificial
Sequence Synthetic probe 395ctgactgact gactgactga ctg
2339622DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 396caggctcaaa gggctcctca gg 2239720DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
397ccataaagta ggaaacacta 2039821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 398aacaaaatca caagtcttcc a
2139920DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 399tcaccgacag cgttgaatgt 2040021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
400tgtaagtgct cgtaatgcag t 2140119DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 401cgggactttg agggccagt
1940219DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 402accctcatgc ccctcaagg 1940320DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
403gaatccacca cgaacaactt 2040420DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 404aaaagtaact agcacaccac
2040519DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 405agagaccggt tcactgtga 1940621DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
406acatttttcg ttattgctct t 2140719DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 407agagaccggt tcactgtga
1940822DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 408tatggcagac tgtgatttgt tg 2240920DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
409cctgattcac aacaccagct 2041021DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 410catcgttacc agacagtgtt a
2141120DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 411ggattcctgg gaaaactgga 2041222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
412tccacatgga gttgctgtta ca 2241320DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
413actggtacaa gggttgggag 2041422DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 414aacagctgct tttgggattc tg
2241520DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 415ctgggacttt gtaggccagt 2041622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
416acctaatata tcaaacatat ca 2241720DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
417agactccggt ggaatgaagg 2041823DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 418aagcccaaaa ggagaattct ttg
2341921DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 419caacatcagt ctgataagct a 2142021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
420aggaactgcc tttctctcca a 2142120DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 421gtacaatcaa cggtcgatgg
2042222DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 422acccttatca gttctccgtc ca 2242320DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
423agaattgcgt ttggacaatc 2042421DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 424tagctggttg aaggggacca a
2142519DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 425acccagcaga caatgtagc 1942622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
426cctcaaggag cttcagtcta gt 2242720DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
427acccagtagc cagatgtagc 2042821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 428ccaacaacag gaaactacct a
2142919DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 429gccctctcaa cccagcttt 1943020DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
430ccaggttcca ccccagcagg 2043120DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 431gcaatgcaac tacaatgcac
2043220DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 432acactcaaaa gatggcggca 2043320DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
433aacaaaatca ctgatgctgg 2043420DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 434acgctcaaat gtcgcagcac
2043519DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 435gagctcctgg aggacaggg 1943620DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
436acaccccaaa atcgaagcac 2043720DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 437gggtgcgatt tctgtgtgag
2043820DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 438ggaaagcgcc cccattttga 2043920DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
439actcagtaat ggtaacggtt 2044022DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 440cacttatcag gttgtattat aa
2244120DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 441gaggaaacca gcaagtgttg 2044221DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
442gtctgtcaaa tcataggtca t 2144320DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 443gcaatgcaac agcaatgcac
2044421DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 444ggggttcacc gagcaacatt c 2144521DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
445gtccgtggtt ctaccctgtg g 2144620DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 446caggccatct gtgttatatt
2044723DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 447atactagact gtgagctcct cga 2344820DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
448agtggatgtt cctctatgat 2044922DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 449ccagaaggag cacttagggc ag
2245020DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 450cgtggatttt cctctacgat 2045122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
451gctggatgca aacctgcaaa ac 2245220DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
452gagggttagt ggaccgtgtt 2045320DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 453aatcccatcc ccaggaaccc
2045420DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 454gatgtggacc atactacata 2045520DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
455cggctctgtc gtcgaggcgc 2045620DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 456ggctagtgga ccaggtgaag
2045721DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 457aaagtctcgc tctctgcccc t 2145820DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
458cagaacttag ccactgtgaa 2045922DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 459tcaacgggag tgatcgtgtc at
2246022DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 460agcctatcct ggattacttg aa 2246121DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
461agcattgcaa ccgatcccaa c 2146222DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 462ctgttcctgc tgaactgagc ca
2246322DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 463gcagcaaaca tctgactgaa ag 2246422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
464acaaattcgg ttctacaggg ta 2246523DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
465tgatagccct gtacaatgct gct 2346623DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
466tcatagccct gtacaatgct gct 2346722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
467aactatacaa tctactacct ca 2246821DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
468actatgcaac ctactacctc t 2146921DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 469ttcagctatc acagtactgt a
2147022DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 470tcgccctctc aacccagctt tt 2247120DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
471ctatacaacc tcctacctca 2047222DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 472ctcaatagac tgtgagctcc tt
2247322DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 473aacctatcct gaattacttg aa 2247423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
474tccatcatca aaacaaatgg agt 2347522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
475aggcaaagga tgacaaaggg aa 2247623DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
476gaacaggtag tctaaacact ggg 2347724DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
477atccagtcag ttcctgatgc agta 2447822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
478gctgcaaaca tccgactgaa ag 2247922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
479taaccgattt caaatggtgc ta 2248022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
480aacaatacaa cttactacct ca 2248122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
481atacatactt ctttacattc ca 2248221DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
482gctgagtgta ggatgtttac a 2148322DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 483atgccctttt aacattgcac tg
2248423DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 484tccataaagt aggaaacact aca 2348523DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
485ctacgcgtat tcttaagcaa taa 2348621DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
486agaacaatgc cttactgagt a 2148722DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 487tcttcccatg cgctatacct ct
2248822DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 488ccacacactt ccttacattc ca 2248923DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
489gagggaggag agccaggaga agc 2349022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
490acaagctttt tgctcgtctt at 2249121DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
491ggccgtgact ggagactgtt a 2149221DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 492cacagttgcc agctgagatt a
2149321DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 493acatggttag atcaagcaca a 2149422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
494acaaccagct aagacactgc ca 2249522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
495aggcgaagga tgacaaaggg aa 2249621DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
496gtctgtcaat tcataggtca t 2149724DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 497atccaatcag ttcctgatgc
agta 2449824DNAArtificial SequenceDescription of Artificial
Sequence Synthetic probe 498actacctgca ctgtaagcac tttg
2449922DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 499tatctgcact agatgcacct ta 2250023DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
500actcaccgac agcgttgaat gtt 2350124DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
501aacccaccga cagcaatgaa tgtt 2450223DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
502gaacaggtag tctgaacact ggg 2350323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
503gaacagatag tctaaacact ggg 2350423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
504tcagttttgc atagatttgc aca 2350522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
505ctagtggtcc taaacatttc ac 2250622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
506aggcatagga tgacaaaggg aa 2250722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
507cagactccgg tggaatgaag ga 2250821DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
508cagccgctgt cacacgcaca g 2150921DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 509ctgcctgtct gtgcctgctg t
2151022DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 510cacaagttcg gatctacggg tt 2251124DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
511gctacctgca ctgtaagcac tttt 2451223DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
512cacaaattcg gatctacagg gta 2351323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
513acaaacacca ttgtcacact cca 2351421DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
514cgcgtaccaa aagtaataat g 2151520DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 515gccctttcat cattgcactg
2051622DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 516tccctctggt caaccagtca ca 2251720DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
517gtagtgcttt ctactttatg 2051822DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 518cccctatcac aattagcatt aa
2251922DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 519tgtaaaccat gatgtgctgc ta 2252022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
520actcaccgac aggttgaatg tt 2252122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
521cacaaaccat tatgtgctgc ta 2252223DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
522taactgtaca aactactacc tca 2352323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
523acaggccggg acaagtgcaa tat 2352423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
524taacccatgg aattcagttc tca 2352522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
525aaccatacaa cctactacct ca 2252624DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
526aacaacaaaa tcactagtct tcca 2452722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
527actttcggtt atctagcttt at 2252821DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
528acagcacaaa ctactacctc a 2152922DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 529aactatacaa cctactacct ca
2253022DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 530aaccacacaa cctactacct ca 2253123DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
531ccgaccatgg ctgtagactg tta 2353223DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
532acaccaatgc cctaggggat gcg 2353321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
533tggcattcac cgcgtgcctt a 2153422DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 534tcacaagtta gggtctcagg ga
2253521DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 535cacaagatcg gatctacggg t 2153622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
536cgccaatatt tacgtgctgc ta 2253723DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
537aacactgatt tcaaatggtg cta 2353822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
538cttcagttat cacagtactg ta 2253920DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
539acaggagtct gagcatttga 2054021DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 540atctgcactg tcagcacttt a
2154121DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 541gcattattac tcacggtacg a 2154222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
542agccaagctc agacggatcc ga 2254323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
543actgatatca gctcagtagg cac 2354423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
544tccatcatta cccggcagta tta 2354523DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
545taaacggaac cactagtgac ttg 2354622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
546tcagaccgag acaagtgcaa tg 2254721DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
547agactagata tggaagggtg a 2154820DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 548tctgggcaca cggagggaga
2054921DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 549acggtcaggc tttggctaga t 2155022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
550tgctcaataa atacccgttg aa 2255122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
551agcaagccca gaccgcaaaa ag 2255222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
552agaaaggcag caggtcgtat ag 2255322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
553tacctgcact gttagcactt tg 2255422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
554cacataggaa tgaaaagcca ta 2255522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
555cctcaaggag cctcagtcta gt 2255620DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
556acaagtgccc tcactgcagt 2055723DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 557taaacggaac cactagtgac tta
2355823DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 558aaaaagtgcc cccatagttt gag 2355923DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
559ggcacacaaa gtggaagcac ttt 2356022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
560agagagggcc tccactttga tg 2256123DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
561acactcaaaa cctggcggca ctt
2356222DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 562caaaagagcc cccagtttga gt 2256322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
563acactacaaa ctctgcggca ct 2256422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
564acacacaaaa gggaagcact tt 2256523DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
565agactcaaaa gtagtagcac ttt 2356621DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
566catgcacatg cacacataca t 2156722DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 567ggaagaacag ccctcctctg cc
2256822DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 568gaagagagct tgcccttgca ta 2256922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
569agaggtcgac cgtgtaatgt gc 2257020DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
570ccagcagcac ctggggcagt 2057123DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 571acacttactg agcacctact agg
2357221DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 572actggaggaa gggcccagag g 2157322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
573acggaagggc agagagggcc ag 2257422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
574aaaaaggtta gctgggtgtg tt 2257521DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
575ttctaggata ggcccagggg c 2157623DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 576aaaggcatca tataggagct gaa
2357723DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 577tcaacaaaat cactgatgct gga 2357821DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
578tgagctcctg gaggacaggg a 2157923DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 579ggctataaag taactgagac gga
2358021DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 580actgaccgac cgaccgatcg a 2158124DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
581gacgggtgcg atttctgtgt gaga 2458223DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
582acagtcaggc tttggctaga tca 2358321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
583gcactggact aggggtcagc a 2158421DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 584agaggcaggc actcgggcag a
2158523DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 585caatcagcta attacactgc cta 2358624DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
586gtgaaagtgt atgggctttg tgaa 2458722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
587caggctcaaa gggctcctca gg 2258821DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
588aacaaaatca caagtcttcc a 2158921DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 589tgtaagtgct cgtaatgcag t
2159019DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 590accctcatgc ccctcaagg 1959120DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
591aaaagtaact agcacaccac 2059221DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 592acatttttcg ttattgctct t
2159322DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 593tatggcagac tgtgatttgt tg 2259421DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
594catcgttacc agacagtgtt a 2159522DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 595tccacatgga gttgctgtta ca
2259622DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 596aacagctgct tttgggattc tg 2259722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
597acctaatata tcaaacatat ca 2259823DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
598aagcccaaaa ggagaattct ttg 2359921DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
599aggaactgcc tttctctcca a 2160022DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 600acccttatca gttctccgtc ca
2260121DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 601tagctggttg aaggggacca a 2160222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
602cctcaaggag cttcagtcta gt 2260321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
603ccaacaacag gaaactacct a 2160420DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 604ccaggttcca ccccagcagg
2060520DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 605acactcaaaa gatggcggca 2060620DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
606acgctcaaat gtcgcagcac 2060720DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 607acaccccaaa atcgaagcac
2060820DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 608ggaaagcgcc cccattttga 2060922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
609cacttatcag gttgtattat aa 2261021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
610gtctgtcaaa tcataggtca t 2161121DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 611ggggttcacc gagcaacatt c
2161220DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 612caggccatct gtgttatatt 2061320DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
613agtggatgtt cctctatgat 2061420DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 614cgtggatttt cctctacgat
2061520DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 615gagggttagt ggaccgtgtt 2061620DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
616gatgtggacc atactacata 2061720DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 617ggctagtgga ccaggtgaag
2061820DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 618cagaacttag ccactgtgaa 2061922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
619agcctatcct ggattacttg aa 2262022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
620ctgttcctgc tgaactgagc ca 2262123DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
621gtggtaatcc ctggcaatgt gat 2362221DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
622ggaaatccct ggcaatgtga t 2162321DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 623aaagtgtcag atacggtgtg g
2162422DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 624acagttcttc aactggcagc tt 2262522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
625ggtacaatca acggtcgatg gt 2262622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
626tcaacatcag tctgataagc ta 2262723DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
627ctacctgcac tataagcact tta 2362823DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
628tcagttttgc atggatttgc aca 2362922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
629cccaacaaca tgaaactacc ta 2263022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
630acaaagttct gtagtgcact ga 2263124DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
631aagggattcc tgggaaaact ggac 2463222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
632ctagtacatc atctatactg ta 2263322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
633tgagctacag tgcttcatct ca 2263421DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
634agaggcaggc actcaggcag a 2163519DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 635tgggcgaccc agagggaca
1963622DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 636agaggttaag acagcagggc tg 2263722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
637tgcaatgcaa ctacaatgca cc 2263822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
638gcaaaaatgt gctagtgcca aa 2263923DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
639tcatacagct agataaccaa aga 2364022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
640cttccagtcg gggatgttta ca 2264122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
641acacaaattc ggttctacag gg 2264222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
642accctccacc atgcaaggga tg 2264321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
643ctgggacttt gtaggccagt t 2164419DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 644cctatctccc ctctggacc
1964521DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 645ggctgtcaat tcataggtca g 2164621DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
646cggctgcaac acaagacacg a 2164723DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 647cagtgaattc taccagtgcc ata
2364822DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 648tgtgagttct accattgcca aa 2264922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
649cgaaggcaac acggataacc ta 2265020DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
650tcacttttgt gactatgcaa 2065121DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 651ccaagttctg tcatgcactg a
2165223DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 652acactggtac aagggttggg aga 2365322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
653ggagtgaaga cacggagcca ga 2265422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
654acaaagttct gtgatgcact ga 2265523DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
655gctgagagtg taggatgttt aca 2365622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
656aaccgatttc agatggtgct ag 2265723DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
657gtcatcatta ccaggcagta tta 2365822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
658aaccaatgtg cagactactg ta 2265922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
659gctgggtgga gaaggtggtg aa 2266021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
660gccaatattt ctgtgctgct a 2166122DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 661cgcaaggtcg gttctacggg tg
2266222DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 662acaccgagga gcccatcatg at 2266323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
663cctgcatgac ggcctgcaag aca 2366422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
664ataaggattt ttaggggcat ta 2266522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
665tattaggaac acatcgcaaa aa 2266622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
666accagctaac aatacactgc ca 2266722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
667atgggacatc ctacatatgc aa 2266822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
668ttcaaaacat gaattgctgc tg 2266922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
669gtacccctgg agattctgat aa 2267022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
670tcacgcgagc cgaacgaaca aa 2267122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
671acaaaagttg cctttgtgtg at 2267222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
672acacaggacc tggagtcagg ag 2267321DNAArtificial
SequenceDescription of Artificial Sequence Synthetic
probe 673cctacgttcc atagtctacc a 2167422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
674gcgcatgttc tatggtcaac ca 2267522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
675acagagagct tgcccttgta ta 2267622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
676cgaatccacc acgaacaact tc 2267720DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
677tatgaacaat ttctaggaat 2067821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 678ggcggacacg acattcccga t
2167922DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 679gtctcagttt cctctgcaaa ca 2268022DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
680gctgtaaaca tccgactgaa ag 2268122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
681atgctttttg gggtaagggc tt 2268222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
682acggcattac cagacagtat ta 2268323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
683tctctgcagg ccctgtgctt tgc 2368420DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
684tgttgcagcg cttcatgttt 2068522DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 685agccacagtc accttctgat ct
2268623DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 686aaactcagta atggtaacgg ttt 2368721DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
687caacaaacat ttaatgaggc c 2168821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 688tgatggacaa caaattaggt a
2168923DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 689tatctcacag aataaacttg gta 2369023DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
690tcacatcagt gccattctaa ata 2369123DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
691gtcttatgtg tgcgtgtatg tat 2369222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
692gtgtaggtgt gtgtatgtat at 2269323DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
693cagacacacg cacatcagtc ata 2369426DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
694ggacaccaag atcaatgaaa gaggca 2669521DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
695tcaccagtgc cagtccaaga a 2169623DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 696tgtgaaaagc actatactac gta
2369722DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 697ggcggaactt agccactgtg aa 2269821DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
698acaggattga gggggggccc t 2169922DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 699atgtatgtgg gacggtaaac ca
2270023DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 700gctttgacaa tactattgca ctg 2370123DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
701tcaccaaaac atggaagcac tta 2370223DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
702gcttccagtc gaggatgttt aca 2370320DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
703tccagtcaag gatgtttaca 2070422DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 704cagctatgcc agcatcttgc ct
2270521DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 705gcaacttagt aatgtgcaat a 2170622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
706caatcagcta atgacactgc ct 2270723DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
707gcaatcagct aactacactg cct 2370823DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
708ctacctgcac gaacagcact ttg 2370921DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
709ccatctttac cagacagtgt t 2171021DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 710ctaccatagg gtaaaaccac t
2171121DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 711tggagacacg tgcactgtag a 2171221DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
712cctgattcac aacaccagct g 2171324DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 713ttcacatagg aataaaaagc
cata 2471422DNAArtificial SequenceDescription of Artificial
Sequence Synthetic probe 714acagctggtt gaaggggacc aa
2271522DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 715gaaagagacc ggttcactgt ga 2271622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
716aaaagagacc ggttcactgt ga 2271721DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
717agaattgcgt ttggacaatc a 2171823DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 718gaaacccagc agacaatgta gct
2371924DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 719gagacccagt agccagatgt agct 2472021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
720ggggtatttg acaaactgac a 2172122DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 721ggttcaaacc atgagtcgag ct
2272221DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 722ggagtcgagt gatggttcaa a 2172322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
723gaataatgac aggctcaccg ta 2272422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
724acactctaaa gggaaccatt tt 2272523DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
725aaagaagtgc accatgtttg ttt 2372623DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
726catgcataca tgcacacata cat 2372720DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
727aacactctga agggaagcgc 2072821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 728cactctaaaa ggatgcactt t
2172921DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 729ttcaccaaag ggaagcactt t 2173021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
730gtccgtggtt ctaccctgtg g 2173122DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 731acactctaaa gggaagtgcg tt
2273223DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 732ctcacaccta ggttccaagg att 2373322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
733ccagaaggag cacttagggc ag 2273423DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
734ttacagatgg ataccgtgca att 2373522DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
735gctggatgca aacctgcaaa ac 2273622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
736cctctaaaag gaagcacttt ct 2273720DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
737aatcccatcc ccaggaaccc 2073821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 738cgaatataac acggtcgatc t
2173920DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 739cggctctgtc gtcgaggcgc 2074021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
740tcaatcacag atagcacccc t 2174121DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 741gtagtgcaac tatgcaaaac t
2174222DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 742acactctaaa gggatgcacg at 2274322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
743aaagtgcttc ttacctccag at 2274420DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
744acctctaaag gggagcgctt 2074522DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 745acactctaaa gggaggcact tt
2274623DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 746atactagact gtgagctcct cga 2374722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
747tccaggagct cacaatctag tg 2274821DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
748agaaagcgct tccctgtaga g 2174921DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 749agccaagtaa tggagaacag g
2175021DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 750agaaagcgct tccctctaga g 2175121DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
751acagaaaggg cttccctttg c 2175222DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 752tctaagccac catgtgaaac ca
2275320DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 753gcaaggcagt ggcctgtaca 2075420DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
754tccagcaaag ggaagcgctt 2075521DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 755accctctata gggaagcgcg t
2175621DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 756aacgctccaa aagaaggcac t 2175721DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
757accagaactg agtccacagg g 2175821DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 758atctacactg gctactgagc c
2175923DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 759actgtgtttc agctcagtag gca 2376021DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
760actgcagaac tgttcccgct g 2176122DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 761agaggaaacc agcaagtgtt ga
2276221DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 762aaagtctcgc tctctgcccc t 2176322DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
763ccacccaatg acctactcca ag 2276422DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
764tcaacgggag tgatcgtgtc at 2276521DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
765agcattgcaa ccgatcccaa c 2176620DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 766tcatctcgcc cgcaaagacc
2076723DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 767agaaagtgct ttcttttgga gaa 2376823DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
768gaaagtgctt ctttcctcga gaa 2376922DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
769gcagcaaaca tctgactgaa ag 2277023DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
770ctacctgcac tatgagcact ttg 2377122DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
771ggggacgaaa tccaagcgca gc 2277222DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
772aataggtcaa ccgtgtatga tt 2277320DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
773gcagaagcat ttccacacac 2077422DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 774cccctatcac gattagcatt aa
2277520DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 775acaagtgcct tcactgcagt 2077622DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
776tccagcactg tccggtaaga tg 2277722DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
777aaagcaagta catccacgtt ta 2277822DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
778aagcggttta ccatcccaca ta 2277921DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
779tagttggcaa gtctagaacc a 2178023DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 780ctactaaaac atggaagcac tta
2378123DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 781agaaagcact tccatgttaa agt 2378221DNAArtificial
SequenceDescription of Artificial Sequence Synthetic probe
782tactatgcaa cctactactc t 2178322DNAArtificial SequenceDescription
of Artificial Sequence Synthetic probe 783ctgaggggcc tcagaccgag ct
2278422DNAArtificial SequenceDescription of Artificial Sequence
Synthetic probe 784taactgcact agatgcacct ta
227851191DNAHomo sapiens 785gacatttcca gaaaagcatt atggttttca
gaacacttca agttgacttg ggatatatca 60ttcctcaaca tgaaactttt catgaatggg
agaagaacct atttttgttg tggtacaaca 120gttgagagca gcaccaagtg
catttagttg aatgaagtct tcttggattt cacccaacta 180aaaggatttt
taaaaataaa taacagtctt acctaaatta ttaggtaatg aattgtagcc
240agttgttaat atcttaatgc agattttttt aaaaaaaaca taaaatgatt
tatctgtatt 300ttaaaggatc caacagatca gtattttttc ctgtgatggg
ttttttgaaa tttgacacat 360taaaaggtac tccagtattt cacttttctc
gatcactaaa catatgcata tatttttaaa 420aatcagtaaa agcattactc
taagtgtaga cttaatacca tgtgacattt aatccagatt 480gtaaatgctc
atttatggtt aatgacattg aaggtacatt tattgtacca aaccatttta
540tgagttttct gttagcttgc tttaaaaatt attactgtaa gaaatagttt
tataaaaaat 600tatattttta ttcagtaatt taattttgta aatgccaaat
gaaaaacgtt ttttgctgct 660atggtcttag cctgtagaca tgctgctagt
atcagagggg cagtagagct tggacagaaa 720gaaaagaaac ttggtgttag
gtaattgact atgcactagt atttcagact ttttaatttt 780atatatatat
acattttttt tccttctgca atacatttga aaacttgttt gggagactct
840gcatttttta ttgtggtttt tttgttattg ttggtttata caagcatgcg
ttgcacttct 900tttttgggag atgtgtgttg ttgatgttct atgttttgtt
ttgagtgtag cctgactgtt 960ttataatttg ggagttctgc atttgatccg
catcccctgt ggtttctaag tgtatggtct 1020cagaactgtt gcatggatcc
tgtgtttgca actggggaga cagaaactgt ggttgatagc 1080cagtcactgc
cttaagaaca tttgatgcaa gatggccagc actgaacttt tgagatatga
1140cggtgtactt actgccttgt agcaaaataa agatgtgccc ttattttacc t
119178622RNAHomo sapiens 786ucucccaacc cuuguaccag ug 2278722RNAMus
sp. 787ucucccaacc cuuguaccag ug 2278822RNARattus sp. 788ucucccaacc
cuuguaccag ug 2278923RNABos sp. 789ucucccaacc cuuguaccag ugu
2379022RNAUnknownDescription of Unknown Unknown frog sequence
790ucucccaacc cuuguaccag ag 2279122RNADanio rerio 791ucucccaauc
cuuguaccag ug 2279252DNAHomo sapiens 792atgaatggga gaagaattgt
ttgggagact tttgggagat taatttggga gt 5279356DNAMus sp. 793atggctgaga
gaagagttat ttgggagaat ttttgggaga tccgtttggg cgtttt 5679458DNARattus
sp. 794gtgactgagg ggagatttat ttgggagaat ttctttggga gattccgttt
gggcactt 5879552DNACanis familiaris 795atgaatggga gaagagttgt
ttgggagatt tttgggagat taattcagag gt 5279653DNADidelphis virginiana
796atgaatggga gatggatttt tcttgcagat ttttgggaga ttaatccaaa ttt
5379755DNAGallus sp. 797gtgaatggga gacgagtgtt cctgggagat ttttgggaga
acataccttg ggtct 5579850DNAXenopus tropicalis 798atgattggga
gatgatgtgg gagattggtc tgtatgataa acccaagaac 50
* * * * *