U.S. patent application number 09/727931 was filed with the patent office on 2001-12-06 for method of newborn indentification and tracking.
This patent application is currently assigned to Identigene, Inc.. Invention is credited to Caskey, Caroline, Staub, Rick W..
Application Number | 20010048756 09/727931 |
Document ID | / |
Family ID | 22696169 |
Filed Date | 2001-12-06 |
United States Patent
Application |
20010048756 |
Kind Code |
A1 |
Staub, Rick W. ; et
al. |
December 6, 2001 |
Method of newborn indentification and tracking
Abstract
A method of ensuring that each newborn infant is identified at
birth and maintaining the correct newborn and mother pairing at
least until discharge of the mother and child. The method involves
genotyping the infant and/or birth mother at one or more times.
Inventors: |
Staub, Rick W.; (Sugar Land,
TX) ; Caskey, Caroline; (Houston, TX) |
Correspondence
Address: |
Tamsen Valoir, Ph.D.
Jenkens & Gilchrist
A Professional Corporation
1100 Louisiana, Ste. 1800
Houston
TX
77002-5214
US
|
Assignee: |
Identigene, Inc.
|
Family ID: |
22696169 |
Appl. No.: |
09/727931 |
Filed: |
November 30, 2000 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09727931 |
Nov 30, 2000 |
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09189156 |
Nov 9, 1998 |
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6187540 |
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Current U.S.
Class: |
382/129 ;
382/134 |
Current CPC
Class: |
C12Q 1/6806 20130101;
C12Q 2600/156 20130101; C12Q 1/6888 20130101 |
Class at
Publication: |
382/129 ;
382/134 |
International
Class: |
G06K 009/00 |
Claims
What is claimed is:
1. A method for ensuring that a newborn/mother pairing is correct
at discharge, said method comprising: a. obtaining a first sample
of newborn cells at the birth of a newborn; b. storing said first
sample on a tamper-proof collection device; c. forwarding said
tamper-proof collection device to a genotyping location; and d.
examining said tamper-proof collection device to ensure that
tampering has not occurred. e. genotyping said first sample to
provide a first newborn fingerprint; f. obtaining a second sample
of newborn cells from said newborn prior to discharge in accordance
with steps b, c and d; g. genotyping said second sample to provide
a second newborn fingerprint; and h. comparing said first and
second newborn fingerprints, wherein substantial identity of the
first and second newborn fingerprints indicates that said newborn
has not been switched prior to discharge.
2. The method of claim 1, further comprising the step of storing
said tamper-proof collection device for possible future use.
3. A method as in claim 1, wherein said sample of newborn cells is
obtained from a buccal swab, blood, cord blood, amniotic fluid,
embryonic tissue, hair, skin, or fingernail clipping.
4. A method as in claim 1, further comprising the steps of: a.
obtaining at least one sample of maternal cells from a mother in
accordance with steps b, c and d of claim 1; b. genotyping said
sample of maternal cells to provide a maternal fingerprint; and c.
comparing said maternal fingerprint and said first or second
newborn fingerprints, wherein about 50% identity between the
maternal fingerprint and the first or second newborn fingerprints
indicates that the newborn/mother pairing is correct.
5. The method of claim 1, further comprising the step of generating
a report comprising a summary of said comparison.
6. The method of claim 4, further comprising the step of generating
a report comprising a summary of said comparisons.
7. A method for ensuring that a newborn and a mother are related at
discharge, said method comprising: a. obtaining discharge-samples
of newborn cells from a newborn and maternal cells from a mother
prior to discharge; b. genotyping said discharge-samples to provide
a discharge newborn fingerprint and a discharge maternal
fingerprint; c. comparing said discharge newborn fingerprint and
said discharge maternal fingerprint, wherein about 50% identity
indicates that said newborn and said mother are related.
8. The method of claim 7, comprising the further step of: a.
obtaining a birth-sample of newborn and maternal cells at the birth
of said newborn; b. genotyping said birth-samples to provide a
birth newborn fingerprint and a birth maternal fingerprint; c.
comparing said birth newborn fingerprint, said discharge newborn
fingerprint, said birth maternal fingerprint, and said discharge
maternal fingerprint, wherein substantial identity between the
birth newborn fingerprint and discharge newborn fingerprint and
substantial identity between the birth maternal fingerprint and
discharge maternal fingerprint confirm that the samples have not
been tampered with; and wherein 50% identity between the newborn
fingerprints and the maternal fingerprints confirm that the newborn
and mother are related.
9. The method of claim 7, further comprising the following steps:
a. storing said discharge-samples on a single tamper-proof
collection device; b. forwarding said tamper-proof collection
device to a genotyping location; c. examining said tamper-proof
collection device to ensure that tampering has not occurred.
10. The method of claim 8, further comprising the following steps:
a. storing said discharge-samples and said birth-samples on two or
fewer tamper-proof collection devices; b. forwarding said
tamper-proof collection devices to a genotyping location; c.
examining said tamper-proof collection devices to ensure that
tampering has not occurred.
11. The method of claim 9, further comprising the step of retaining
said tamper-proof collection device for future use.
12. The method of claim 10, further comprising the step of
retaining said tamper-proof collection devices for future use.
13. The method of claim 7, wherein said sample of newborn cells is
obtained from a buccal swab, blood, cord blood, amniotic fluid,
embryonic tissue, hair, skin or fingernail clipping and wherein
said sample of maternal cells is obtained from blood, buccal swab,
hair or fingernail clippings.
14. The method of claim 8, wherein said sample of newborn cells is
obtained from a buccal swab, blood, cord blood, amniotic fluid,
embryonic tissue, hair, skin or fingernail clipping and wherein
said sample of maternal cells is obtained from blood, buccal swab,
hair or fingernail clippings.
15. The method of claim 7, wherein said sample of newborn cells and
maternal cells are obtained from a buccal swab.
16. The method of claim 8, wherein said sample of newborn cells and
maternal cells are obtained from a buccal swab.
17. The method of claim 7, wherein said discharge-samples of
newborn cells and maternal cells are selected from the group
consisting of separate samples, mixed samples, or separate samples
and a mixed sample.
18. The method of claim 8, wherein said discharge-samples of
newborn cells and maternal cells are selected from the group
consisting of separate samples, mixed samples, or separate samples
and a mixed sample.
19. The method of claim 7, further comprising the step of
generating a report comprising a summary of said comparison.
20. The method of claim 8, further comprising the step of
generating a report comprising a summary of said comparisons.
21. An improved sample collection device for use in identifying
newborn/mother pairs, said device comprising: i. a location and
label for a maternal cell sample, ii. a location and label for a
newborn cell sample; iii. optionally, a location and label for a
mixed newborn and mother cell sample; and iv. optionally, a
location and label for a paternal cell sample.
22. The sample collection device of claim 4, wherein the device is
selected from the group consisting of a Guthrie card, a trifold
collection card, a bifold collection card, paper, slide, tube or
container.
Description
1. SUMMARY OF THE INVENTION
[0001] The present invention relates to a method of uniquely
identifying a newborn and mother pair at the birth of a child in a
hospital-like setting and ensuring that the newborn/mother pairing
has been correctly maintained at least until discharge of the
mother and child pair. The invention also provides a unique sample
collection means that prevents samples from being mislabeled or
incorrectly associated with a non-family member and can be
permanently stored for future identification purposes.
2. DESCRIPTION OF THE BACKGROUND
[0002] Identification of infants at birth is a critical issue for
hospitals, birthing centers and other institutions where multiple
births occur. With approximately 300,000 infants born worldwide
each day, a large hospital may experience over one hundred new
births each day. A large hospital may see as many as a hundred new
infants each day. Correct identification of infants is essential to
ensure that each mother travels home with her own child.
[0003] In the past infants have been identified by means of
footprints. However, this is not a satisfactory method of
identifying infants because there is no means of ensuring that a
footprint is associated with a particular mother, other than
placing a footprint in the mother's hospital records. Further,
footprints of newborn infants are difficult to take and difficult
to distinguish. Additionally, the footprints are useful for only a
short period in identifying the infant and will not suffice as a
permanent identification means.
[0004] Current identification technologies generally consist of
attaching an identification device to the newborn with a matching
device for the mother. Before an infant can be moved from the
hospital, the devices are compared to ensure that only the mother
of that infant can leave with the child. Such devices include the
typical wrist bands or bracelets, which today are often
electronically readable (see e.g., WO98/18111). In another
variation, the mother wears a wrist band, but the infant has an
umbilical clamp (see e.g., U.S. Pat. Nos. 5,484,060 and 5,608,382)
and in yet another variation, the infant is actually marked with a
semi-permanent ink (see e.g., GB2,273,266 and U.S. Pat. No.
5,484,060).
[0005] However, any device or external labeling means can be
intentionally defeated, by changing the markings or electronic
signature on the existing device, or by completely replacing the
device with an appropriately marked device. Recently, it was
discovered in the United States that two infants were switched at
birth. Evidence strongly suggested that the switching was not
accidental. Tragically, the switch was not discovered for several
years and might not ever have been discovered absent a paternity
contest involving one of the children. In its aftermath, the event
leaves considerable consternation about how to cope with child
custody issues, visitation rights, hospital liability, and an
ongoing criminal investigation.
[0006] Public concern over this issue is significant. A recent
market survey created by an academic institution was conducted on
200 expectant mothers to assess their interest in a service that
would assure them that their infants had not been switched at
birth. An overwhelming 85% of the respondents wanted such a service
and would be willing to pay for it. Public concern has also reached
the U.S. Congress. Proposed legislation entitled "The Infant
Protection and Baby Switching Prevention Act of 1998" (H.R. 4680)
has been introduced into the House of Representatives in an effort
to require hospitals to address this problem. Unfortunately, no
specific solution was recommended in the Act.
[0007] Therefore, although rare, infant switches do occur and with
potentially devastating consequences. A failsafe method of uniquely
identifying which infant belongs to which mother is urgently
required. Such system should be tamper-proof, simple, easy, and
cost effective. Furthermore, the ideal system would create a
permanent record allowing for future identification of the child in
the event of abduction or accident.
[0008] Genotyping has been used to identify paternity, and
occasionally maternity, where contested, usually in a child support
context. Genotyping has also been suggested and used after the fact
where it is suspected that infants have been switched. See e.g., de
Pancorbo M. M., et al., Newborn Identification: A Protocol Using
Microsatellite DNA as an alternative to Footprinting, Clin. Chim.
Acta (1997) 263(1): 33-42. However, to date no one has applied
genotyping technology to systematically identify infants at birth
and again at discharge to ensure that no switching has occurred and
that the infant has been correctly paired with its birth mother.
Furthermore, no one has provided a permanent storage mechanism for
future identification purposes.
[0009] Such massive genotyping efforts have never been applied in a
hospital setting and present significant logistical concerns. It
would not suffice, for example, for a sample to be merely collected
and later typed within the hospital environment because such a
process is subject to the same labeling errors that currently exist
with neonatal samples such as cord blood samples. See e.g.,
Heckman, Maria, et al., Quality Improvement Principles in Practice:
The Reduction of Umbilical Cord-Blood Errors in the Labor and
Delivery. Suite; Interdisciplinary Performance Improvement, J.
Nursing Care Quality (1998) 3(12): 47 (noting that in the eight
months prior to their process improvement efforts there were 18
mislabeled specimens out of 3,504 births--an error rate of
0.5%).
SUMMARY OF THE INVENTION
[0010] The only failsafe method of identifying correct
infant/mother pairing is by genetic typing of the infant and/or the
putative mother. However, prior to the present invention, no one
has routinely employed genotyping for this purpose or devised a
simple, inexpensive system that can be routinely performed at birth
and/or at discharge. The method of the present invention has the
benefit that even if the hospital records are incorrect or have
been intentionally altered, such an event will be indicated and an
infant/mother pairing can still be correctly determined.
[0011] In one embodiment, the invention is a method for ensuring
that a newborn/mother pairing is correct at discharge. The method
comprises obtaining a first sample of newborn cells at the birth of
a newborn. The sample is stored on a tamper-proof collection
device, forwarding to a genotyping ocation, and examined to ensure
that tampering has not occurred. The first sample is genotyped to
provide a first newborn fingerprint. Likewise, a second sample of
newborn cells is obtained and treated as the first sample. The
first and second newborn fingerprints are compared, and substantial
identity of the two fingerprints indicates that said newborn has
not been switched prior to discharge.
[0012] The tamper-proof collection device may also be stored in a
dry, dark location for possible future use. Sample of newborn cells
may be obtained from a buccal swab, blood, cord blood, amniotic
fluid, embryonic tissue, hair, or fingernail clipping. Cells may be
collected at birth or prior thereto.
[0013] In an additional embodiment, at least one sample of maternal
cells from a mother is collected as above. It is genotyped to
provide a maternal fingerprint, and comparison of the maternal
fingerprint and said first or second newborn fingerprints indicates
maternity where there is evidence for transmittance of an allele
from the mother to the infant at all marker loci studied (defined
herein as "about 50% identity"). This result confirms that the
newborn/mother pairing is correct.
[0014] In all cases, a report summarizing the results of the
genotyping comparison can be generated and forwarded to the parents
or hospital.
[0015] In another embodiment, the method comprises obtaining
discharge-samples of newborn cells from a newborn and maternal
cells from a mother prior to discharge, genotyping said
discharge-samples to provide a discharge newborn fingerprint and a
discharge maternal fingerprint and comparing the discharge newborn
and maternal fingerprints. As above, where there is about 50%
identity the newborn and mother are related, thus confirming that
the newborn/mother pairing is correct.
[0016] The method can be modified by also obtaining a birth-sample
of newborn and maternal cells at the birth of said newborn;
genotyping said birth-samples to provide a birth newborn
fingerprint and a birth maternal fingerprint; and comparing all
four fingerprints. Substantial identity between the two newborn
fingerprints and substantial identity between the two maternal
fingerprints confirms that the samples have not been tampered with.
-About 50% identity between the newborn and the maternal
fingerprints confirm that the newborn and mother are related.
[0017] Samples may be handled as above and/or stored for future
use. The sample of newborn cells can be obtained from a buccal
swab, blood, cord blood, amniotic fluid, embryonic tissue, hair, or
fingernail clipping, and the like and the sample of maternal cells
can be obtained from blood, buccal swab, hair, skin or fingernail
clippings, etc. In a preferred embodiment, buccal cells are used.
Furthermore, the samples may be separate samples, mixed samples, or
separate samples and a mixed sample. Reports can be generated as
above.
[0018] The invention also pertains to an improved sample collection
device, the improvement comprising a location and label for a
maternal cell sample, a location and label for a newborn cell
sample and optionally, a location and label for a mixed
newborn/mother cell sample or a paternal sample.
DETAILED DESCRIPTION OF THE INVENTION
[0019] About 50% Identity
[0020] Because a child inherits about half its DNA from its mother,
an infant and mother should have about half identity in genotype,
allowing however, for rare non-mendelian events and an acceptable
rate of error in data collection (for example, where gel migration
varies slightly due to temperature and other factors). Thus, about
50% identity in genotype between the infant and a putative mother
indicates that the infant has inherited one allele (of two) at each
marker from the putative mother and the mother and infant are
related.
[0021] Birth-sample
[0022] As used herein, the term "birth-sample" refers to a sample
that is collected at birth, during, or prior thereto.
[0023] Birth Fingerprint
[0024] As used herein the term "birth newborn fingerprint" or
"birth maternal fingerprint" refers to a DNA genotype that is
ascertained from a birth-sample. Likewise a "discharge fingerprint"
refers to genotypes determined from a discharge-sample.
[0025] Collection Device
[0026] Any device that can be used to collect and store samples,
including Guthrie cards, tubes, swabs, papers, slides, containers
and the like. Such devices can be made tamper-proof with the
inclusion of seals and the like. In a preferred embodiment,
collection devices are modified to allow for the collection and
labeling of multiple samples.
[0027] Discharge-sample
[0028] As used herein the phrase refers to a sample that is
collected shortly before or during the discharge process.
[0029] Genetic Typing
[0030] Also genotyping, fmgerprinting, DNA typing, or any similar
phase. The term includes the use of any means known to those
skilled in the art for determining an individual's genotype. For
example, techniques can be nucleic acid based including size
fractionation, allele specific oligonucleotide (ASO) hybridization,
sequencing, restriction fragment length polymorphism (RFLP)
analysis, denaturation temperature analysis, mass spectrometry
analysis, etc. The methodologies are numerous, continually
developing, and cannot be detailed herein. The reader is referred
to the references cited herein for details.
[0031] Marker
[0032] Also polymorphism. Any sequence in the genome that is known
to vary between individuals. For example, the IL-1RN gene has a
marker that consists of a variable number of tandem repeats (VNTR).
To date, this marker is thought to have five alleles. A single base
polymorphism is also called an "SNP"--single nucleotide
polymorphism. There are a variety of marker types, including VNTRs,
simple tandem repeats (STRs), complex tandem repeats (CTRs), SNPs,
microsatellites, etc.
[0033] Newborn/Mother Pair
[0034] Also infant/mother pair or any similar phrase. Refers to a
mother and her own newborn infant.
[0035] Newborn/Mother Pairing
[0036] Refers to the assignment of a mother and infant to each
other.
[0037] Newborn Fingerprint
[0038] A unique genetic fingerprint or genotype corresponding to a
newborn.
[0039] PCR--Polymerase chain reaction. A method of amplifying small
amounts of DNA for ease of analysis. Many variations of the basic
amplification protocol are well known to those of skill in the
art.
[0040] Substantial Identity
[0041] As used herein, the term means that samples show the same
genotypes, but nonetheless accommodates an acceptable rate of error
in data collection.
[0042] Generally speaking, the invention is directed to methods and
devices associated with same for the failsafe identification of
infants to ensure that the correct infant is sent home with a given
mother. The invention involves genotyping the infant, and/or the
mother, one or more times to ascertain that no switching has
occurred.
[0043] In its simplest embodiment, only the newborn's cells are
sampled at birth. The sample is collected onto a tamper-proof card
and placed into a lock box for routine transfer to an independent
laboratory for subsequent testing. The sample is labeled with both
mother and newborn names and preferably is initialed by a hospital
witness to ensure that the sample on the card was collected from
the newborn at birth. A similar sample is collected at discharge
and both samples are sent to an independent laboratory for
analysis. In this system, it is important that the sample cards are
rendered tamper-proof to ensure that samples have not been
compromised.
[0044] In the independent test laboratory, all samples from a given
institution are typed and for each pair of birth/discharge samples,
a report is produced that can be provided to the parents which
assures them that the infant birthed is the same child the parent
brought home. If there is some discrepancy in the two samples, it
may be possible to compare against all of the samples from a given
institution and/or obtain additional maternal samples to ensure
correct pairing. Thus, this system provides an important, yet cost
effective back-up means of accurately identifying infants.
[0045] This embodiment is particularly preferred where simple and
fast genotyping technologies have not yet been established in a
given hospital. In this way, the hospital gains the assurance that
only a genotype can provide without having to implement a new
series of process steps. However, this embodiment, although the
simplest, is still subject to errors created by intentional
mislabeling of samples. Thus, this embodiment is best suited as a
backup system for the existing bracelet or cord clamp systems and
not a replacement system. As indicated above, some 85% of expectant
parents indicated they would be willing to pay for such a service
and this simple embodiment is both cost effective and minimally
intrusive. However, even in this embodiment, it may be preferred
that both maternal and newborn cells are sampled in order to ensure
that effects of intentional labeling errors are minimized, as
described herein.
[0046] In a second embodiment, newborn and maternal samples are
collected prior to discharge, and as above, may be sent off-site
for analysis. Both samples are collected onto a single card, thus
minimizing the effects of mislabeling errors. This methodology
ensures that the correct newborn/mother pairing occurred at
discharge. As above, a report can be generated and sent to the
anxious parent.
[0047] These embodiments are simple embodiments and are cost
effective with current technology. However, because there is the
possibility of intentional mislabeling of samples, they are not
appropriate as a system to replace existing infant identification
means, but function rather as a safeguard to ensure that the
existing methodology has not been tampered with. In order to use
genotyping as a method in replacement of the existing bracelet/cord
clamp identification technologies, it is felt that additional
redundancies are required.
[0048] Therefore, a more sophisticated embodiment, cells of both
the mother and the child are sampled and typed to create a unique
newborn/mother genetic fingerprint. This unique newborn/mother
fingerprint can be electronically coded into the existing bracelet
or cord clamp devices and/or merely stored under normal record
keeping procedures. Prior to discharge of the pair, additional cell
samples can be collected and retyped to ensure that the correct
pairing has been maintained and that the child has not been
switched with another. Variations between the initial and
subsequent newborn/mother fingerprints indicate that switching, an
error in data analysis, or an error in recordation may have
occurred and suggest additional data analysis. If necessary, a more
detailed genome analysis of the putative mother and child will
conclusively establish correct pairing.
[0049] This particular embodiment of the invention is technically
feasible with current technology, but is not yet cost effective for
routine screening. However, with the rapid development of existing
genetic analysis technologies, it will soon be feasible to have an
automated machine on site in every hospital which can rapidly take
and confirm genotypes.
[0050] In another embodiment, the method comprises of three types
of DNA samples; a maternal sample; a newborn sample and a mixed
sample. The mixed sample acts as an internal control to ensure that
the maternal and newborn samples have been correctly assigned to
each other upon typing. However; a single mixed sample or only the
separate maternal and newborn samples may also be employed. Mixed
DNA samples are readily obtainable form a variety of sources,
including blood, cord blood, amniotic fluid or any other tissue
which has a mixture of both fetal and maternal cells or genetic
material. Alternatively, separate samples of each may be manually
mixed. Of course, it is also possible to add paternal samples to
the collection cards as well. However, because of the potential
sensitivity of paternity, this may not be appropriate for routine
use, but can be provided on request.
[0051] The taking of samples at birth need not await complete
delivery of the newborn. In fact, the genotyping analysis can begin
prior to birth by sampling the amniotic fluid, or other
maternal/embryonic tissues. This may even be preferred as the
genotyping process itself can reasonably be expected to require at
least an hour, even with the most sophisticated of current
technologies. Thus, the taking of samples "at birth" expressly
contemplates and includes fetal sampling. One particularly useful
means of establishing a mother/child fingerprint is with the use of
fetal cell sorting to separate the fetal cells that are found in
the maternal bloodstream. With this technology, the pair can be
safely typed before delivery without risk to the fetus. This
procedure helps to eliminate the necessity of additional tests
during delivery, at a time when the minimization of extraneous
activities is desirable.
[0052] All samples may be stored for future use. One easy reliable
means of storing blood, for example, is on the Guthrie card
generally used for newborn screening of inborn errors of
metabolism. Whole blood is collected on filter paper, dried and
stored at room temperature. The use of a single card, specially
designed for collecting infant and mother blood samples will ensure
that the samples are always associated and cannot be separated.
Alternatively, blood samples may be mixed and contained in a single
collection device or tube.
[0053] A Guthrie-like card that contains separate sample collection
spaces and labeling indicia so that maternal and newborn samples
may be collected on the same card has been designed. If desired, a
space can be included for paternal samples as well. The use of a
single card for the collection of samples ensures that samples
cannot be inadvertently associated with a non-family member and
helps to eliminate at least one source of error.
[0054] The multiple-use card especially helps to eliminate errors
in those institutions where an infant record is not created until
after the birth of the infant. Thus, upon sample collection there
is a period of awaiting a hospital record number before a given
sample can be correctly labeled and this is an important source of
mislabeling errors in the process. In those hospitals where an
infant record is created at the time of admitting the expectant
mother, this is not an issue and the sample can be correctly
labeled at the onset.
[0055] It is strongly suggested that preprinted maternal and
newborn labels, coded to show the relationship, be created on
admittance of the expectant mother and used throughout the hospital
stay. This additional level of automation will ensure that the
sample collection card is correctly labeled. However, even in the
event of labeling errors in those hospitals that lack such process
measures, the presence of both samples on a single card is an
improvement over separate samples because in the event of complete
labeling or record failure, the samples on the cards can still be
typed and infants matched to mothers on the basis of genotype.
Further, the inclusion of a mixed sample provides an important
internal positive control.
[0056] Another preferred sample type is that obtained by a buccal
swab. This may be preferred for pre-discharge sample collection
because it is painless to collect. Additionally, protocols using
these specimen types show superiority to those using blood
specimens in the areas of collection, transport, storage and
overall cost. Further, PCR amplifications of DNA collected by
buccal swab are not subject to inhibition by heme. A dried buccal
swab is amenable to subsequent DNA analysis for at least five years
and it is expected that samples will be preserved for as long as
they are kept dry and away from the light.
[0057] Buccal samples are collected onto cotton or sponge swabs
which can then be blotted onto FTA paper. Alternatively, the
samples are stored on cardboard folders (see e.g., Hochmeister M,
et al., A foldable cardboard box for drying and storage of by
cotton swab collected biological samples, Arch. Kriminol. (1997)
200(34):113-20) or on flat slide-like sheets which may or may not
be provided with some type of protective covering. A hinged or
bifold sheet has been designed which may be substantially flat on
its top and bottom surfaces or may have depressions in the bottom
surface into which the sample can be placed. The sheet can be made
of paper or membrane if flat and may also be made of plastic where
depressions are preferred, or may be any other material that does
not interfere with subsequent sample extraction. The trifold paper
collection card with a tab on one side that allows for vertical
storage e.g., with the tab protruding up from the stacked cards to
allow ease of identification, is preferred as both inexpensiveand
space conserving. Other sample collection and storage means are
described in U.S. Pat. No. 5,756,126, Like the Guthrie card, these
collection devices are modified to allow for multiple sample
collection and labeling.
[0058] The genetic typing may be performed on genomic DNA,
mitochondrial DNA or may be based on typing the RNA present in a
cell. See e.g., Zang Y. H. & McCabe E. R., RNA Analysis from
Newborn Screening Dried Blood Specimens, Hum. Genet. (1992)89(3):
311-4. Further, the typing methodology may be any that is currently
used in the art, including techniques that are sequence based, size
analysis based, hybridization based or a combination thereof.
Generally, DNA samples may be amplified before analysis in a PCR or
PCR-like reaction. Genetic typing methodologies are well known and
need not be detailed herein.
[0059] A particularly powerful means of analyzing genetic
information is DNA chip technology. Generally speaking, DNA chips
comprise an array of oligonucleotide probes. Conditions can be
established such that nucleic acid will only hybridize to a given
probe if a perfect match is found. The array can comprise thousands
of oligonucleotides and the use of automated scoring techniques and
sophisticated data analysis software allow the collection of large
amounts of data very quickly. (see e.g., U.S. Pat. No. 5,827,482;
U.S. 5,821,060; U.S. 5,795,716; U.S. 5,763,599; U.S. 5,741,644;
U.S. 5,733,729; U.S. 5,733,509; U.S. 5,731,152;U.S. 5,728,532;U.S.
5,671,303;U.S. 5,632,957; U.S. 5,605,662; U.S. 5,599,668; U.S.
5,593,839; U.S. 5,571,639; U.S. 5,561,071; and U.S. 5,445,934; See
also; Wang D. G., et al., Large-scale identification, mapping, and
genotyping of single-nucleotide polymorphisms in the human genome,
Science (1998) 280 (5366): 1077-82; Hacia J. G., et al.,
Evolutionary sequence comparisons using high-density
oligonucleotide arrays, Nat. Genet. (1998)18(2): 155-8; Livache T.,
et al., Polypyrrole DNA chip on a silicon device: example of
hepatitis C virus genotyping, Anal. Biochem. (1998) 255 (2):
188-94; Pastinen T., et al., Minisequencing: a specific tool for
DNA analysis and diagnostics on oligonucleotide arrays, Genome Res.
(1 997) 7(6): 606-14; Wang J., et al., Nucleic-acid immobilization,
recognition and detection at chronopotentiometric DNA chips,
Biosens. Bioelectron. (1997) 12 (7): 587-99; Hacia J. G., et al.,
Detection of heterozygous mutations in BRCA1 using high density
oligonucleotide arrays and two-colour fluorescence analysis, Nat.
Genet. (1996) 14(4): 441-7; Schena M., et al., Parallel human
genome analysis: microarray-based expression monitoring of 1000
genes, Proc. Natl. Acad. Sci. USA (1996) 93(20): 10614-9; Southern
E. M., DNA chips: analysing sequence by hybridization to
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110-5; Stimpson D. I., et al., Real-time detection of DNA
hybridization and melting on oligonucleotide arrays by using
optical wave guides, Proc. Natl. Acad. Sci. USA (1995) 92(14):
6379-83; Pease A. C., et al., Light-generated oligonucleotide
arrays for rapid DNA sequence analysis, Proc. Natl. Acad. Sci. USA
(1994) 91(11): 5022-6); Shumaker et al., Mutation Detection by
Solid Phase Primer Extension, Hum. Mutation (1996) 7:346-54.
[0060] Another powerful means analyzing genetic information
involves the use of mass spectrometers to identify small mass
differences in PCR products that have single nucleotide
polymorphisms (SNPs). Kirpekar F., et al., DNA sequence analysis by
MALDI mass spectrometry, Nucleic Acids Res. (1998) 26(11): 2554-9.
Gene Trace Systems, Inc., for example, is able to analyze 10,000
samples a day with an error rate of one in 10,000. With a large
collection of SNPs in a multiplex PCR one can quickly and easily
genotype an individual without the necessity for time consuming
electrophoretic separation of samples.
[0061] Yet another means of analyzing genetic information is
"dynamic allele specific hybridization" or "DASH" for short. This
technique uses labeled oligonucleotides in a multiwell format that
will fluoresce when the oligonucleotide exists in a double-stranded
form, but not when it is single-stranded. Adding a single strand of
the DNA to be tested allows the strands to hybridize. The
temperature at which the strands again denature will allow
identification of the base at the SNP. This technique has the
advantage that it is technically simple, not requiring expensive
detection devices, such as mass spectrometers.
[0062] Furthermore, it is expected that DNA sequencing and
genotyping methodology will continue to evolve and will present
additional viable means of quickly genotyping an individual. See
e.g., Xu L., et al., Electrophore mass tag dideoxy DNA sequencing,
Anal. Chem. (1997) 69(17): 3595-602, Haff L. A., Smirnov I. P.,
Single-nucleotide polymorphism identification assays using a
thermostable DNA polymerase and delayed extraction MALDI-TOF mass
spectrometry, Genome Res. (1997) 7(4): 378-88; Taranenko N. I., et
al., Laser desorption mass spectrometry for point mutation
detection, Genet. Anal. (1996) 13(4): 87-94; Tang K., et al.,
Matrix-assisted laser desorption/ionization mass spectrometry of
immobilized duplex DNA probes, Nucleic Acids Res. (1995) 23(16):
3126-3 1; Griffm H. G. & Griffin A. M., DNA sequencing. Recent
innovations and future trends, Appl. Biochem. Biotechnol. (1993)
38(1-2): 147-59; Fauser S. & Wissinger B., Simultaneous
detection of multiple point mutations using fluorescence-coupled
competitive primer extension, Biotechniques (1997) 22(5): 964-8;
Fox S. A., et al., Rapid genotyping of hepatitis C virus isolates
by dideoxy fingerprinting, J. Virol. Methods (1995) 53(1): 1-9.
[0063] Any array of markers with a reasonably high probability of
individualizationis sufficient for these purposes. The markers can
be VNTRs, STR, CTRs, SNPs, microsatellites, etc. The number of
markers that can be used herein is virtually limitless and the
reader is referred to GENBANK and the literature for identification
of markers and which have been successfully used in genotyping
methodologies.
[0064] This system is designed to identify one out of a hundred or
at most one in one thousand infants. In consequence, the genotyping
need not be to such exacting specifications as in a paternity suit
or criminal context. Thus, while a 50 SNP set might be required for
paternity testing in a legal context, a 24 SNP set would be
sufficient for infant identification purposes. For example, a set
of three multiplex amplifications as follows will suffice for these
purposes:
1 Set 1: METH HSD3B ARSB PROS1 ADH3 BCL2 LPL LDLR IGF2 PRP (D21S13)
(APOB) Set 2: FUT1 DUF-1 D2S1301 D3S2344 WI-1417 TCRVB17 D7S1760
(D2S1415) (D10S1257) Set 3: CPT1 DNASE1 CETP-1 COL2A1 APOC3 CA2
TCRVB12 (EK2) () not currently used.
[0065] All publications cited herein are expressly incorporated by
reference. The specification and examples should be considered
exemplary only with the true scope and spirt of the invention
suggested by the following claims.
[0066] It is noted that all documents referenced herein are
incorporated herein by such reference for all purposes
whatsoever.
* * * * *