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Parentage testing using DNA

Authors
Elizabeth S Panke, MD, PhD
Alan E Donnenfeld, MD
Section Editor
Louise Wilkins-Haug, MD, PhD
Deputy Editor
Vanessa A Barss, MD, FACOG
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Feb 2015. | This topic last updated: Jun 25, 2013.
INTRODUCTION The number of parentage test cases processed by laboratories in the United
States is rapidly increasing due, in part, to advances in DNA and information technology. The
AABB (formerly the American Association of Blood Banks) reported that 414,843 paternity tests
were performed in 2008 [1].
Physicians should become knowledgeable about DNA parentage testing, as they will undoubtedly
face situations where they need to understand the process, results, accuracy, limitations, and
implications of testing. Court-ordered parentage testing is becoming more common. In addition,
patients will ask for these tests or for help with interpretation of test results since DNA testing is
now directly available to the general public.
Regulation of DNA parentage testing laboratories is limited; external oversight and accreditation
of these laboratories are voluntary. As a result, the quality, thoroughness, interpretation of
results, and admissibility of the information in court from DNA parentage testing laboratories
vary from laboratory to laboratory. In this environment, it is important that the physician and
the patient abandon the pervasive belief that all DNA tests produce extremely accurate, totally
conclusive, and irrefutable answers.
APPLICATIONS From a historical perspective, the primary objective of parentage testing was
to determine whether a man accused of paternity (ie, alleged father) could be accurately
excluded as the biological father of a given child. More than 99 percent of falsely accused men
can be excluded of paternity by using systems of red cell antigens, serum proteins, red cell
enzymes, and HLA [2].
Actual proof of paternity is not possible with any laboratory test because there is always a
chance that another man could have the same test results as the alleged father since the
number of markers tested is limited. However, advances in DNA technology have made it
possible for DNA parentage testing to produce highly conclusive evidence of parentage or
absence of parentage.
The most common situations in which parentage testing may be performed include:

Court ordered DNA analyses to determine responsibility for child support and custody
rights. If the father is deceased, the test may be used to obtain Social Security,
veteran's, or insurance benefits or settle an inheritance dispute for the child. Court
ordered DNA analyses are also performed in criminal cases involving sexual abuse of a
minor resulting in pregnancy.

Determination of a child's biological parents. These cases usually involve adoption,

immigration, and citizenship issues. They may also be related to assisted reproduction
procedures (eg, in vitro fertilization) or, rarely, newborns misidentified in the hospital or
kidnapped.

Prenatal paternity testing for pregnant women who are unsure who has fathered their
child.

Occasionally, laboratory test results reveal the unexpected finding that the father is not the
biological father of a child. Management of this situation can be complicated, and is addressed
below (see 'Disclosure of false paternity' below).
COST The laboratory fees for DNA paternity tests typically range from $400 to $600 in the
United States; most insurance plans do not cover these costs. The cost of ultrasound
examination plus amniocentesis or chorionic villus sampling adds to the cost of prenatal
paternity testing (by about $2000) and is not covered by insurance unless these tests are
performed for standard indications, such as increased risk of Down syndrome or presence of a
congenital anomaly.
SAMPLE COLLECTION AND PROCESSING Since DNA is present in most cells of the body, a
variety of cell types may be collected for DNA parentage testing. Samples are usually obtained
from the inside of the mouth with a cotton or a Dacron swab due to the ease of collection. Blood
samples may also be submitted for testing; just a few drops of blood from a finger or a heel
prick are sufficient. For prenatal DNA parentage testing, a fetal sample is collected from amniotic
fluid (5 to 10 mL) by amniocentesis or by chorionic villus sampling (CVS); thus, prenatal DNA
paternity testing can be performed as early as the late first trimester. The fetal cells can be
submitted directly to the DNA testing laboratory, or they can be sent to a cytogenetics laboratory
for culture before they are forwarded for paternity analysis. Noninvasive prenatal diagnosis using
cell free fetal DNA in maternal blood is possible, but remains investigational (see 'Noninvasive
prenatal paternity testing' below).
Sample collection procedures are an integral part of the DNA parentage testing process. The
legal ramifications of DNA parentage test results require that sample collections conform to strict
chain-of-custody procedures. These collection procedures dictate the:

Selection of the person collecting the samples

Documentation of the identity of the tested individuals

Tracking of the sample during the collection and testing process

Unfortunately, thousands of sample collections are performed for DNA parentage tests that do
not conform to the documentation of identity and chain-of-custody procedures described below.
As an example, numerous laboratories offer home testing kits that allow for anonymous testing
and for sample collections without the involvement of laboratory personnel or other
professionals. These tests are sometimes referred to as "curiosity testing" as opposed to "courtapproved tests."

Collection personnel An important first step in the proper collection of samples is the
selection of the individual(s) performing the sample collection. The Standards for Parentage
Testing Laboratories published by the AABB state: "all biologic samples for testing shall be
collected by persons with no interest in the test outcome" [ 3].
Identification of test subject The tested individuals must be properly identified and the
method of this identification must be documented. The AABB's Standards for Parentage Testing
Laboratories procedures require that the tested individual must present government photo
identification and/or the tested person's photograph can be taken at the time of sample
collection. Since government photo identifications do not always reflect the most recent and
accurate appearance of the tested individual, identity is best documented with a photocopy of
government photographic identification accompanied by the tested individual's photograph taken
at the time of sample collection.
Specimen Each collected sample must be clearly identified through an affixed label
containing a unique identification for the collected sample, the date of collection, and initials of
the person collecting the sample. The person who provides legal consent for the collection of the
sample must verify the accuracy of the affixed label in writing [ 3]. Strict chain-of-custody
procedures also apply. Samples may never be left out of sight. They must be sealed in a tamperevident package immediately following sample collection. Test participants may not package or
transfer the samples to the testing laboratory.
Prenatal testing A request from a pregnant woman to determine the identity of the father of
her fetus is becoming a more common event. Some women may use the test to terminate
pregnancies that have arisen from a sexual assault or from an extramarital relationship. Others
may use the information in legal proceedings, such as custody, child support, and inheritance
rights.
Whatever the motivation for requesting prenatal paternity testing, an obstetrician is under no
obligation to perform or become involved in such testing if it violates his or her moral, ethical,
religious, or professional beliefs. The obstetrician can notify the patient that he/she does not
participate in prenatal paternity testing and refer her to another physician who may be able to
assist her.
To perform prenatal paternity testing, biologic samples from the mother, fetus (by amniocentesis
or CVS), and at least one suspected father are required. Testing may only be performed if a
court order or informed consent from all adults involved has been obtained. The principle of
autonomy and the confidentiality established by the doctor-patient relationship mandate that
there is no obligation to inform the patient's partner (or husband) that paternity is an issue in
the pregnancy.
Noninvasive prenatal paternity testing Noninvasive prenatal paternity testing is possible
[4-6]. In 2011, a non-invasive prenatal paternity test became commercially available [ 6]. This
test can be done as early as 9 weeks of gestation, requires only a blood sample from the
pregnant mother and alleged father(s), and costs $1625 in the United States. Cell-free fetal DNA
isolated from the plasma of the mothers blood is analyzed using a dense microarray chip that
examines 317,000 genetic markers known as single nucleotide polymorphisms (SNPs). An
informatics algorithm is used to compute the similarity of genetic markers between the fetal DNA
and the alleged fathers DNA, as well as to unrelated random individuals. Although the
methodology appears sound, results of peer reviewed clinical trials are not available, and there
are no AABB professional guidelines for the use of such parentage testing, methodology
standards, and proficiency testing. We do not endorse the use of such tests prior to
comprehensive scientific and medical review [7].

PATERNITY TESTING Although the extent of misattributed paternity is unknown, estimates

are surprisingly high and generally range from 5 to 20 percent [ 8]. A series reported by the
AABB and including over 300,000 tests found that the average paternity exclusion rate for
laboratories reporting exclusions was 27.4 percent [ 9].
DNA parentage testing typically analyzes nuclear DNA. Although each individual has a unique
sequence of nuclear DNA (except identical twins), more than 99.9 percent of the information
present in the human genome is shared by unrelated individuals. Parentage testing using DNA
analysis identifies variable regions of DNA (DNA polymorphisms) in the remaining 0.1 percent of
our genetic material and then compares these sequences for different individuals.
DNA length polymorphisms One of the most useful types of polymorphic DNAs in
parentage testing is length polymorphism. Length polymorphisms occur when small sections of
DNA sequences are repeated numerous times in a row at a specific locus. The number of times
these tandem DNA units are repeated produce alleles that are shorter in some people and longer
in others. Two fragment lengths can be identified in each individual at the specified locus, one
from each chromosome of the pair.
These tandemly repeated regions of DNA are typically classified into several groups depending
on the size of the repeat region. Minisatellites (also called "variable number of tandem repeats"
[VNTRs]) have core repeats with 9 to 80 base pairs, while microsatellites (also called "short
tandem repeats" [STRs]) contain 2 to 5 base pair repeats. Paternity testing laboratories have
moved primarily towards the analyses of tetranucleotide STRs, which may be amplified using the
polymerase chain reaction (PCR). Millions of copies of DNA fragments of interest are rapidly
produced using this technology. These PCR-generated fragments are then sorted by size through
electrophoresis and the specific fragment lengths are identified.
At any specified genetic locus, two fragment lengths can be identified in each individual, one
from each chromosome of a homologous pair. When reading DNA test results, it is important to
first compare the allele sizes of the child and mother. One of the alleles in the child must match
one of the alleles in the mother since the child must have received one-half of its DNA from the
mother. The child's remaining allele can only have been inherited from the biological father and it
is called the "obligate paternal allele."
Paternity index The paternity index (PI) is the ratio of the chance that the alleged father will
pass a marker gene to the child compared to the chance that a random man will pass the marker
gene to the child. The frequency of distribution of individual marker genes for a randomly
selected man is determined from a database.
If the tested man does not have the child's obligate paternal allele, the observed pattern is
inconsistent with paternity (table 1). The observed inconsistency at the specified locus is
documented by a PI of zero (table 2). An opinion of nonpaternity should not be rendered on the
basis of a genetic mismatch at a single DNA site, or even when the mismatch involves two sites,
especially when all remaining tested systems yield a large combined paternity index (discussed
below). Most such occurrences merely reflect de novo genetic mutations that occur naturally in
normal people. In cases where there are only one or two mismatches, the PI value at a single or
double mismatching genetic site is not documented as zero, but calculated using equations that
incorporate the mutation rate at the specified genetic site. For typical DNA-RFLP and -STR
systems, average mutation rates range from 0.005 to 1 percent [ 10].
DNA family relationship testing laboratories usually require that a minimum of three genetic
mismatches between the alleged father and the child be present prior to rendering the diagnosis
of nonpaternity, as three or more de novo mutations would be exceedingly rare (table 2).

When a genetic match is identified between the tested man and a child, a PI is calculated to
determine the likelihood of a coincidental match (table 3). The PI utilizes information on the
frequency of any one particular allele in the general population. When the paternal allele seen in
the child is abundant in the population at large, a coincidental match (or a match by chance) is
not unusual so the PI is low.
Combined paternity index (CPI) The final analysis combines all of the genetic evidence
and is a product of all of the individual PI values for both mismatches and matches. This is the
bottom-line result of the DNA paternity test and it is called the Combined Paternity Index (CPI).
The CPI is a ratio of the chance that the tested man, given his entire analyzed genetic makeup,
is the biological father compared to the chance that a random man is the biological father.
At what percent of probability does one feel reasonably secure in concluding that the tested man
is the child's biological father? Currently, a CPI of 100 is the minimum required to establish
parentage for legal purposes in most states. What does this level of test result really mean?
A CPI of 100 means that the tested man is 100 times more likely to be the biological father than
a random man in the general population. For a CPI of 100, the Random Man Not Excluded
(RMNE) statistic value would also equal approximately 100 and it would be expressed as "one
individual in 100 has the same genetic pattern as the tested man," and the probability of
paternity that the tested man is the biological father would be 99 percent. At this level, which is
the minimum legal standard, 1 out of approximately 100 individuals in the population has the
same genetic pattern as the tested man, and therefore could be the biological father.
A number of laboratories believe that the minimum CPI required for legal establishment of
parentage should be raised from a CPI of 100 (probability of paternity 99 percent) to a CPI of
1000 (probability of paternity 99.9 percent) to determine the biological father with a reasonable
degree of certainty and to decrease the rate of false positive paternity results (table 4). The
following examples illustrate cases of incorrect attribution of paternity:

One study used a 9- or 15-genetic STR loci test to test 249 men known not to be the
child's father [11]. Among the 249 non-fathers, one matched the child on all nine
genetic sites and had a CPI of 298 and 99.66 percent probability of paternity. Another
man had a probability of paternity of 99.72 percent (CPI of 353) when 15 genetic sites
were tested.

A case reported at the Twelfth International Symposium on Human Identification

involved a man accused of sexual assault whose DNA paternity test result showed a 99.3
percent probability of paternity [12]. Only with additional testing was this man excluded
as the biological father of the child resulting from the sexual assault.

Another report at the symposium was a case from the Arizona Public Safety Crime
Laboratory that identified a match between two unrelated offenders, one Caucasian and
the other African-American, who shared both alleles at nine genetic loci [ 13]. The
Florida State Crime Laboratory has also reported a nine-genetic loci match between two
unrelated individuals [14].

A CPI of 1000 (probability of paternity 99.9 percent) is possible in virtually all cases when the
child, the child's mother, and the alleged father are tested at 13 independent genetic sites that
include the CODIS loci. If testing is limited to samples collected from only the child and the
alleged father (the mother's sample is not tested), a CPI of 1000 is not reached in up to 10
percent of cases. The need to collect and test the mother's sample in these cases to reach a CPI
of 1000 increases testing costs. If the mother is absolutely unavailable for testing, the laboratory
would be required to test several additional genetic sites between the child and the alleged

father before a CPI of 1000 could be reached in most cases, which also increases testing costs.
(See 'Options when a maternal specimen is not available' below.)
Evidence suggests that gains in adopting a minimum standard CPI of 1000 outweigh the costs,
as reflected by several states increasing their standards for the presumption of paternity. Hawaii
and Illinois increased the established presumption of paternity to a CPI of 500 (probability of
paternity 99.8 percent); Louisiana has increased the established presumption of paternity to a
CPI of 1000 (probability of 99.9 percent).
Another significant benefit of an extensive DNA test is that it is more reliable in excluding falsely
accused men who are relatives of the biological father, such as a brother, father, or son. This is
important because laboratories are often given the opportunity to only test one of the alleged
fathers.
In an ideal world, laboratories would provide extensive testing in all cases and would test to a
level of certainty of at least 99.9999999 percent, thereby removing any doubts of paternity.
Technology is available to provide that level of certainty in every case. Paternity testing
laboratories, however, have an economic incentive to keep the level of testing as low as possible.
Probability of paternity Probability of paternity is another statistical means of describing
the likelihood that the alleged father is the biological father of the child. It incorporates both
genetic (CPI) and nongenetic (prior probability) information. Prior probability assigns a numerical
value from 0 to 1 to the non-genetic evidence used in evaluating paternity; a prior probability of
zero is impossible paternity, 0.5 is considered neutral, and 1 is certain paternity. When prior
probability is 0.5, the formula for calculating probability of paternity is 1/[1+1/CPI].
Random man not excluded An easier way of expressing these figures is the RMNE statistic,
which closely approximates the CPI. The RMNE is the frequency with which men selected at
random from the same racial group as the alleged father would not be excluded as the biological
father of the child by the given DNA paternity test.
Alleged fathers who are brothers A DNA testing laboratory must always be informed about
situations in which two alleged fathers are related as brothers. DNA paternity tests cannot
distinguish the true biological father in cases where two alleged fathers are monozygotic twins
because monozygotic twins have identical nuclear DNA. When two alleged fathers are related as
full siblings, they share half of their genetic makeup. In such cases, the most conclusive DNA
paternity test results are obtained when both alleged fathers undergo DNA paternity testing: the
DNA testing laboratory continues testing until one of these alleged fathers shows at least three
genetic mismatches with the tested child.
Sometimes the two alleged fathers are related as brothers and only one alleged father is
available for DNA testing. In such cases, the DNA testing laboratory typically performs extended
DNA testing analyzing a minimum of 15 to 24 genetic sites and the child's mother's sample is
also tested (unless her sample is unavailable). Such extended testing and testing of the child's
mother allow DNA testing laboratories to exclude a falsely accused brother from paternity in
most cases; however, absolute certainty of exclusion in such cases can only be achieved when
both brothers are tested.
Additionally, upon request, the DNA testing laboratory can provide the avuncular index
calculation along with the paternity index calculation on the DNA test report. Such reports will
show how much more likely it is that the tested man is the biological father of the child versus
the child's uncle.

OPTIONS WHEN THE FATHER IS NOT AVAILABLE

Grandparent testing In cases where the alleged father is deceased or missing, both of his
parents can be tested to determine the likelihood they are the child's paternal grandparents. The
deceased alleged father received his genes from his parents; therefore, the child's paternal
alleles will match the alleles in the alleged paternal grandfather and grandmother in cases where
the deceased man is the true biological father of the child and true biological child of the
grandparents.
If the child's paternal alleles do not match the alleged grandparents' alleles on at least three
different genetic sites, the DNA test for grandparentage proves conclusively that the tested
grandparents are not the paternal grandparents of the child. In such cases, we can presume the
deceased alleged father could not be the child's biological father. This presumption is only valid
when the tested paternal grandparents are true biological parents of the deceased alleged father
of the child.
If the alleged paternal grandparents' alleles match the alleles of the child, the probability of
grandparentage is determined. The calculations for the probability of grandparentage are based
on gene frequencies of the matching alleles. The DNA test for grandparentage has the ability to
reach probabilities of grandparentage far in excess of 99.9 percent. However, there are some
limitations to this testing. As an example, the DNA test for grandparentage cannot resolve
paternity if two potential fathers are related as full brothers, and therefore, have the same
parents.
If only one alleged grandparent is available, testing is problematic. As a couple, the two paternal
grandparents collectively match the child on one half of the child's genes, while a single
grandparent only matches 25 percent of the child's genes. Therefore, when only one alleged
grandparent is tested with the child, it is impossible for the testing laboratory to conclusively
prove that the tested alleged grandparent is not the child's grandparent. True and false
grandparentage relationships in these cases cannot be distinguished using the DNA test result
interpretation criteria described above for DNA parentage tests. Evaluation of these cases is
complicated and beyond the scope of this topic review.
Family reconstruction test A DNA family reconstruction test is another means of
determining paternity when the alleged father is deceased or missing. Such DNA testing is
possible because the genes of the deceased or missing alleged father are present in his known
biological family members (siblings, known children, parents).
The deceased or missing alleged father can be excluded with absolute certainty as the biological
father of the child by the DNA test for family reconstruction. Alternatively, the DNA test for
family reconstruction can demonstrate greater than 99.9 percent probability that the deceased
or missing alleged father is the biological father of the child. Such probabilities of paternity can
be reached only if a sufficient number of family members with known relationships to the alleged
father is available for testing.
Extended family studies should only be ordered in consultation with experienced DNA laboratory
scientific professionals. The capacity to achieve conclusive DNA test results in extended family
DNA testing depends on thorough understanding of the alleged family's clinical information, in
depth knowledge of genetics, and expertise in the most current DNA testing technology. Testing
large, genetically diverse DNA sites is labor intensive, time consuming and costly for the testing
laboratory.

Sample case Consider the following example where the alleged father is deceased. The
deceased man's wife and their two known biological children are available for testing. Another
child whose biological father is in question, and this child's mother, are also tested.
The first laboratory tested 17 DNA sites and also performed HLA testing (table 5), and their
results showed a relatively low probability of paternity of 57.2 percent (CPI 1). An inexperienced
observer can easily become impressed with the shear number of tested genetic sites and be
convinced that the best possible DNA test was performed. Notice, however, that the first
laboratory limited their testing to genetic sites very commonly present in most individuals within
the population. DNA testing of these common genetic sites is done through a highly automated
system, and therefore is the most cost effective method of testing for the laboratory.
The second laboratory performed DNA testing on the same individuals. However, the second
laboratory chose to test large, highly diverse genetic sites that are not commonly shared by
many individuals within the population. As a result, the second laboratory produced highly
conclusive probability of paternity of 99.999 percent (CPI 99,807) (table 6).
Sibling test In the DNA sibling test, two children are tested to determine whether they share
the same biological parent or parents. Each of a child's genes matches genes of a biological
parent. Since the mother and the father have two copies of each gene, they may donate
different copies to different children.
True full siblings who share the same mother and father have about a 25 percent chance of not
sharing the genetic information at any one genetic site in a DNA sibling test. True half siblings
who share one parent have a 50 percent chance of not sharing any markers at any one genetic
site in a DNA sibling test. Therefore, the DNA testing laboratory cannot report with absolute
certainty that two individuals are not related as siblings when only two alleged siblings are
available for testing.
DNA tests for determination of biological sibling relationships between two tested individuals
have their own criteria for test result interpretation and for determination of the likelihood of a
sibling relationship. The criteria as to whether the two tested individuals are true full/half siblings
or unrelated individuals claiming to be siblings are derived from studies of cohorts of true
siblings and from studies of cohorts of matched unrelated individuals. The data generated from
these DNA sibling studies are classically summarized with the Combined Sibling Index (CSI)
statistic. The CSI indicates the likelihood that the tested alleged individuals are siblings versus
being unrelated. For example, the CSI of 64,236 indicates that the likelihood is 64,236 to 1 that
the tested alleged siblings are true siblings versus being unrelated.
When only two individuals are tested, DNA sibling tests often show very high CSI, and such DNA
sibling test results are easy to interpret since the data are statistically pointing toward a positive
full sibling relationship. However, true full siblings can have "single digit" CSI values. In fact,
studies of cohorts of true full siblings and studies of cohorts of matched unrelated individuals
have shown that when only two individuals are tested, the statistical evidence supports the
conclusion that the two individuals are related as true full siblings when the CSI is equal to or is
greater than 1 [15-17]. In one study, less than 1.61 percent of true full sibling pairs had CSI
values of less than 1 [15], but another study reported that 1.6 percent of random, unrelated
pairs were found to have a CSI between 1 and 3 [18].
When only two individuals are tested, studies of cohorts of true half siblings and studies of
cohorts of matched unrelated individuals have shown that a combined CSI of approximately 30
or higher is characteristic of individuals who are related as half siblings [ 19]. Another study
found that up to approximately 13 percent of CSI values are less than 1 in those individuals who

are half siblings and that up to 13 percent of CSI values are greater than 1 in those individuals
who are not related [15]. Studies of cohorts of true siblings and studies of cohorts of matched
unrelated individuals suggest that CSI of less than 0.1 is fairly characteristic of unrelated
individuals who claim to be siblings [16,19].
In cases where DNA sibling test results are uninformative, the conclusiveness of DNA sibling test
results can be greatly improved by testing additional known family members. For example,
testing known biological parents of one (or both) of the siblings in addition to testing the two
alleged siblings greatly improves the ability of the DNA testing laboratory to provide definitive
sibling answers. Also, the DNA testing laboratory has the ability to reconstruct the complete
genetic makeup of biological parents (ie, genetic makeup of entire family) when DNA specimens
are available for study from several known siblings in a family.
An alternative strategy is to investigate the paternal and/or maternal lineages of the tested
alleged siblings by performing supplemental DNA testing using sex-linked DNA polymorphisms
on the Y chromosome or in mitochondrial DNA, respectively.
Y-STR DNA test The Y-STR paternal lineage DNA test can be used to determine whether two
or more males are related through their paternal lineage. The Y chromosome is passed from
father to son and has a relatively infrequent mutation rate, thus, it remains the same through
many generations. The Y-STR paternal lineage DNA test examines specific sites on the Y
chromosome and yields a unique Y-STR profile for each male tested. Males who are related
through their fathers tend to have the same Y-STR profiles, and males who are not related tend
to have different Y-STR profiles.
It is important to remember that the Y-STR paternal lineage DNA test does not differentiate who
the child's biological father is in cases where the two alleged fathers are paternally related.
However, the Y-STR paternal lineage DNA test can be particularly useful for excluding males from
an alleged biological relationship. As an example, in cases where the alleged father is missing
and cannot be tested, Y-STR profiles of a male child and his alleged uncle (brother of the alleged
father) are compared. If the two Y-STR profiles do not match, then the alleged father is very
likely not the biological father of the child.
OPTIONS WHEN A MATERNAL SPECIMEN IS NOT AVAILABLE A DNA paternity test can
be performed by testing the specimens collected from the child and from the alleged father,
without a DNA sample from the mother. This may be necessary when the mothers location is
unknown, she refuses to participate in the testing, or she is deceased. The DNA test results
obtained from a motherless paternity test can be as accurate as those of a paternity test
performed on specimens of the mother, child, and alleged father; however, the motherless test
requires more extensive analysis to produce conclusive results. In motherless paternity tests,
the relationship index is, on average, cut in half for each genetic locus tested. Therefore, not
testing the mother greatly reduces the ability to exclude paternity.
It is also important to test the mothers specimen in cases of incest since such cases are liable to
produce false inclusions. Additionally, the mothers participation in paternity testing aids in the
analysis of unexpected results. Her participation is especially helpful when an apparent
inconsistency (mutation) is present. In some cases of genetic mutations, it may not be possible
to render an opinion of paternity without obtaining a specimen from the mother. The mother is
also an important quality control step in the paternity test.
Including the mothers specimen in a DNA paternity test, even if maternity is not disputed, is
important in evaluating the questioned relationship. It improves the chances of obtaining
definitive DNA paternity test results and it serves as an important quality control check. DNA

paternity testing without the mother should be done only when the mothers location is unknown
or if she is deceased.
DISCLOSURE OF FALSE PATERNITY Occasionally, laboratory test results (whether
complicated molecular genetic tests or relatively simple blood typing) reveal that the alleged
father is not the biological father of a child or fetus. In 1994, the Committee on Assessing
Genetic Risks of the Institute of Medicine (IOM) recommended that in such cases, only the
mother should be informed, as "genetic testing should not be used in ways that disrupt families"
[20]. This report has received widespread support. Among a sampling of more than 500 genetic
counselors, 98.5 percent stated they would not inform the father if misattributed paternity was
revealed as a serendipitous finding on a laboratory test result [ 21].
An alternative (and proactive) approach is to raise the issue (as a hypothetical case scenario)
prior to testing and inform parents that false paternity might be identified in the performance of
a laboratory analysis. Raising the issue prior to testing allows the physician to obtain guidance as
to how to handle actual test results that may identify false paternity. Several ethicists have
argued that this is the optimal approach when false paternity is accidentally discovered [ 22].
FINDING AN ACCREDITED TESTING FACILITY Regulation of parentage testing is limited.
External oversight of laboratories is voluntary or comes about because laboratories offer other
services that are regulated. More than 160 laboratories are advertising DNA parentage testing
on the internet, but only about 44 of them are accredited by the AABB (a list of AABB accredited
laboratories can be viewed at

www.aabb.org).

The AABB is the primary organization that has established national procedures and standards for
DNA parentage testing and performs on site laboratory inspections for the purpose of
accreditation [3]. The AABB also directs an external proficiency testing program for DNA
parentage testing laboratories and provides this testing program in conjunction with the College
of American Pathologists (CAP).
Accreditation refers to the qualifications of the DNA testing laboratory. Certification refers to the
qualifications of the DNA laboratory personnel. In the United States, only the State of New York
requires mandatory certification by the New York State Department of Health (NYSDOH) for all
doctoral level professionals performing DNA parentage testing. The State of New York is also the
only state that requires DNA testing laboratories to have a physician's prescription or a court
order for each DNA parentage test they perform. The NYSDOH further requires accreditation of
all DNA laboratories performing DNA testing on individuals from the State of New York. The
NYSDOH has established procedures and standards for DNA parentage testing, performs on site
laboratory inspections, and has an established proficiency testing program [ 23].
Since DNA laboratory accreditation is voluntary outside of the state of New York, the patient
must be cognizant of the laboratory accreditation process in order to select an accredited testing
facility. The patient should also be aware that AABB accredited laboratories may retain and
proclaim their accredited status while offering some testing that does not meet standards [ 24].
Additionally, DNA parentage tests are often marketed and sold by brokers. Brokers frequently
work with a number of contracting laboratories. The contracting laboratories are often not
identified by name, making it impossible to verify their accreditation status.
ETHICAL CONSIDERATIONS The advances in today's technology summon us to redefine
the process of parentage determination. For countless generations, parentage rights were easy
to assign. The woman who gave birth to the child was the child's mother. In large measure,
paternity has been based on social, rather than biological factors. Widespread availability of

highly accurate DNA tests raises questions about whether genetic parentage testing should
replace social and childrearing tests for parenthood. In some states, statutes have been passed
that allow a genetic test to upset paternity judgments at any time in the child's life. Legal
initiatives have been proposed to allow a man to stop paying child support if a DNA paternity
test shows he is not the father [25,26]. On the other hand, men with infertility problems may
use donated semen to create a child and consider this child to be theirs despite lack of a genetic
connection. In fact, assisted reproduction techniques create situations where a child may have
several "parents," such as an egg donor, sperm donor, gestational carrier, and the couple who
intend to raise the child. Clearly, we need to reanalyze our definition of parentage.
The process of parentage determination also raises a number of other issues. There are
questions about who should be able to order DNA parentage testing, and under what
circumstances. Should an individual be able to use a hair follicle from a comb, or collect a buccal
swab from a minor child and test the child's DNA without their custodian's knowledge or
consent? Should presumed fathers be allowed to surreptitiously test children without maternal
consent? Should divorced fathers and lovers use DNA testing to reopen previously agreed-upon
child support responsibilities?
Genetic testing has the potential to be highly disruptive to families, and to children who may find
themselves cut off financially and emotionally from the persons they consider parents. To
address some of these issues, a collaborative project was initiated between The Hastings Center
and the Institute For Bioethics, Health Policy and Law at the University of Louisville, supported
by a grant from the National Human Genome Research Institute of the National Institutes of
Health [27]. The objective was to develop a public policy framework to address the difficult
ethical and legal issues raised by technology used to determine parentage. The following
recommendations resulted from this research [28]:

Parentage testing should only be performed by accredited laboratories and all testing
should be done in accordance with accreditation standards.

There should be a flat prohibition on parentage testing without consent or court order.

Laboratories should be required to obtain documentation of authority. In cases where the

DNA parentage test is performed by order of a tribunal, the court order for DNA testing
is providing consent to testing. For cases where there is no court order for DNA testing,
the specimen collector must obtain written informed consent, according to applicable
law, from each tested individual prior to specimen collection.

The AABB "Guidance for Standards for Relationship Testing Laboratories" states: "testing may be
ordered by a physician or attorney without a court order [29]. Each physician or attorney is
responsible for informing his or her clients as to any risk involved in relationship testing. The
laboratory should provide the physician or attorney with guidance. For cases where there is no
court order and the persons being tested are the laboratory's clients, the laboratory is required
to obtain consent for all participating individuals to indicate that they had knowledge of and
granted consent for the test. Written authorization should be obtained prior to or at the time of
sample collection. Laboratories should be familiar with the applicable state laws and regulations
governing consent/competency."

Standards for parentage testing should be complemented by a criminal law covering

unauthorized testing. Adoption of such legislation at the federal level would ensure that
all DNA parentage testing is performed in accordance with uniform standards of technical
proficiency and ethical principles.

SUMMARY AND RECOMMENDATIONS

DNA parentage testing is primarily used to determine whether a man can be conclusively
excluded as the biological father of a given child. There are legal, financial, and social
indications for obtaining this information. (See 'Applications' above.)

Biologic samples for DNA parentage testing must be obtained and processed using a
strict chain-of-custody protocol. (See 'Sample collection and processing' above.)

Parentage testing uses tandemly repeated DNA length polymorphisms to compare DNA
samples between individuals. (See 'DNA length polymorphisms' above.)

Samples from the child, mother, and alleged father are used. Alleles not shared by
mother and child represent obligate paternal alleles. (See 'DNA length polymorphisms'
above.)

When the alleged father is not available, DNA grandparentage testing can produce highly
conclusive results. (See 'Grandparent testing' above.)

Alternatively, family reconstruction by DNA analyses can provide highly conclusive

results if a sufficient number of family members with known relationship to the deceased
is available for testing and if a sufficient number of highly diverse genetic sites is tested.
(See 'Family reconstruction test' above.)

The combined paternity index (CPI) is the ratio of the chance that a tested man, given
his entire analyzed genetic makeup, is the biological father of the child in question,
compared to the likelihood of a random man producing the child. A CPI of 1000
(equivalent to a probability of paternity of 99.9 percent) means that odds are 1000 times
to 1 that the tested man is the biological father in comparison to a random man in the
general population. A combined paternity index of 1000 should be utilized as a minimum
requirement to establish paternity. (See 'Paternity index' above.)

The Random Man Not Excluded (RMNE) statistic closely approximates the CPI. For a CPI
of 1000, the RMNE statistic value would also equal approximately 1000 and it would be
expressed as "one individual in 1000 has the same genetic pattern" as the tested man.
(See 'Random man not excluded' above.)

The Y-STR paternal lineage DNA test can be used to determine whether two or more
males are related through their paternal lineage. (See 'Y-STR DNA test' above.)

An opinion of non-paternity should not be rendered on the basis of a genetic mismatch

at a single DNA site. A minimum of three genetic mismatches between the alleged father
and the child should be present prior to rendering the diagnosis of non-paternity. (See
'Paternity index' above.)

Prenatal paternity testing requires informed consent from all adults involved in testing,
samples from the mother, one of the potential fathers, and the fetus (by either CVS or
amniocentesis). In other situations, legal standards for consent may not exist, but
experts believe parentage testing without consent or court order is unethical. (See
'Prenatal testing' above and 'Ethical considerations' above.)

Regulation of DNA parentage laboratories is voluntary. The AABB (formerly the American
Association of Blood Banks) is the primary organization that has established national
standards for DNA parentage testing and performs on site laboratory inspections.

Parentage testing should only be performed by accredited laboratories and all testing
should be done in accordance with accreditation standards. (See 'Finding an accredited
testing facility' above.)
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14 Florida State Crime Laboratory, personal communication.

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29

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Topic 425 Version 8.0

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