DNA Technology in Forensic Science (1992) / Chapter Skim
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3 DNA TYPING: STATISTICAL BASIS FOR INTERPRETATION
3 DNA TYPING: STATISTICAL BASIS FOR INTERPRETATION
Pages 74-96
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From page 74... ...
that match at the small number of sites examined. Nonetheless, even with today's technology, which uses 3-5 loci, a match between two DNA patterns can be considered strong evidence that the two samples came from the same source.
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Because estimates used in forensic science should avoid placing undue weight on incriminating evidence, an upper confidence limit of the frequency should be used in court. This is especially appropriate for forensic DNA typing, because any loss of power can be offset by studying additional loci.
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Estimating Frequencies of DNA Patterns with the Multiplication Rule (Product Rule) In contrast, population frequencies often quoted for DNA typing analyses are based not on actual counting, but on theoretical models based on the principles of population genetics.
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In contrast, highly polymorphic DNA markers exceed the informative power of protein markers, so multiplication leads to estimates that are less than the reciprocal of the size of the databases. Validity of Multiplication Rule and Population Substructure The multiplication rule is based on the assumption that the population does not contain subpopulations with distinct allele frequencies-that each individual's alleles constitute statistically independent random selections from a common gene pool.
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(In the context of forensic applications, an estimate of the probability of a match in DNA typing has been termed conservative if on the average it is larger than the actual one, so that any weight applied to the estimate would favor the suspect. Thus, some laboratories use a more conser I- - 1 vative rule for counting population frequencies than for forensic matches an acceptable approach, because it overestimates allele frequency.
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Basis of Concern About Population Substructure The key question underlying the use of the multiplication rule is whether actual populations have significant substructure for the loci used for forensic tYninc. This has provoked considerable debate among Population .
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Moreover, pairwise comparisons of all five-locus DNA profiles in the FBI database showed no exact matches; the closest match was a single three-locus match among 7.6 million pairwise comparisons.~3 These studies are interpreted as indicating that multiplication of gene frequencies across loci does not lead to major inaccuracies in the calculation of genotype frequency at least not for the specific polymorphic loci examined. Although mindful of the controversy, the committee has chosen to assume for the sake of discussion that population substructure may exist and provide a method for estimating population frequencies in a manner that adequately accounts for it.
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directly sample different groups and compare the observed allele frequencies. The third offers the soundest foundation for assessing population substructure, both for existing loci and for many new types of polymorphisms under development.
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The Ceiling Principle: Accounting for Population Substructure We describe here a practical and sound approach for accounting for possible population substructure: the ceiling principled It is based on the following observation: The multiplication rule will yield conservative estimates, even for a substructured population, provided that the allele frequencies used in the calculation exceed the allele frequencies in any of the population subgroups. Accordingly, applying the ceiling principle involves two steps: (1)
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From page 83... ...
Note that the frequency used for allele c is 5%, rather than 4%, to reflect the recommended lower bound of 5% on allele frequencies. Because the calculation uses an upper bound for each allele frequency, it is believed to be conservative given the available data, even if there are correlations among alleles because of population substructure and even for persons of mixed or unknown ancestry.
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A collection of 100 randomly chosen people provides a sample of 200 alleles, which is quite adequate for estimating allele frequencies. · Genetically homogeneous populations from various regions of the world should be examined to determine the extent of variation in allele frequency.
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A conservative approach imposes no fundamental limitation on the power of the technique. DETERMINING ALLELE FREQUENCIES IN A POPULATION DATABANK For forensic purposes, the frequency of an allele in a laboratory's databank should be calculated by counting the number of alleles that would be regarded as a match with the laboratory's forensic matching rule, which should be based on the empirical reproducibility of the system.
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Paternity testing with DNA typing is already an active industry in the United States, and grandmaternity testing (with mitochondrial DNA, as well as nuclear genes) has been used in Argentina to reunite families with children who were abducted during the military dictatorship in the 1970s.23 24 Relatedness testing involves a question analogous to that asked in identity testing: What is the chance that a randomly chosen person in the population would show the degree of relatedness expected of a relative?
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· Finally, the genetic correlation among relatives warrants caution in the statistical interpretation of DNA typing results. Our discussion above focused on the probability that a forensic sample would by chance match a person randomly chosen from the population.
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Such outcomes represent a dramatic success of the new technology and often lead to the exoneration of innocent suspects. LABORATORY ERROR RATES Interpretation of DNA typing results depends not only on population genetics, but also on laboratory error.
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TOWARD A FIRM FOUNDATION FOR STATISTICAL INTERPRETATION Statistical interpretation of DNA typing evidence has probably yielded the greatest confusion and concern for the courts in the application of DNA to forensic science. Some courts have accepted the multiplication rule based on the grounds of allelic independence, others have used various ad hoc corrections to account for nonindependence, and still others have rejected probabilities altogether.
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Adequate empirical data must be collected, and appropriate adjustments must be made to reflect the remaining uncertain ties. · It is feasible and important to estimate the degree of variability among populations to determine ceiling frequencies for forensic DNA markers and to evaluate the impact of population substructure on genotype frequencies estimated with the multiplication rule.
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Reporting of Statistical Results Until ceiling frequencies can be estimated from appropriate population studies, we recommend that estimates of population frequencies be based on existing data by applying conservative adjustments: First, the testing laboratory should check to see that the observed multilocus genotype matches any sample in its population database. Assuming that it does not, it should report that the DNA pattern was compared to a database of N individuals from the population and no match was observed, indicating its rarity in the population.
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From page 92... ...
We note that a 10% lower bound is recommended while awaiting the results of the population studies of ethnic groups, whereas a 5% lower bound will likely be appropriate afterwards. In the context of the discussion of the ceiling principle, the higher threshold reflects the greater uncertainty in using allele frequency estimates as predictors for unsampled subpopulations.
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From page 93... ...
Of course, if fewer than four loci were interpretable, as is common in forensic typing, the estimated genotype frequency would be much higher. Significantly more statistical power for the same loci will be available when appropriate population studies have been carried out, because the availability of data based on a more rigorous sampling scheme will make it unnecessary to take an upper 95% confidence limit for each allele frequency nor to put such a conservative lower bound (0.10)
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· As a basis for the interpretation of the statistical significance of DNA typing results, the committee recommends that blood samples be obtained from 100 randomly selected persons in each of 15-20 relatively homogeneous populations; that the DNA in lymphocytes from these blood samples be used to determine the frequencies of alleles currently tested in forensic applications; and that the lymphocytes be "immortalized" and preserved as a reference standard for determination of allele frequencies in tests applied in different laboratories or developed in the future. The collection of samples and their study should be overseen by a National Committee on Forensic DNA Typing.
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· Laboratory error rates should be measured with appropriate proficiency tests and should play a role in the interpretation of results of forensic DNA typing.
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Ferrell RE. A population genetic study of six VNTR loci in three ethnically defined populations.
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