Controlling specimen misidentification in parentage analysis.
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Biomedical subjects
Publications and source records attributed to T Houtz.
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BACKGROUND: Methods that detect a child's homozygosity by examination of allelic products are insensitive for diagnosing incest because, at a given locus, a homozygous state is expected with a frequency of only 0.25 when parents are first-degree relatives. Furthermore, these methods are not specific if the population contains many homozygous individuals or silent alleles that cause apparent homozygosity. STUDY DESIGN AND METHODS: Use of highly heterozygous loci improves specificity, but not sensitivity. Sensitivity may be increased by observing for two kinds of mother-offspring similarities: an offspring of incest tends to be homozygous or heterozygous-identical with respect to its mother's phenotype. At each locus, two conditional probabilities may be calculated for a genetic observation, using allele frequencies expected under a state of incestuous mating versus mating within a specified population. The conditional probabilities at each locus are compared in a likelihood ratio to express a relative probability of incest. RESULTS: In a case of known sibling incest, three likelihood ratios were derived from variable number of tandem repeat phenotypes at five loci. When only offspring homozygosity was observed, the likelihood ratio was 75.3:1. When both homozygous- and heterozygous-identical phenotype similarities of offspring and mother were noted, the likelihood ratio was 130.4:1. When maternal obligatory alleles of the offspring were considered, the likelihood ratio was 262.4:1. CONCLUSION: Comparison of maternal and offspring phenotypes at highly heterozygous loci increases both sensitivity and specificity of genetic tests in cases of suspected incest.
A newly discovered case of heteropaternal superfecundation (HS) is reported. Three HS cases were found in a parentage test database of 39,000 records. The frequency of HS among dizygotic twins whose parents were involved in paternity suits is 2.4%. Although the study population appears similar to the general population with respect to twinning data, inferences about the frequency of HS in other populations should be drawn with caution.
Traditional genetic marker systems rarely fail to resolve paternity disputes when two or more men are accused, except when men are brothers. A sibling of the biologic father may not be excluded by these laboratory tests and sometimes yields calculated odds of paternity that are equal to or higher than the true male parent. Resolved two-brother cases were compared with resolved cases involving two unrelated men. In each case, the residual odds of paternity were determined for each man and the greater was divided by the lesser to produce a paternity fraction. The paternity fraction is a useful indicator of biologic parentage when it exceeds a value of 10 (log10 of-the-odds score greater than or equal to 1). Tests for alleles at highly heterozygous loci are indicated in initial laboratory evaluations of cases involving brothers. Human leukocyte antigen and variable number of tandem repeat polymorphisms appear suitable.
Parentage analysis has revealed a high probability that a man accused of paternity is the biological father of a male child. The child in this study, however, was the twin of a female child who could not have been fathered by the accused man. The mother of the children subsequently accused a second, unrelated man, who was excluded from paternity of the boy, but was very probably the biological father of the girl.
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A frequent legal argument raised in defense of men accused of paternity, but not excluded by genetic tests, is that the probabilities of paternity of falsely accused men are similar to those of biologic fathers. This assertion was tested in a computer simulation experiment that used a database of 15,000 actual paternity cases to provide red cell and HLA phenotypes of mothers, children, and putative fathers. Tests had a combined probability of exclusion of 97.3 percent. Equal numbers of true and false fathers were generated from the data by computer to achieve a prior probability of paternity of 0.5. True fathers' phenotypes were those of unexcluded men from actual cases (Group A) or of mothers from actual cases (Group B) in which paternity was not excluded. The false father group was created by assigning the phenotypes of racially identical men who were selected at random from among cases other than their own. Probabilities of paternity were calculated for the men in each group and were classified into descriptive intervals. The frequency of men in each group was compared in each interval. The frequency distributions of probabilities of paternity for true fathers and unexcluded, falsely accused men (false fathers) were markedly dissimilar.