Incest diagnosis by comparison of alleles of mother and offspring at highly heterozygous loci.

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.