Pretense of parentage by siblings in immigration: Polesky's paradox reconsidered.

BACKGROUND: Older and younger siblings occasionally attempt to impersonate parent and child to expedite immigration under US family-based visa policies. The rate with which full siblings escape detection by current relationship tests is unknown. STUDY DESIGN AND METHODS: Retrospective study of full-sibling immigrant pairs was undertaken to determine the proportion that show insufficient genetic evidence to exclude parentage. Sibship and parentage indices (SI and PI) were compared/case in unexcluded sibling cases and true parent-child cases. Alleles shared per short-tandem-repeat locus were compared in sibling and parent-child pairs. The proportion of successful parentage fraud by siblings was estimated from the parentage exclusion rate among immigrants and the proportion of sibships without genetic inconsistencies (GIs). RESULTS: When 11 to 25 independent loci were tested per two-sibling case to verify or refute parentage, tests failed to demonstrate any GI in 9% and PI was greater than SI in seven of 10 of these cases. Another 29% of full-sibling pairs demonstrated insufficient evidence (fewer than two GIs) to exclude parentage. Thus, 0.4% of sibling pairs could falsely claim a parent-child relationship and show no GIs. Another 1.4% could make that false claim and not present sufficient evidence to be excluded. CONCLUSION: At present, with no evidence of parentage exclusion in a full-sibling pair, the relative magnitudes of PI and SI are misleading relationship indicators because too few loci are examined and rates of sharing one and two alleles/locus vary greatly in parentage and sibling pairs. Only evidence of exclusion ascertains false parentage claims by siblings. Nevertheless, the expected rate of successful fraud is quite low.

Empowering sibship analyses with reference pedigrees.

BACKGROUND: In sibship analysis, the usual comparison of an alleged (test) sibling's short tandem repeat (STR) types with those of a reference sibling may prove inconclusive. Increasing the number of examined STR loci may not change sibship probabilities very much. We increased the number of verified reference siblings to resolve problematic cases of alleged sibship. STUDY DESIGN AND METHODS: (A) Ten paternity cases were chosen in which there were three highly probable children of each alleged father. Pairs of the alleged father's children were analyzed for full sibship. The test sib with the lowest likelihood of sibship was reanalyzed by a comparison with two reference siblings combined. (B) Five problematic sibship cases are presented to demonstrate how two-person reference pedigrees can improve diagnosis over tests using one reference person. RESULTS: (A) Two-person pedigrees exponentially increased sibship probabilities of true siblings above those produced by one reference person. (B) In problem cases, reference pedigrees provided data that: (1) statistically verified some alleged sibships in which analyses using one reference person yielded inconclusive results, (2) allowed exclusion of some alleged sibships, or (3) suggested alternate blood relationships to the alleged one. CONCLUSIONS: Use of reference pedigrees often resolves sibship questions left unsettled by tests using reference individuals. Adding reference relatives is a far more powerful analytical strategy than adding test loci. Whenever possible, verified blood relatives should be incorporated into a reference pedigree to retest an alleged sibling whose initial results were unclear.

DNA microarray technology in the clinical environment: the AmpliChip CYP450 test for CYP2D6 and CYP2C19 genotyping.

INTRODUCTION: An important technological advance in genetic testing is the DNA microarray, which allows for the simultaneous testing of thousands of DNA sequences. The AmpliChip CYP450 Test employs this microarray technology for cytochrome P450 (CYP) 2D6 and CYP2C19 genotyping. Isoenzymes encoded by these genes are responsible for the metabolism of many widely prescribed drugs. The objectives of this study were to identify CYP2D6 and CYP2C19 alleles and phenotypes in a psychiatric patient population in Kentucky, and to describe practical issues associated with DNA microarray technology. METHODS: A total of 4,532 psychiatric patients were recruited from three state hospitals in Kentucky. Whole blood, buccal swabs, or saliva samples were genotyped with the AmpliChip CYP450 Test to derive a predicted phenotype. RESULTS: In this cohort, the overall prevalence of CYP2D6 poor metabolizers was 7.6% (95% CI 7%, 8.3%), 8.2% in the Caucasians (95% CI 7.4%, 9.%) and 1.8% in the African Americans (95% CI 0.9%, 3.5%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.5% (95% CI 1.2%, 1.9%), 1.5% in the Caucasians (95% CI 1.1%, 1.9%) and 2.0% in the African Americans (95% CI 1.1%, 3.7%). The overall prevalence of CYP2C19 poor metabolizers was 2.0% (95% CI 1.8%, 2.7%), 2.2% in Caucasians (95% CI 1.6%, 2.5%) and 4.0% in African Americans (95% CI 2.6%, 6.1%). CONCLUSION: We also propose a numeric system for expression of CYP2D6 and CYP2C19 enzyme activity to aid clinicians in determining treatment strategy for patients receiving therapeutics that are metabolized by the CYP2D6 or CYP2C19 gene products.