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Predictions of a2‐locus model fordiseaseheterogeneity:Application toadrenoleukodystrophy Nancy E. MaestriTerri H. Beaty1992 год

Predictions of a 2‐locus model for disease heterogeneity: Application to adrenoleukodystrophy
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Аннотация: Abstract Adrenoleukodystrophy (ALD) is an X‐linked disorder that exhibits a wide range of phenotypic variability within individuals in a single family carrying the mutant allele. A 2‐locus epistatic model has been proposed to explain the inheritance of the severe childhood form of ALD and the milder adult‐onset adrenomyloneuropathy (AMN). Under a dominant epistatic model, a single M allele at an autosomal modifier locus ameliorates the most severe effects of the disease allele leading to the milder AMN phenotype; only males with genotype mm would have ALD. Under a recessive epistatic model, 2 copies of the M allele would be necessary to have the milder AMN phenotype. Here, we show that recurrence risks for a second affected male depend on the frequency of the protective allele at this modifier locus. Whereas it is most likely that 2 affected brothers will be concordant for their disease phenotypes, discordant pairs of affected brothers are possible at all frequencies of M . Within a narrow range of modifier allele frequencies, the predicted distribution of affected sib pairs (over all families) is consistent with empiric data from a large clinic population. Here we suggest sampling discordant affected sib pairs as a strategy for detecting linkage between a polymorphic DNA marker and a possible modifier gene. Since both epistatic models predict that discordant affected pairs should not share 2 alleles at the modifier locus, we expect that departures from the null distribution could be detected with relatively small numbers of sib pairs. © 1992 Wiley‐Liss, Inc.
Год издания: 1992
Авторы: Nancy E. Maestri, Terri H. Beaty
Издательство: Wiley
Источник: American Journal of Medical Genetics
Ключевые слова: Peroxisome Proliferator-Activated Receptors, Nitric Oxide and Endothelin Effects, Adipose Tissue and Metabolism
Другие ссылки: American Journal of Medical Genetics (HTML)
PubMed (HTML)