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LINKAGE INFORMATION CONTENT FOR POLYMORPHIC GENETIC MARKERS

$15,016P41FY2000RRNIH

Case Western Reserve University, Cleveland OH

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Abstract

In recent years, there has been a focus on methods to understand the etiology of complex disorders which do not follow simple Mendelian, single locus segregation. Some of these methods make use of components of genetic variance. After giving simple general formulations to derive all the components of total genetic variance for multilocus models, we investigated these components for a series of fifteen two-allele two-locus disease models with incomplete penetrance. We discussed the restrictions and limitations implied by the disease prevalence on both these components and the gene frequencies. Finally, we investigated the relative magnitudes of the components of variance for the various models when penetrance is complete. It is found that the epistatic components of variance are non-trivial, relative to the other components of variance, in seven of the models studied. These models may be of special interest for the study of complex diseases in which the recurrence among relatives beyond first degree decreases sharply.

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