THEORETICAL METHODS FOR STUDYING HAPLOTYPES

Yale University, New Haven CT

Investigators

Linked publications & trials

Abstract

A complex of forces determines the extent of linkage disequilibrium among a set of loci in a given population. As a general rule, the magnitude of disequilibrium between a pair of loci decays systematically in each generation due to recombination. However, the amount of disequilibrium at the founding of the population depends on numerous systematic and random factors. In this proposal, we focus on developing and applying methods to measure the degree of association among a set of linked loci. These measures will then be contrasted across chromosomal regions which are presumed to have different physical distance/recombination fraction relationship, as well as across populations with different histologies. These methods will be based on linear regression and nested analysis of variance. We intend to initially concentrate on pair wise measures of disequilibrium. With pair wise measures considered on all pairs of a set of linked loci, disequilibrium estimates are correlated, and we intend to evaluate the effect of this correlation. The methods that we develop will be tested using simulation programs that generate population haplotype data for a set of linked marker loci. These programs will also allow us to evaluate the effect of various biological/demographic forces, such as mutation at marker loci, gene flow, and genetic drift. Finally, these methods will be applied to the data collected in Projects 1, 2 and 3 by Drs. Kidd, Kidd and Ward. Given our experience from the simulation studies, we hope to understand the linkage disequilibrium relationships established in these projects.