VARIATION AND LINKAGE DISEQUILIBRIUM IN THE HUMAN GENOME

University Of Chicago, Chicago IL

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Abstract

Understanding human genetic variation and the forces which affect this variation are crucial for elucidating the genetic basis of complex phenotypes. Linkage disequilibrium (LD) methods have been proposed for mapping these complex phenotypes to particular loci. However to use LD, an understanding of the genome wide effects of LD are needed. Demography is one of the main determinants of genetic variation under neutral models of evolution. This proposal will directly evaluate sequence variation and LD at 10 sets of independent regions in order to discriminate between demographic scenarios. In order to study the effects of demography, genomic regions will be chosen that are unlikely to be of functional importance or under selective pressure. A 10 kb segment of each region will be amplified and 1-2kb at each end of the segment by sequencing. Analysis will be focused on estimating the effect of population growth on the patterns of sequence variation and LD for a variety of models using both analytical methods and computer simulations. Once demographic parameters have been estimated from empirical evidence, a detailed characterization of the expected variability of these quantities can be obtained across the genome.