DNA variability of human genes

Abstract We have investigated the level of DNA-based variation (both SNPs and haplotypes) for several thousand human genes. In addition, we have characterized how this variation is distributed in a number of biologically and clinically important ways. First, we have determined how SNPs are distributed within human genes: where they occur relative to various functional regions; levels of variability of human SNPs; pattern of the molecular sequence of SNPs; and how these compare with the corresponding sequence of a chimpanzee. Second, we have determined how these aspects of SNP distribution vary among four human population samples. All genes were sequenced on DNA obtained from 82 unrelated individuals: 20 African–Americans, 20 East Asians, 21 European–Americans, 18 Hispanic–Latinos and three Native Americans. In particular, we looked at patterns of SNP and haplotype sharing among the four larger population samples. Third, we have determined the patterns of linkage disequilibrium among SNPs, which also determines the haplotype variability of each gene. These characteristics also vary substantially among populations. A deeper understanding of these aspects of human genetic variation will be of vital importance when trying to identify the genetic contribution to complex phenotypes such as aging.