SNP and haplotype variation in the human genome.

We have surveyed and summarized several aspects of DNA variability among humans. The variation described is the result of mutation followed by a combination of drift, migration and selection bringing the frequencies high enough to be observed. This paper describes what we have learned about how DNA variability differs among genes and populations. We sequenced functional regions of a set of 3950 genes. DNA was sampled from 82 unrelated humans: 20 African-Americans, 20 East Asians, 21 Caucasians, 18 Hispanic-Latinos and 3 Native Americans. Different aspects of variability showed a great deal of concordance. In particular, we studied patterns of single nucleotide polymorphism (SNP) allele and haplotype sharing among the four, large sample populations. We also examined how linkage disequilibrium (LD) between SNPs relates to physical distance in the different populations. It is clear from our findings that while many variants are common to all populations, many others have a more restricted distribution. Research that attempts to find genetic variants that explain phenotypic variants must be careful in their choice of study population.

DNA variability of human genes.

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.