Rapid technological progress in determining genomic sequences from multiple individuals has made it possible to collect vast quantities of single nucleotide polymorphism (SNP) data. The ability to generate this SNP data has fueled interest in the characterization and application of population genetic analyses to this form of intraspecific genetic variation. While a thorough collection of human SNPs is considered vital to future progress determining the genetic basis of complex traits or diseases, the great challenge that awaits is to determine the functional consequences associated with genomic SNPs. This proposal first aims to identify human genomic SNPs in forty randomly selected genomic regions from a well defined set of forty individual genomic DNA samples. Discovered SNPs will then be genotyped in 40 samples from each of four distinct human populations. Indirect population genetic methods will then be employed to identify regions that depart from infinite site neutral theory expectations because of the action of natural selection. Natural selection is expected to perturb extant patterns of intraspecific SNP variation in genomic regions in predictable ways. Because natural selection can operate on extraordinarily subtle phenotypic differences that may not be directly measureable in a typical laboratory experiment, the ability to detect the action of selection in a genomic region may significantly aid in the identification of the genetic variants underlying complex human traits or diseases.
