Final Report - DE-FG03-97ER62385

OAK B188 Single nucleotide polymorphism (SNPs) are the most common form of sequence variation in the human genome, and based on their natural frequency, they are also likely to be the underlying cause of most phenotypic differences in humans. Since SNPs are found in both coding and non-coding regions of the genome, randomly distributed markers as well as markers clustered in genes can be discovered. The majority of SNPs found in coding regions (cSNPs) are single base substitutions that may or may not lead to amino acid substitutions. Some cSNPs can result in changes in the activity of protein by altering a functionally important amino acid residue(s), and these are of interest for their potential links with phenotype, e.g. disease susceptibility or resistance. Other cSNPs (synonymous and non-synonymous) may prove useful for their potential links to functional cSNPs via linkage disequilibrium mapping. With funding from the Department of Energy, we have explored approaches: (1) to improve technology to find SNPs in the human genome using fluorescence-based sequencing, and (2) to mine SNPs from genome resources such as expressed-sequence tag (EST) sequences