Understanding the Functional Importance of Human Single Nucleotide Polymorphisms

Abstract

Single nucleotide polymorphisms (SNPs) are the major source of human genetic variation, and the functional subset of SNPs, predominantly in protein coding regions, contributes to phenotypic variation. However, much of the variation in coding regions may not produce any functional effects. There are two broad strategies for classifying polymorphism as functional or neutral: sequence-based methods predict functional significance based on conservation scores calculated from alignments of homologous gene sequences; structure-based methods map variations to known protein structures and predict likely effects based on properties of proteins. Several tools have been developed to classify polymorphism as functional or neutral based on these methods. It was shown that most of functional SNPs are evolutionarily deleterious. Though the utility of the tools has not yet been adequately demonstrated, they may have important applications in the area of medical genetics.