Single nucleotide polymorphisms in human health and disease: Towards resolution of a conundrum

Abstract

Single nucleotide polymorphisms, also referred to as Single nucleotide variants remain single most dominant feature of variations in the human genome. The large numbers, stability and presence at easily detectable frequencies make them the most suitable potential markers for association studies in human health and disease. The study of these common genetic variants has now evolved and given rise to the understanding of less frequently encountered ‘rare’ variants of varying minor allele frequencies. The acceptance of role of rare single nucleotide variants in human diseases appears to coincide with the phasing out of the term ‘mutation’ in the dbSNP. The contribution of rare variants helps resolve the enigma of heritability of complex traits to a great extent. Integration of analysis of rare and common variants with the support of technological innovations and improved strategies for data analyses is expected to yield better and reliable association data. By virtue of their relatively stronger impact on the phenotype compared to that of the common variants, rare variants are likely to be better candidates as markers of association as well as targets for intervention strategies while providing mechanistic insights into the underlying biological processes. Starting with discussion of the basics of single nucleotide variants, this review summarizes concepts and principles of approaches used to study their association with parameters in health and diseases including cancer. Implications for studies in Indian population are discussed.