Genomic Variation in Human Disease
Genetic and functional analysis of single gene (Mendelian) diseases have shown that the underlying mutations are necessary and sufficient for the trait, generally rare in human populations and of recent origin. In contrast, the genetic basis of complex diseases are expected to lie in mutations which are neither necessary nor sufficient for the trait, as common in human populations and can have great antiquity. Whether this apparent dichotomy in the nature of genetic variation which underlies human traits is true or not remains to be elucidated. If susceptibility gene variants are common, then genetic analysis of common chronic diseases can benefit from population-based and family-based association studies. The current interest in a catalog of common human single nucleotide polymorphisms (SNPs) is based on this reasoning. I will discuss how recognition of patterns of genomic sequence variation is contributing to future studies of the molecular basis of common disorders.
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University