Abstract
Historically genotypic variation has been detected at the phenotypic level, at the metabolic level, and at the protein chemistry level. Advances in technology have allowed its direct visualisation at the level of DNA variation. Nevertheless, there is still an enormous interest in phenotypic, metabolic and protein property variability, since such variation gives insights into potential functionally important differences conferred by genetic variation. High-throughput transcriptomics and proteomics applied to different individuals drawn from a population has the potential to identify the functional consequences of genetic variability, in terms of either differences in expression of mRNA or in terms of differences in the quantities, pI(s) or molecular weight(s) of an expressed protein. Family studies can define the genetic component of such variation (segregation analysis) and with the genotyping of well-spaced markers can map the causative factors to broad chromosomal regions (linkage analysis). Association studies in the variant proteins have the greatest power to confirm the presence of cis-acting genetic variants. The most powerful study designs may combine elements of both family and association studies applied to proteomic and transcriptomic analyses. Such studies may provide appreciable advances in our understanding of the genetic aetiology of complex disorders.