Genotyping by Mass Spectrometry

Abstract

Important progress in disease genetics has been made during the last decade in identifying genes and mutations responsible for the heritable basis of numerous rare Mendelian disorders. The tools devised that have made this progress possible are now being refined, modified, extended and adapted to address the major challenge of the next decade: identification of the sequence variation that determines susceptibility to common, genetically complex disorders. Since these diseases are common they contribute much more to the burden of disease that afflicts contemporary human societies than do rare Mendelian disorders. This prevalence suggests that the alleles responsible for susceptibility may also be prevalent. Such alleles are possibly variant alleles that have been selectively neutral through most of the approximately 150,000 year history of modern humans and have been globally dispersed with human colonization of the planet. Susceptibility alleles do not independently confer disease: they require specific environments to manifest deleterious effects. Such environmental factors may have been absent prior to the emergence of industrialized societies. This paradigm explains why these diseases and their susceptibility alleles have become geographically widespread (1,2). A competing hypothesis is that common genetic diseases result from recent mutations that have not yet been subject to the effects of purifying selection (3).