Abiotrophic gene action in Homo sapiens: potential mechanisms and significance for the pathobiology of aging

Abstract

A subset of genetic loci of Homo sapiens are reviewed that: 1) have the potential for allelic variation (either mutation or polymorphism) such that degenerative and/or proliferative phenotypic aberrations may be of relatively late onset ('abiotrophic'); 2) have phenotypic features which overlap, to some extent, with those of important age-related disorders of man (many of which are systematically tabulated in this review); 3) have had significant characterization at the biochemical genetic level. The ascertainment bias of physicians to discover strong phenotypic effects ('non-leaky' mutations) obscures the fact that, for many such instances, there exist numerous other alleles of lesser effects, including those whose gene actions probably escape the force of natural selection. The patterns of 'normal' aging in Homo sapiens are quite variable and, hence, difficult to define. It seems likely that the 'wild-type' alleles of a number of loci will also be found to have antagonistic pleiotropic effects that contribute to the syndromology of senescence in our species.