ABSTRACT
Figure 2. Discovery of functional genome maintenance variants in human longevity. A hierarchical, multidisciplinary approach will increase the chances of identifying functional variations in the genome maintenance genes that influence human longevity. Genetic association in case/control studies establishes genetic link between genome maintenance genes and human longevity. Controls are typically elderly individuals and cases are extremely longlived individuals, such as centenarians. Genetic association established by common marker variants requires resequencing analysis to identify potentially functional variants, whereas direct resequencing of candidate genes leads to discovery of such variants. Individually rare longevity-associated variants may be enriched in cases as a group as compared to controls. In silico analysis predicts the outcomes of potentially functional variants and helps prioritize candidate variants for further functional analysis. Integrated multiple in vitro and in vivo assays are needed to assess the functional roles of each longevity-associated genome maintenance gene variants depending upon the nature and location of gene variants.
