Genetic Investigation of an Iranian Supercentenarian by Whole Exome Sequencing.

Abstract

The genetic basis of longevity is an important field of study because the majority of supercentenarian cases experience healthy aging and may only show age-related diseases in their last few years of life. It is clear that genetic factors play an important role in survival beyond 90 years of age, but the exact relationship of genetic variants to this phenomenon remains unknown. The aim of this project was to investigate different hypotheses that describe the relationship between genetic variants and human longevity in a living Iranian man by Whole Exome Sequencing. Initially, we conducted high quality DNA extraction on a peripheral blood sample. Then, whole exome sequencing was performed on the DNA and different bioinformatic software packages and databases were used to analyze the data. Tertiary analysis was performed on four genetic hypotheses for longevity. Analysis showed that among 27 metabolic variants which are related to longevity, 18 variants encompassed the exceptional longevity allele. In comparison with the NHGRI GWAS catalog, the case had 58 trait-associated variants of which 11 were homozygous for the risk allele. We also discovered 25 novel variants within candidate genes for aging and longevity and we detected seven longevity-associated variants in the sample. This study was performed on just one sample and so the results cannot be interpreted as a generalized principle for other elderly societies, but this is the first step towards investigation of the genetic basis of longevity in Iran and provides an insight for further studies in the field of longevity.