The influence of short indel heterozygosity on local nucleotide mutation rate

University Of Florida, Gainesville FL

Investigators

Abstract

All organisms' genomes mutate, but do some mutate more than others? For example, are individuals with differing lengths of repetitive DNA at a given site in their genome more likely to mutate? To examine this question, next-generation DNA sequencing technology will be used to compare the mutational properties at genomic sites that differ in length in 16 individuals from an experimental population of nematode worms. The DNA sequencing information will be used to test whether 1) sites that differ by short stretches of DNA mutate more than sites that do not and 2) if there is a greater number of single DNA base mutations in the regions flanking the sites that differ in length. Understanding how differences in mutational properties differ between and within species has implications beyond pure academic interests. Most people who live in an industrialized society will die of diseases with a complex genetic basis; for example, there are a multitude of subtle genetic causes that lead to cancers. If genomic mutation rates differ significantly among individuals within a species, this would have a significant effect on how to best approach the study of such complex diseases. In particular, the understanding of the "rare variant/common variant" conceptual framework that motivates association studies of human diseases would need to be re-evaluated in light of a greater appreciation of the role of rare variants in the human population. If individuals with differing lengths of repetitive DNA at a given site are predisposed to mutation, this will indeed be the case.