Prof Felix Jin Li

Title: Identification of copy number variation hotspots in human populations

Copy number variants (CNVs) in the human genome contribute to both Mendelian and complex traits as well as genomic plasticity in evolution. Much progress was made to unravel the CNV formation mechanisms; however, the evaluation of CNV mutation rate at genome level poses an insurmountable practical challenge. We showed that an approximate estimation of CNV mutation rate could be achieved using the phylogeny information of flanking SNPs. This allows a genome-wide comparison of mutation rates between CNVs for identifying mutational hotspots using HapMap genotyping data. The mutation rates for the majority of 4,330 CNVs investigated in this study are at the order of 10-5 per generation, consistent with experimental observations at individual loci. Notably, the mutation rates of 132 (3.0%) CNVs are at the order of 10-3 per generation, therefore, identified as hotspots. Further analyses revealed that genome architecture has a potential role in inciting mutational hotspots in the human genome.