DETERMINATION OF COPY NUMBER VARIATION IN SINGAPORE POPULATIONS AND ITS APPLICATION TO POPULATION GENETICS AND BIOLOGICAL TRAITS

Abstract

Copy number or structural variation contributes to human genetic diversity, disease susceptibility and evolution, and elucidating their role requires understanding the distribution of CNV polymorphisms. This study of 3 populations (Chinese, Malays, Indians in Singapore) has established a CNV catalogue, including frequency, type, and loci. Quantitative PCR was used to validate array hybridization-based genotypes. The natural selection of population-specific and population-differentiated CNVs was explored. The Amylase genes were studied as examples of multiallelic CNV. We developed an improved method of genotyping copy numbers by qPCR and digital PCR, allowing discovery of a novel distribution pattern of AMY1 diploid copy number with even:odd genotype imbalance, due to underlying haplotype structures. Using the improved method we found no association of AMY1 or AMY2A copy numbers with obesity, despite a previous report. This work highlights the technical challenges faced in the field, and demonstrates feasible solutions to genotype multiallelic CNV.