A population-based study of copy number variations and regions of homozygosity in Singapore and Swedish populations using genome-wide SNP genotyping arrays

Abstract

Population-based studies of copy number variations (CNVs) and regions of homozygosity (ROHs) have received considerable attention over the past few years. In addition, CNVs and ROHs were also found to be associated with various human complex diseases and traits such as schizophrenia, autism and height. Genome-wide mapping of CNVs and ROHs have been previously performed in European, East Asian and African populations using high-density SNP genotyping arrays. However, a comprehensive mapping study of CNVs and ROHs in the Singapore and Swedish populations has not been conducted previously. Therefore, the primary aim of this thesis was to detect and describe the characteristics of CNVs and ROHs in these two populations. A total of 292 samples from three Singaporean populations (99 Chinese, 98 Malay, and 95 Indian individuals) and 100 samples from the Swedish population were genotyped using the Affymetrix Genome-Wide Human SNP Array 6.0 or/and Illumina Human1M BeadChip arrays. Subsequently, several hundred CNV loci and ROH loci were found in both populations. More interestingly, some of these CNV loci overlapped with known disease associated or pharmacogenetic-related genes and showed substantial population frequency differences. Novel CNV loci that were not previously reported in public databases were also identified. Comparisons between these two populations and with the International HapMap III populations found substantial differences in their CNV and ROH profiles. Collectively, these results highlight the importance of characterizing CNVs and ROHs in individual populations. The studies in this thesis will establish a resource of CNVs and ROHs for future disease association studies in the Singapore and Swedish populations.