title: Copy number polymorphisms in new HapMap III and Singapore populations.
abstract: Copy number variations can be identified using newer genotyping arrays with higher single nucleotide polymorphisms (SNPs) density and copy number probes accompanied by newer algorithms. McCarroll et al. (2008) applied these to the HapMap II samples and identified 1316 copy number polymorphisms (CNPs). In our study, we applied the same approach to 859 samples from three Singapore populations and seven HapMap III populations. Approximately 50% of the 1291 autosomal CNPs were found to be polymorphic only in populations of non-African ancestry. Pairwise comparisons among the 10 populations showed substantial differences in the CNPs frequencies. Additionally, 698 CNPs showed significant differences with false discovery rate (FDR)<0.01 among the 10 populations and these loci overlap with known disease-associated or pharmacogenetic-related genes such as CFHR3 and CFHR1 (age related macular degeneration), GSTTI (metabolism of various carcinogenic compounds and cancers) and UGT2B17 (prostate cancer and graft-versus-host disease). The correlations between CNPs and genome-wide association studies-SNPs were investigated and several loci, which were previously unreported, that may potentially be implicated in complex diseases and traits were found; for example, childhood acute lymphoblastic leukaemia, age-related macular degeneration, breast cancer, response to antipsychotic treatment, rheumatoid arthritis and type-1 diabetes. Additionally, we also found 5014 novel copy number loci that have not been reported previously by McCarroll et al. (2008) in the 10 populations.
authors.affiliation: Centre for Molecular Epidemiology, Department of Epidemiology and Public Health (MD3), Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore. g0700040@nus.edu.sg
authors.forename: Chee-Seng
authors.initials: CS
authors.lastname: Ku
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Teo
authors.forename: Nasheen
authors.initials: N
authors.lastname: Naidoo
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
authors.forename: Yudi
authors.initials: Y
authors.lastname: Pawitan
authors.forename: Mark
authors.initials: M
authors.lastname: Seielstad
authors.forename: Kee-Seng
authors.initials: KS
authors.lastname: Chia
authors.forename: Agus
authors.initials: A
authors.lastname: Salim
mesh_terms: D001798:Blood Proteins / Q000235:genetics; D002681:China / Q000208:ethnology; D003180:Complement C3b Inactivator Proteins / Q000235:genetics; D056915:DNA Copy Number Variations; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005828:Genetics, Population; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D060148:HapMap Project; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007194:India / Q000208:ethnology; D008296:Malaysia / Q000208:ethnology; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012846:Singapore
chemical_list: D001798:Blood Proteins; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins; D015778:Minor Histocompatibility Antigens; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase