title: Novel population specific autosomal copy number variation and its functional analysis amongst Negritos from Peninsular Malaysia.
abstract: Copy number variation (CNV) has been recognized as a major contributor to human genome diversity. It plays an important role in determining phenotypes and has been associated with a number of common and complex diseases. However CNV data from diverse populations is still limited. Here we report the first investigation of CNV in the indigenous populations from Peninsular Malaysia. We genotyped 34 Negrito genomes from Peninsular Malaysia using the Affymetrix SNP 6.0 microarray and identified 48 putative novel CNVs, consisting of 24 gains and 24 losses, of which 5 were identified in at least 2 unrelated samples. These CNVs appear unique to the Negrito population and were absent in the DGV, HapMap3 and Singapore Genome Variation Project (SGVP) datasets. Analysis of gene ontology revealed that genes within these CNVs were enriched in the immune system (GO:0002376), response to stimulus mechanisms (GO:0050896), the metabolic pathways (GO:0001852), as well as regulation of transcription (GO:0006355). Copy number gains in CNV regions (CNVRs) enriched with genes were significantly higher than the losses (P value <0.001). In view of the small population size, relative isolation and semi-nomadic lifestyles of this community, we speculate that these CNVs may be attributed to recent local adaptation of Negritos from Peninsular Malaysia.
authors: Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.
authors: Siti Shuhada
authors: SS
authors: Mokhtar
authors: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada; McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors: Christian R
authors: CR
authors: Marshall
authors: Jeffrey Cheah School of Medicine and Health Sciences, Monash University Sunway Campus, Selangor, Malaysia.
authors: Maude E
authors: ME
authors: Phipps
authors: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Bhooma
authors: B
authors: Thiruvahindrapuram
authors: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Anath C
authors: AC
authors: Lionel
authors: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada; McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors: Stephen W
authors: SW
authors: Scherer
authors: Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.
authors: Hoh Boon
authors: HB
authors: Peng
mesh_terms: D000222:Adaptation, Physiological; D000293:Adolescent; D025063:Chromosome Disorders / Q000208:ethnology / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D063990:Gene Ontology; D014644:Genetic Variation; D005828:Genetics, Population; D015894:Genome, Human / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008296:Malaysia; D008297:Male; D012641:Selection, Genetic