Novel population specific autosomal copy number variation and its functional analysis amongst Negritos from Peninsular Malaysia

Siti Shuhada Mokhtar; Christian R Marshall; Maude E Phipps; Bhooma Thiruvahindrapuram; Anath C Lionel; Stephen W Scherer; Hoh Boon Peng

doi:10.1371/journal.pone.0100371

Novel population specific autosomal copy number variation and its functional analysis amongst Negritos from Peninsular Malaysia

PLoS One. 2014 Jun 23;9(6):e100371. doi: 10.1371/journal.pone.0100371. eCollection 2014.

Authors

Siti Shuhada Mokhtar¹, Christian R Marshall², Maude E Phipps³, Bhooma Thiruvahindrapuram⁴, Anath C Lionel⁴, Stephen W Scherer², Hoh Boon Peng¹

Affiliations

¹ Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.
² 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.
³ Jeffrey Cheah School of Medicine and Health Sciences, Monash University Sunway Campus, Selangor, Malaysia.
⁴ The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptation, Physiological
Adolescent
Chromosome Disorders / ethnology
Chromosome Disorders / genetics*
DNA Copy Number Variations / genetics*
Female
Gene Ontology
Genetic Variation*
Genetics, Population*
Genome, Human / genetics*
Genotype
Humans
Malaysia
Male
Selection, Genetic*

Grants and funding

This study is supported by Ministry of Science, Technology and Innovation (MOSTI) grant erBiotek Grant # 100-RM/BIOTEK 16/6/2 B (1/2011) and [100-RMI/GOV 16/6/2 (19/2011] awarded to HB Peng & ME Phipps, Dr. Ranjeet Bhagwan Singh International Fellowship (Academy of Science Malaysia) awarded to HB Peng and support from the University of Toronto McLaughlin Centre and The Hospital for Sick Children Foundation. ACL holds a NeuroDevNet doctoral fellowship. SWS holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.