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

Mokhtar SS, Marshall CR, Phipps ME, Thiruvahindrapuram B, Lionel AC, Scherer SW, Peng HB - PLoS ONE (2014)

Bottom Line: It plays an important role in determining phenotypes and has been associated with a number of common and complex diseases.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, 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.

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Gene Ontology and pathway analyses on the gene set within the Negrito-specific CNVs using PANTHER and DAVID.(a) PANTHER analysis suggests a major involvement of the genes harboring the population specific CNVs in the immune system process and response to stimulus, as well as the metabolic process; (b) DAVID analysis suggests the involvement of the genes harboring the population specific CNVs in the transcription and regulation of RNA metabolic processes.
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pone-0100371-g005: Gene Ontology and pathway analyses on the gene set within the Negrito-specific CNVs using PANTHER and DAVID.(a) PANTHER analysis suggests a major involvement of the genes harboring the population specific CNVs in the immune system process and response to stimulus, as well as the metabolic process; (b) DAVID analysis suggests the involvement of the genes harboring the population specific CNVs in the transcription and regulation of RNA metabolic processes.

Mentions: To understand the putative functional implications of these CNVs, we performed the Gene Ontology (GO) and pathway analyses on the gene set within the Negrito-specific CNVs using PANTHER and DAVID (Figure 5). Of the 48 CNVs specific to Negritos, 29 carried annotated genes while the remaining were gene-poor regions (Table 4). For all the CNVRs enriched with genes, copy number gains were significantly higher than the losses (15 gain versus 6 losses) (P<0.001). GO analysis by PANTHER revealed fourteen genes involved in immune system function and regulation, response to stimulus and metabolic pathways; whereas DAVID revealed that transcription regulation, and regulation of RNA metabolic processes to be the most significant GO term. The list of genes involved in the major biological processes is listed in Table 5.


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

Mokhtar SS, Marshall CR, Phipps ME, Thiruvahindrapuram B, Lionel AC, Scherer SW, Peng HB - PLoS ONE (2014)

Gene Ontology and pathway analyses on the gene set within the Negrito-specific CNVs using PANTHER and DAVID.(a) PANTHER analysis suggests a major involvement of the genes harboring the population specific CNVs in the immune system process and response to stimulus, as well as the metabolic process; (b) DAVID analysis suggests the involvement of the genes harboring the population specific CNVs in the transcription and regulation of RNA metabolic processes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4067311&req=5

pone-0100371-g005: Gene Ontology and pathway analyses on the gene set within the Negrito-specific CNVs using PANTHER and DAVID.(a) PANTHER analysis suggests a major involvement of the genes harboring the population specific CNVs in the immune system process and response to stimulus, as well as the metabolic process; (b) DAVID analysis suggests the involvement of the genes harboring the population specific CNVs in the transcription and regulation of RNA metabolic processes.
Mentions: To understand the putative functional implications of these CNVs, we performed the Gene Ontology (GO) and pathway analyses on the gene set within the Negrito-specific CNVs using PANTHER and DAVID (Figure 5). Of the 48 CNVs specific to Negritos, 29 carried annotated genes while the remaining were gene-poor regions (Table 4). For all the CNVRs enriched with genes, copy number gains were significantly higher than the losses (15 gain versus 6 losses) (P<0.001). GO analysis by PANTHER revealed fourteen genes involved in immune system function and regulation, response to stimulus and metabolic pathways; whereas DAVID revealed that transcription regulation, and regulation of RNA metabolic processes to be the most significant GO term. The list of genes involved in the major biological processes is listed in Table 5.

Bottom Line: It plays an important role in determining phenotypes and has been associated with a number of common and complex diseases.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, 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.

Show MeSH