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.
The endothelium plays a crucial role in maintaining vascular homeostasis by producing several vasodilating factors, including nitric oxide (NO), prostacyclin (PGI2), and endothelium-dependent hyperpolarisation (EDH); however, the balance between endothelial relaxing and contracting factors is disrupted in disease states such as diabetes mellitus and hypertension. Most reported studies of endothelial dysfunction in diabetes focused on the actions of NO; however, there is accumulating evidence demonstrating that in addition to NO, PGI2 and EDH are likely to contribute to the vasodilatation of blood vessels. EDH plays an important role as a regulator of vascular tone and reactivity in resistance and conduit arteries of animal models and humans. PGI2 only plays a minimal role in endothelium-dependent vasodilatation but may serve as an important compensatory mechanism in conditions in which NO and EDH activities are decreased. Further studies are needed to determine the exact roles of EDH and PGI2 in the development of endothelial dysfunction and clinical vasculopathy in humans with type 1 and type 2 diabetes.