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Ancient Genetic Signatures of Orang Asli Revealed by Killer Immunoglobulin-Like Receptor Gene Polymorphisms.

ABSTRACT: The aboriginal populations of Peninsular Malaysia, also known as Orang Asli (OA), comprise three major groups; Semang, Senoi and Proto-Malays. Here, we analyzed for the first time KIR gene polymorphisms for 167 OA individuals, including those from four smallest OA subgroups (Che Wong, Orang Kanaq, Lanoh and Kensiu) using polymerase chain reaction-sequence specific primer (PCR-SSP) analyses. The observed distribution of KIR profiles of OA is heterogenous; Haplotype B is the most frequent in the Semang subgroups (especially Batek) while Haplotype A is the most common type in the Senoi. The Semang subgroups were clustered together with the Africans, Indians, Papuans and Australian Aborigines in a principal component analysis (PCA) plot and shared many common genotypes (AB6, BB71, BB73 and BB159) observed in these other populations. Given that these populations also display high frequencies of Haplotype B, it is interesting to speculate that Haplotype B may be generally more frequent in ancient populations. In contrast, the two Senoi subgroups, Che Wong and Semai are displaced toward Southeast Asian and African populations in the PCA scatter plot, respectively. Orang Kanaq, the smallest and the most endangered of all OA subgroups, has lost some degree of genetic variation, as shown by their relatively high frequency of the AB2 genotype (0.73) and a total absence of KIR2DL2 and KIR2DS2 genes. Orang Kanaq tradition that strictly prohibits intermarriage with outsiders seems to have posed a serious threat to their survival. This present survey is a demonstration of the value of KIR polymorphisms in elucidating genetic relationships among human populations.

SUBMITTER: NurWaliyuddin HZ

PROVIDER: S-EPMC4643969 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionNon-communicable disease (NCD) risk is influenced by environmental factors that are highly variable worldwide, yet prior research has focused mainly on high-income countries where most people are exposed to relatively homogeneous and static environments. Understanding the scope and complexity of environmental influences on NCD risk around the globe requires more data from people living in diverse and changing environments. Our project will investigate the prevalence and environmental causes of NCDs among the indigenous peoples of Peninsular Malaysia, known collectively as the Orang Asli, who are currently undergoing varying degrees of lifestyle and sociocultural changes that are predicted to increase vulnerability to NCDs, particularly metabolic disorders and musculoskeletal degenerative diseases.Methods and analysisBiospecimen sampling and screening for a suite of NCDs (eg, cardiovascular disease, type II diabetes, osteoarthritis and osteoporosis), combined with detailed ethnographic work to assess key lifestyle and sociocultural variables (eg, diet, physical activity and wealth), will take place in Orang Asli communities spanning a gradient from remote, traditional villages to acculturated, market-integrated urban areas. Analyses will first test for relationships between environmental variables, NCD risk factors and NCD occurrence to investigate how environmental changes are affecting NCD susceptibility among the Orang Asli. Second, we will examine potential molecular and physiological mechanisms (eg, epigenetics and systemic inflammation) that mediate environmental effects on health. Third, we will identify intrinsic (eg, age and sex) and extrinsic (eg, early-life experiences) factors that predispose certain people to NCDs in the face of environmental change to better understand which Orang Asli are at greatest risk of NCDs.Ethics and disseminationApproval was obtained from multiple ethical review boards including the Malaysian Ministry of Health. This study follows established principles for ethical biomedical research among vulnerable indigenous communities, including fostering collaboration, building cultural competency, enhancing transparency, supporting capacity building and disseminating research findings.

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Ancient Genetic Signatures of Orang Asli Revealed by Killer Immunoglobulin-Like Receptor Gene Polymorphisms.

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