Admixture Patterns and Genetic Differentiation in Negrito Groups from West Malaysia Estimated from Genome-wide SNP Data

Southeast Asia houses various culturally and linguistically diverse ethnic groups. In Malaysia, where the Malay, Chinese, and Indian ethnic groups form the majority, there exist minority groups such as the negritos who are believed to be descendants of the earliest settlers of Southeast Asia. Here we report patterns of genetic substructure and admixture in two Malaysian negrito populations (Jehai and Kensiu), using ~50,000 genome-wide single-nucleotide polymorphism (SNP) data. We found traces of recent admixture in both the negrito populations, particularly in the Jehai, with the Malay through principal component analysis and STRUCTURE analysis software, which suggested that the admixture was as recent as one generation ago. We also identified significantly differentiated nonsynonymous SNPs and haplotype blocks related to intracellular transport, metabolic processes, and detection of stimulus. These results highlight the different levels of admixture experienced by the two Malaysian negritos. Delineating admixture and differentiated genomic regions should be of importance in designing and interpretation of molecular anthropology and disease association studies

Genetic evidence supports linguistic affinity of Mlabri - a hunter-gatherer group in Thailand

<p>Abstract</p> <p>Background</p> <p>The Mlabri are a group of nomadic hunter-gatherers inhabiting the rural highlands of Thailand. Little is known about the origins of the Mlabri and linguistic evidence suggests that the present-day Mlabri language most likely arose from Tin, a Khmuic language in the Austro-Asiatic language family. This study aims to examine whether the genetic affinity of the Mlabri is consistent with this linguistic relationship, and to further explore the origins of this enigmatic population.</p> <p>Results</p> <p>We conducted a genome-wide analysis of genetic variation using more than fifty thousand single nucleotide polymorphisms (SNPs) typed in thirteen population samples from Thailand, including the Mlabri, Htin and neighboring populations of the Northern Highlands, speaking Austro-Asiatic, Tai-Kadai and Hmong-Mien languages. The Mlabri population showed higher LD and lower haplotype diversity when compared with its neighboring populations. Both model-free and Bayesian model-based clustering analyses indicated a close genetic relationship between the Mlabri and the Htin, a group speaking a Tin language.</p> <p>Conclusion</p> <p>Our results strongly suggested that the Mlabri share more recent common ancestry with the Htin. We thus provided, to our knowledge, the first genetic evidence that supports the linguistic affinity of Mlabri, and this association between linguistic and genetic classifications could reflect the same past population processes.</p

Gene-centric meta-analyses of 108,912 individuals confirm known body mass index loci and reveal three novel signals

Recent genetic association studies have made progress in uncovering components of the genetic architecture of body mass index (BMI). We used the ITMAT-Broad-CARe (IBC) array comprising up to 49,320 single nucleotide polymorphisms (SNPs) across ~2,100 metabolic and cardiovascular-related loci to genotype up to 108,912 individuals of European ancestry (EA), African Americans, Hispanics, and East Asians, from 46 studies, to provide additional insight into SNPs underpinning BMI. We used a five-phase study design: Phase I focused on meta-analysis of EA studies providing individual level genotype data; Phase II performed a replication of cohorts providing summary level EA data; Phase III meta-analyzed results from the first two phases; associated SNPs from Phase III were used for replication in Phase IV; finally in Phase V, a multi-ethnic meta-analysis of all samples from four ethnicities was performed. At an array-wide significance (P<2.40E-06), we identify novel BMI associations in loci TOMM40-APOE-APOC1 (rs2075650, P=2.95E-10), SREBF2 (a sterol regulatory element binding transcription factor gene, rs5996074, P=9.43E-07) and NTRK2 (a BDNF receptor, rs1211166, P=1.04E-06) in the Phase IV meta-analysis. Of ten loci with previous evidence for BMI association represented on IBC array, eight were replicated, with the remaining two showing nominal significance. Conditional analyses revealed two independent BMI associated signals in BDNF and MC4R regions. Of the 11 array-wide significant SNPs, three are associated with gene expression levels in both primary B-cells and monocytes; with rs4788099 in SH2B1 notably being associated with the expression of multiple genes in cis. These multi-ethnic meta-analyses expand our knowledge of BMI genetics

IGVBrowser–a genomic variation resource from diverse Indian populations

The Indian Genome Variation Consortium (IGVC) project, an initiative of the Council for Scientific and Industrial Research, has been the first large-scale comprehensive study of the Indian population. One of the major aims of the project is to study and catalog the variations in nearly thousand candidate genes related to diseases and drug response for predictive marker discovery, founder identification and also to address questions related to ethnic diversity, migrations, extent and relatedness with other world population. The Phase I of the project aimed at providing a set of reference populations that would represent the entire genetic spectrum of India in terms of language, ethnicity and geography and Phase II in providing variation data on candidate genes and genome wide neutral markers on these reference set of populations. We report here development of the IGVBrowser that provides allele and genotype frequency data generated in the IGVC project. The database harbors 4229 SNPs from more than 900 candidate genes in contrasting Indian populations. Analysis shows that most of the markers are from genic regions. Further, a large fraction of genes are implicated in cardiovascular, metabolic, cancer and immune system-related diseases. Thus, the IGVC data provide a basal level variation data in Indian population to study genetic diseases and pharmacology. Additionally, it also houses data on ∼50 000 (Affy 50 K array) genome wide neutral markers in these reference populations. In IGVBrowser one can analyze and compare genomic variations in Indian population with those reported in HapMap along with annotation information from various primary data sources

IGVBrowser–a genomic variation resource from diverse Indian populations

The Indian Genome Variation Consortium (IGVC) project, an initiative of the Council for Scientific and Industrial Research, has been the first large-scale comprehensive study of the Indian population. One of the major aims of the project is to study and catalog the variations in nearly thousand candidate genes related to diseases and drug response for predictive marker discovery, founder identification and also to address questions related to ethnic diversity, migrations, extent and relatedness with other world population. The Phase I of the project aimed at providing a set of reference populations that would represent the entire genetic spectrum of India in terms of language, ethnicity and geography and Phase II in providing variation data on candidate genes and genome wide neutral markers on these reference set of populations. We report here development of the IGVBrowser that provides allele and genotype frequency data generated in the IGVC project. The database harbors 4229 SNPs from more than 900 candidate genes in contrasting Indian populations. Analysis shows that most of the markers are from genic regions. Further, a large fraction of genes are implicated in cardiovascular, metabolic, cancer and immune system-related diseases. Thus, the IGVC data provide a basal level variation data in Indian population to study genetic diseases and pharmacology. Additionally, it also houses data on ∼50 000 (Affy 50 K array) genome wide neutral markers in these reference populations. In IGVBrowser one can analyze and compare genomic variations in Indian population with those reported in HapMap along with annotation information from various primary data sources

A multilocus assay reveals high nucleotide diversity and limited differentiation among Scandinavian willow grouse (Lagopus lagopus)

<p>Abstract</p> <p>Background</p> <p>There is so far very little data on autosomal nucleotide diversity in birds, except for data from the domesticated chicken and some passerines species. Estimates of nucleotide diversity reported so far in birds have been high (~10^-3) and a likely explanation for this is the generally higher effective population sizes compared to mammals. In this study, the level of nucleotide diversity has been examined in the willow grouse, a non-domesticated bird species from the order Galliformes, which also holds the chicken. The willow grouse (<it>Lagopus lagopus</it>) has an almost circumpolar distribution but is absent from Greenland and the north Atlantic islands. It primarily inhabits tundra, forest edge habitats and sub-alpine vegetation. Willow grouse are hunted throughout its range, and regionally it is a game bird of great cultural and economical importance.</p> <p>Results</p> <p>We sequenced 18 autosomal protein coding loci from approximately 15–18 individuals per population. We found a total of 127 SNP's, which corresponds to 1 SNP every 51 bp. 26 SNP's were amino acid replacement substitutions. Total nucleotide diversity (<it>π</it>_<it>t</it>) was between 1.30 × 10^-4and 7.66 × 10^-3(average <it>π</it>_{<it>t </it>}= 2.72 × 10^-3± 2.06 × 10^-3) and silent nucleotide diversity varied between 4.20 × 10^-4and 2.76 × 10^-2(average <it>π</it>_{<it>S </it>}= 9.22 × 10^-3± 7.43 × 10^-4). The synonymous diversity is approximately 20 times higher than in humans and two times higher than in chicken. Non-synonymous diversity was on average 18 times lower than the synonymous diversity and varied between 0 and 4.90 × 10^-3(average <it>π</it>_{<it>a </it>}= 5.08 × 10^-4± 7.43 × 10³), which suggest that purifying selection is strong in these genes. <it>F</it>_STvalues based on synonymous SNP's varied between -5.60 × 10^-4and 0.20 among loci and revealed low levels of differentiation among the four localities, with an overall value of <it>F</it>_ST= 0.03 (95% CI: 0.006 – 0.057) over 60 unlinked loci. Non-synonymous SNP's gave similar results. Low levels of linkage disequilibrium were observed within genes, with an average r²= 0.084 ± 0.110, which is expected for a large outbred population with no population differentiation. The mean per site per generation recombination parameter (ρ) was comparably high (0.028 ± 0.018), indicating high recombination rates in these genes.</p> <p>Conclusion</p> <p>We found unusually high levels of nucleotide diversity in the Scandinavian willow grouse as well as very little population structure among localities with up to 1647 km distance. There are also low levels of linkage disequilibrium within the genes and the population recombination rate is high, which is indicative of an old panmictic population, where recombination has had time to break up any haplotype blocks. The non-synonymous nucleotide diversity is low compared with the silent, which is in agreement with effective purifying selection, possibly due to the large effective population size.</p