Author Correction: The genetic legacy of continental scale admixture in Indian Austroasiatic speakers.

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The genetic legacy of continental scale admixture in Indian Austroasiatic speakers.

Surrounded by speakers of Indo-European, Dravidian and Tibeto-Burman languages, around 11 million Munda (a branch of Austroasiatic language family) speakers live in the densely populated and genetically diverse South Asia. Their genetic makeup holds components characteristic of South Asians as well as Southeast Asians. The admixture time between these components has been previously estimated on the basis of archaeology, linguistics and uniparental markers. Using genome-wide genotype data of 102 Munda speakers and contextual data from South and Southeast Asia, we retrieved admixture dates between 2000-3800 years ago for different populations of Munda. The best modern proxies for the source populations for the admixture with proportions 0.29/0.71 are Lao people from Laos and Dravidian speakers from Kerala in India. The South Asian population(s), with whom the incoming Southeast Asians intermixed, had a smaller proportion of West Eurasian genetic component than contemporary proxies. Somewhat surprisingly Malaysian Peninsular tribes rather than the geographically closer Austroasiatic languages speakers like Vietnamese and Cambodians show highest sharing of IBD segments with the Munda. In addition, we affirmed that the grouping of the Munda speakers into North and South Munda based on linguistics is in concordance with genome-wide data.

Genetic Interaction Between Two VNTRs in the SLC6A4 Gene Regulates Nicotine Dependence in Vietnamese Men.

Nicotine dependence is an addiction to tobacco products and a global public health concern. Association between the SLC6A4 polymorphisms and nicotine dependence is controversial. Two variable number tandem repeat (VNTR) domains, termed HTTLPR and STin2, in the SLC6A4 gene are well characterized transcriptional regulatory elements. Their polymorphism in the copy number of the repeat correlates with the particular personality and psychiatric traits. We analyzed nicotine dependence in 1,804 participants from Central Vietnam. The Fagerström Test (FTND) was used to evaluate the nicotine dependence and PCR was used to determine the SLC6A4 HTTLPR and STin2 VNTRs. The HTTLPR VNTR was associated with difficulties to refrain from smoking in a prohibiting environment. The STIn2 10/10 genotype was associated with (1) years of smoking, (2) difficulties to quit the first cigarette, and (3) higher number of cigarettes smoked per day (CPD). Stratification analysis was used to find the genetic interaction between these two VNTRs in nicotine dependence as they may synergistically regulate the SLC6A4 expression. Smokers with the S/S HTTLPR genotypes showed a much stronger association between STin2 10/10 variant and CPD. This finding is consistent with the molecular evidence for the functional interaction between HTTLPR and STin2 in cell line models, where STin2 has described as a stronger expressional regulator. Similarly, we found that STin2 is a much stronger modifier of smoking with 10/10 genotype related to higher nicotine dependence. The present study supports genetic interaction between HTTLPR and STin2 VNTRs in the regulation of nicotine dependence with the dominance of the STin2 effects. This finding could be explained by their differential effect on the SLC6A4 expression.

Mutation analysis of the COL1A1 and COL1A2 genes in Vietnamese patients with osteogenesis imperfecta.

BACKGROUND: The genetics of osteogenesis imperfecta (OI) have not been studied in a Vietnamese population before. We performed mutational analysis of the COL1A1 and COL1A2 genes in 91 unrelated OI patients of Vietnamese origin. We then systematically characterized the mutation profiles of these two genes which are most commonly related to OI. METHODS: Genomic DNA was extracted from EDTA-preserved blood according to standard high-salt extraction methods. Sequence analysis and pathogenic variant identification was performed with Mutation Surveyor DNA variant analysis software. Prediction of the pathogenicity of mutations was conducted using Alamut Visual software. The presence of variants was checked against Dalgleish's osteogenesis imperfecta mutation database. RESULTS: The sample consisted of 91 unrelated osteogenesis imperfecta patients. We identified 54 patients with COL1A1/2 pathogenic variants; 33 with COL1A1 and 21 with COL1A2. Two patients had multiple pathogenic variants. Seventeen novel COL1A1 and 10 novel COL1A2 variants were identified. The majority of identified COL1A1/2 pathogenic variants occurred in a glycine substitution (36/56, 64.3 %), usually serine (23/36, 63.9 %). We found two pathogenic variants of the COL1A1 gene c.2461G > A (p.Gly821Ser) in four unrelated patients and one, c.2005G > A (p.Ala669Thr), in two unrelated patients. CONCLUSION: Our data showed a lower number of collagen OI pathogenic variants in Vietnamese patients compared to reported rates for Asian populations. The OI mutational profile of the Vietnamese population is unique and related to the presence of a high number of recessive mutations in non-collagenous OI genes. Further analysis of OI patients negative for collagen mutations, is required.