The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage

BACKGROUND: The "out of Africa" model postulating single "southern route" dispersal posits arrival of "Anatomically Modern Human" to Indian subcontinent around 66–70 thousand years before present (kyBP). However the contributions and legacy of these earliest settlers in contemporary Indian populations, owing to the complex past population dynamics and later migrations has been an issue of controversy. The high frequency of mitochondrial lineage "M2" consistent with its greater age and distribution suggests that it may represent the phylogenetic signature of earliest settlers. Accordingly, we attempted to re-evaluate the impact and contribution of earliest settlers in shaping the genetic diversity and structure of contemporary Indian populations; using our newly sequenced 72 and 4 published complete mitochondrial genomes of this lineage. RESULTS: The M2 lineage, harbouring two deep rooting subclades M2a and M2b encompasses approximately one tenth of the mtDNA pool of studied tribes. The phylogeographic spread and diversity indices of M2 and its subclades among the tribes of different geographic regions and linguistic phyla were investigated in detail. Further the reconstructed demographic history of M2 lineage as a surrogate of earliest settlers' component revealed that the demographic events with pronounced regional variations had played pivotal role in shaping the complex net of populations phylogenetic relationship in Indian subcontinent. CONCLUSION: Our results suggest that tribes of southern and eastern region along with Dravidian and Austro-Asiatic speakers of central India are the modern representatives of earliest settlers of subcontinent. The Last Glacial Maximum aridity and post LGM population growth mechanised some sort of homogeneity and redistribution of earliest settlers' component in India. The demic diffusion of agriculture and associated technologies around 3 kyBP, which might have marginalized hunter-gatherer, is coincidental with the decline of earliest settlers' population during this period

Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial.

BACKGROUND: Child stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe. METHODS: We did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940. FINDINGS: Between Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08-0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28-2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported. INTERPRETATION: Household-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not reduce diarrhoea. Implementation of these WASH interventions in combination with IYCF interventions is unlikely to reduce stunting or anaemia more than implementation of IYCF alone. FUNDING: Bill & Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Development Cooperation, UNICEF, and US National Institutes of Health.The SHINE trial is funded by the Bill & Melinda Gates Foundation (OPP1021542 and OPP113707); UK Department for International Development; Wellcome Trust, UK (093768/Z/10/Z, 108065/Z/15/Z and 203905/Z/16/Z); Swiss Agency for Development and Cooperation; US National Institutes of Health (2R01HD060338-06); and UNICEF (PCA-2017-0002)

Genetic variants in leptin: determinants of obesity and leptin levels in South Indian population

The revelation of leptin action mechanisms has led to various attempts to establish the association of polymorphisms in the leptin gene with obesity-related phenotypes. But, outcomes have been contradicting, which made the information on the role of the leptin gene in regulating the mechanism of pathophysiology of obesity inexplicable. Moreover, none of the studies are known to have similar implications on the Indian population. To address such contradictions, our study aims to evaluate the association of leptin gene polymorphism with obesity and leptin levels in a South Indian Population. A total of 304 cases (BMI >= 27.5) and 309 controls (BMI <= 23) from local inhabitants of Mysore, Karnataka were recruited for the study. The leptin gene variants rs7799039, rs2167270 and rs4731426 independently, as well as in 4 haplotype combinations, were found to be significantly associated with the risk of obesity. An increasing trend in BMI and leptin levels was observed with every addition of A and C minor alleles of exonic variant (rs2167270) and intronic variant (rs4731426) respectively. However, only AA genotype of SNP rs7799039 was positively associated with BMI. None of the SNPs were associated with fat percentage and waist to hip ratio. On a whole, this data suggests that the common polymorphisms in the leptin gene are strong predictors of obesity and leptin levels in South Indians

Menopause versus aging: The predictor of obesity and metabolic aberrations among menopausal women of Karnataka, South India

Context: Increased incidences of cardiovascular disorder and metabolic syndrome particularly after menopause have raised curiosity for the underlying factors. However, it is still a debate whether age or menopausal transition is a greater contributor.Aims: To elucidate the inter-relationships of age, menopause, and associated obesity and to assess their independent effects on aggravation of cardio metabolic risk factors in postmenopausal women.Settings and Design: Four hundred two women aged between 30 and 75 years were recruited in a cross-sectional study from Southern India. Three hundred sixteen participants exempting exclusion criteria, comprising of 169 premenopaus aland147 postmenopausal women were finally included.Materials and Methods: Anthropometric measurements such as weight, height, waist circumference (WC), hip circumference (HC), fat percentage, basal metabolic rate (BMR), and blood pressure were taken. Fasting plasmaglucose, postprandialglucose, glycated hemoglobin(HbA1c), lipidprofile, and C-reactive protein(CRP) were also measured.Statistical Analysis Used: Independent t-test, Analysis of covariates (ANCOVA), Pearson’s correlation coefficients and multiple stepwise line arregression model analysis were done. Results:A significant increase in physical and metabolic factors was observed in postmenopausal women compared to premenopausal women except WC and HbA1c. Contrastingly, high-density lipoprotein cholesterol (HDL)levels and BMR were significantly decreased. After adjusting for BMI and age,the significant differences in the variables through the menopausal transition persisted, including an increase in WC. Significant correlation was observed between age and measures of general obesity such as BMI (P < 0.05) and fat percentage (P<0.001) but not with central obesity indices. Menopausal status and WC exerted an independent effect on most of the metabolic risk factors (P < 0.001 or P < 0.01). Fat percentage was the predicting variable for CRP, HbA1c, diastolic blood pressure (P < 0.001), and HDL (P < 0.01). But Age showed independent effect only on HbA1c.Conclusions: Menopausal transition brings about anomalies in total body composition characterized by an increased body fat mass and central adiposity. This creates a compatible atmosphere for abnormal metabolism and aggravated cardio metabolic risk factors. Thus, menopausal status and associated obesity is the major predictor of metabolic aberrations over age in menopausal women

MTNR1B gene polymorphisms and susceptibility to type 2 diabetes: a pilot study in South Indians

Type 2 Diabetes (T2D) is the major health concern in the Indian subcontinent. A genome-wide association study carried out with non-diabetic Indians showed association of MTNR1B variants with fasting glucose. MTNR1B mediates the effect of melatonin on insulin secretion. In light of the growing importance of MTNR1B in the etiology of T2D, we sought to test its association with the disease in the south Indian type 2 diabetics. Five single nucleotide polymorphisms of MTNR1B (rs10830962, rs10830963, rs3847554, rs1387153 and rs2166706) were genotyped in 346 T2D patients and 341 non-diabetic controls. None of the SNPs differed significantly between patients and controls with respect to allele and genotype frequencies. Linear regression analysis after adjustment for age, sex and BMI showed a significant positive association of rs3847554 with fasting glucose under recessive model (beta = 14.98, p = 0.012). Haplotypes constituted by minor alleles of rs3847554, rs1387153, rs2166706, rs10830963 and major allele of rs10830962 showed significant positive correlation with fasting glucose (p<0.05). Though the results obtained are suggestive of MTNR1B role in T2D etiology, they need to be confirmed with much larger sample sizes. (C) 2015 Elsevier B.V. All rights reserved

The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage

Abstract Background The "out of Africa" model postulating single "southern route" dispersal posits arrival of "Anatomically Modern Human" to Indian subcontinent around 66–70 thousand years before present (kyBP). However the contributions and legacy of these earliest settlers in contemporary Indian populations, owing to the complex past population dynamics and later migrations has been an issue of controversy. The high frequency of mitochondrial lineage "M2" consistent with its greater age and distribution suggests that it may represent the phylogenetic signature of earliest settlers. Accordingly, we attempted to re-evaluate the impact and contribution of earliest settlers in shaping the genetic diversity and structure of contemporary Indian populations; using our newly sequenced 72 and 4 published complete mitochondrial genomes of this lineage. Results The M2 lineage, harbouring two deep rooting subclades M2a and M2b encompasses approximately one tenth of the mtDNA pool of studied tribes. The phylogeographic spread and diversity indices of M2 and its subclades among the tribes of different geographic regions and linguistic phyla were investigated in detail. Further the reconstructed demographic history of M2 lineage as a surrogate of earliest settlers' component revealed that the demographic events with pronounced regional variations had played pivotal role in shaping the complex net of populations phylogenetic relationship in Indian subcontinent. Conclusion Our results suggest that tribes of southern and eastern region along with Dravidian and Austro-Asiatic speakers of central India are the modern representatives of earliest settlers of subcontinent. The Last Glacial Maximum aridity and post LGM population growth mechanised some sort of homogeneity and redistribution of earliest settlers' component in India. The demic diffusion of agriculture and associated technologies around 3 kyBP, which might have marginalized hunter-gatherer, is coincidental with the decline of earliest settlers' population during this period.</p

The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage-2

Ur additional complete mtDNA sequence of M2 lineage (labeled as R102, T3, T11 and T27) are acquired from published sources [] has been used for tree reconstruction. Suffixes A, C, G, and T indicate transversions, "d" signifies a deletion and a plus sign (+) an insertion; recurrent mutations are underlined. The prefix "@" indicates back mutation. The coalescent estimates were calculated as per [] and [] presented as bold and Italic respectively.<p><b>Copyright information:</b></p><p>Taken from "The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage"</p><p>http://www.biomedcentral.com/1471-2148/8/230</p><p>BMC Evolutionary Biology 2008;8():230-230.</p><p>Published online 11 Aug 2008</p><p>PMCID:PMC2528015.</p><p></p

The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage-1

PD) limits. Panel 'A'- The Bayesian skyline plot (= 10) for India total, derived from complete mtDNA sequences (= 76). Panel 'B'- The Bayesian skyline plot (= 10) for India total, derived from coding region (577–16023) mtDNA sequences (= 76). The time estimates (yBP) were calculated as per []. For comparison, the cold and arid period around the Last Glacial Maximum are also indicated on panel A & B. Panel 'C to F' shows Bayesian skyline plots (= 10) derived from complete mtDNA sequences of eastern (n = 11), central (n = 29), southern (n = 14) and western (n = 22) regions of India respectively.<p><b>Copyright information:</b></p><p>Taken from "The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage"</p><p>http://www.biomedcentral.com/1471-2148/8/230</p><p>BMC Evolutionary Biology 2008;8():230-230.</p><p>Published online 11 Aug 2008</p><p>PMCID:PMC2528015.</p><p></p

The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage-0

Ur additional complete mtDNA sequence of M2 lineage (labeled as R102, T3, T11 and T27) are acquired from published sources [] has been used for tree reconstruction. Suffixes A, C, G, and T indicate transversions, "d" signifies a deletion and a plus sign (+) an insertion; recurrent mutations are underlined. The prefix "@" indicates back mutation. The coalescent estimates were calculated as per [] and [] presented as bold and Italic respectively.<p><b>Copyright information:</b></p><p>Taken from "The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage"</p><p>http://www.biomedcentral.com/1471-2148/8/230</p><p>BMC Evolutionary Biology 2008;8():230-230.</p><p>Published online 11 Aug 2008</p><p>PMCID:PMC2528015.</p><p></p