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1.  Y-chromosome evidence suggests a common paternal heritage of Austro-Asiatic populations 
Background
The Austro-Asiatic linguistic family, which is considered to be the oldest of all the families in India, has a substantial presence in Southeast Asia. However, the possibility of any genetic link among the linguistic sub-families of the Indian Austro-Asiatics on the one hand and between the Indian and the Southeast Asian Austro-Asiatics on the other has not been explored till now. Therefore, to trace the origin and historic expansion of Austro-Asiatic groups of India, we analysed Y-chromosome SNP and STR data of the 1222 individuals from 25 Indian populations, covering all the three branches of Austro-Asiatic tribes, viz. Mundari, Khasi-Khmuic and Mon-Khmer, along with the previously published data on 214 relevant populations from Asia and Oceania.
Results
Our results suggest a strong paternal genetic link, not only among the subgroups of Indian Austro-Asiatic populations but also with those of Southeast Asia. However, maternal link based on mtDNA is not evident. The results also indicate that the haplogroup O-M95 had originated in the Indian Austro-Asiatic populations ~65,000 yrs BP (95% C.I. 25,442 – 132,230) and their ancestors carried it further to Southeast Asia via the Northeast Indian corridor. Subsequently, in the process of expansion, the Mon-Khmer populations from Southeast Asia seem to have migrated and colonized Andaman and Nicobar Islands at a much later point of time.
Conclusion
Our findings are consistent with the linguistic evidence, which suggests that the linguistic ancestors of the Austro-Asiatic populations have originated in India and then migrated to Southeast Asia.
doi:10.1186/1471-2148-7-47
PMCID: PMC1851701  PMID: 17389048
2.  Phylogeography of mtDNA haplogroup R7 in the Indian peninsula 
Background
Human genetic diversity observed in Indian subcontinent is second only to that of Africa. This implies an early settlement and demographic growth soon after the first 'Out-of-Africa' dispersal of anatomically modern humans in Late Pleistocene. In contrast to this perspective, linguistic diversity in India has been thought to derive from more recent population movements and episodes of contact. With the exception of Dravidian, which origin and relatedness to other language phyla is obscure, all the language families in India can be linked to language families spoken in different regions of Eurasia. Mitochondrial DNA and Y chromosome evidence has supported largely local evolution of the genetic lineages of the majority of Dravidian and Indo-European speaking populations, but there is no consensus yet on the question of whether the Munda (Austro-Asiatic) speaking populations originated in India or derive from a relatively recent migration from further East.
Results
Here, we report the analysis of 35 novel complete mtDNA sequences from India which refine the structure of Indian-specific varieties of haplogroup R. Detailed analysis of haplogroup R7, coupled with a survey of ~12,000 mtDNAs from caste and tribal groups over the entire Indian subcontinent, reveals that one of its more recently derived branches (R7a1), is particularly frequent among Munda-speaking tribal groups. This branch is nested within diverse R7 lineages found among Dravidian and Indo-European speakers of India. We have inferred from this that a subset of Munda-speaking groups have acquired R7 relatively recently. Furthermore, we find that the distribution of R7a1 within the Munda-speakers is largely restricted to one of the sub-branches (Kherwari) of northern Munda languages. This evidence does not support the hypothesis that the Austro-Asiatic speakers are the primary source of the R7 variation. Statistical analyses suggest a significant correlation between genetic variation and geography, rather than between genes and languages.
Conclusion
Our high-resolution phylogeographic study, involving diverse linguistic groups in India, suggests that the high frequency of mtDNA haplogroup R7 among Munda speaking populations of India can be explained best by gene flow from linguistically different populations of Indian subcontinent. The conclusion is based on the observation that among Indo-Europeans, and particularly in Dravidians, the haplogroup is, despite its lower frequency, phylogenetically more divergent, while among the Munda speakers only one sub-clade of R7, i.e. R7a1, can be observed. It is noteworthy that though R7 is autochthonous to India, and arises from the root of hg R, its distribution and phylogeography in India is not uniform. This suggests the more ancient establishment of an autochthonous matrilineal genetic structure, and that isolation in the Pleistocene, lineage loss through drift, and endogamy of prehistoric and historic groups have greatly inhibited genetic homogenization and geographical uniformity.
doi:10.1186/1471-2148-8-227
PMCID: PMC2529308  PMID: 18680585
3.  Genetic Structure of Tibeto-Burman Populations of Bangladesh: Evaluating the Gene Flow along the Sides of Bay-of-Bengal 
PLoS ONE  2013;8(10):e75064.
Human settlement and migrations along sides of Bay-of-Bengal have played a vital role in shaping the genetic landscape of Bangladesh, Eastern India and Southeast Asia. Bangladesh and Northeast India form the vital land bridge between the South and Southeast Asia. To reconstruct the population history of this region and to see whether this diverse region geographically acted as a corridor or barrier for human interaction between South Asia and Southeast Asia, we, for the first time analyzed high resolution uniparental (mtDNA and Y chromosome) and biparental autosomal genetic markers among aboriginal Bangladesh tribes currently speaking Tibeto-Burman language. All the three studied populations; Chakma, Marma and Tripura from Bangladesh showed strikingly high homogeneity among themselves and strong affinities to Northeast Indian Tibeto-Burman groups. However, they show substantially higher molecular diversity than Northeast Indian populations. Unlike Austroasiatic (Munda) speakers of India, we observed equal role of both males and females in shaping the Tibeto-Burman expansion in Southern Asia. Moreover, it is noteworthy that in admixture proportion, TB populations of Bangladesh carry substantially higher mainland Indian ancestry component than Northeast Indian Tibeto-Burmans. Largely similar expansion ages of two major paternal haplogroups (O2a and O3a3c), suggested that they arose before the differentiation of any language group and approximately at the same time. Contrary to the scenario proposed for colonization of Northeast India as male founder effect that occurred within the past 4,000 years, we suggest a significantly deep colonization of this region. Overall, our extensive analysis revealed that the population history of South Asian Tibeto-Burman speakers is more complex than it was suggested before.
doi:10.1371/journal.pone.0075064
PMCID: PMC3794028  PMID: 24130682
4.  Reconstructing Austronesian population history in Island Southeast Asia 
Nature Communications  2014;5:4689.
Austronesian languages are spread across half the globe, from Easter Island to Madagascar. Evidence from linguistics and archaeology indicates that the ‘Austronesian expansion,’ which began 4,000–5,000 years ago, likely had roots in Taiwan, but the ancestry of present-day Austronesian-speaking populations remains controversial. Here, we analyse genome-wide data from 56 populations using new methods for tracing ancestral gene flow, focusing primarily on Island Southeast Asia. We show that all sampled Austronesian groups harbour ancestry that is more closely related to aboriginal Taiwanese than to any present-day mainland population. Surprisingly, western Island Southeast Asian populations have also inherited ancestry from a source nested within the variation of present-day populations speaking Austro-Asiatic languages, which have historically been nearly exclusive to the mainland. Thus, either there was once a substantial Austro-Asiatic presence in Island Southeast Asia, or Austronesian speakers migrated to and through the mainland, admixing there before continuing to western Indonesia.
Populations speaking Austronesian languages are numerous and widespread, but their history remains controversial. Here, the authors analyse genetic data from Southeast Asia and show that all populations harbour ancestry most closely related to aboriginal Taiwanese, while some also contain a component closest to Austro-Asiatic speakers.
doi:10.1038/ncomms5689
PMCID: PMC4143916  PMID: 25137359
5.  Evolutionary History of Helicobacter pylori Sequences Reflect Past Human Migrations in Southeast Asia 
PLoS ONE  2011;6(7):e22058.
The human population history in Southeast Asia was shaped by numerous migrations and population expansions. Their reconstruction based on archaeological, linguistic or human genetic data is often hampered by the limited number of informative polymorphisms in classical human genetic markers, such as the hypervariable regions of the mitochondrial DNA. Here, we analyse housekeeping gene sequences of the human stomach bacterium Helicobacter pylori from various countries in Southeast Asia and we provide evidence that H. pylori accompanied at least three ancient human migrations into this area: i) a migration from India introducing hpEurope bacteria into Thailand, Cambodia and Malaysia; ii) a migration of the ancestors of Austro-Asiatic speaking people into Vietnam and Cambodia carrying hspEAsia bacteria; and iii) a migration of the ancestors of the Thai people from Southern China into Thailand carrying H. pylori of population hpAsia2. Moreover, the H. pylori sequences reflect iv) the migrations of Chinese to Thailand and Malaysia within the last 200 years spreading hspEasia strains, and v) migrations of Indians to Malaysia within the last 200 years distributing both hpAsia2 and hpEurope bacteria. The distribution of the bacterial populations seems to strongly influence the incidence of gastric cancer as countries with predominantly hspEAsia isolates exhibit a high incidence of gastric cancer while the incidence is low in countries with a high proportion of hpAsia2 or hpEurope strains. In the future, the host range expansion of hpEurope strains among Asian populations, combined with human motility, may have a significant impact on gastric cancer incidence in Asia.
doi:10.1371/journal.pone.0022058
PMCID: PMC3139604  PMID: 21818291
6.  Unravelling the Genetic History of Negritos and Indigenous Populations of Southeast Asia 
Genome Biology and Evolution  2015;7(5):1206-1215.
Indigenous populations of Malaysia known as Orang Asli (OA) show huge morphological, anthropological, and linguistic diversity. However, the genetic history of these populations remained obscure. We performed a high-density array genotyping using over 2 million single nucleotide polymorphisms in three major groups of Negrito, Senoi, and Proto-Malay. Structural analyses indicated that although all OA groups are genetically closest to East Asian (EA) populations, they are substantially distinct. We identified a genetic affinity between Andamanese and Malaysian Negritos which may suggest an ancient link between these two groups. We also showed that Senoi and Proto-Malay may be admixtures between Negrito and EA populations. Formal admixture tests provided evidence of gene flow between Austro-Asiatic-speaking OAs and populations from Southeast Asia (SEA) and South China which suggest a widespread presence of these people in SEA before Austronesian expansion. Elevated linkage disequilibrium (LD) and enriched homozygosity found in OAs reflect isolation and bottlenecks experienced. Estimates based on Ne and LD indicated that these populations diverged from East Asians during the late Pleistocene (14.5 to 8 KYA). The continuum in divergence time from Negritos to Senoi and Proto-Malay in combination with ancestral markers provides evidences of multiple waves of migration into SEA starting with the first Out-of-Africa dispersals followed by Early Train and subsequent Austronesian expansions.
doi:10.1093/gbe/evv065
PMCID: PMC4453060  PMID: 25877615
Negritos; Senoi; Proto-Malay; population genetics; SNPs
7.  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.
doi:10.1186/1471-2148-8-230
PMCID: PMC2528015  PMID: 18691441
8.  Deep Rooting In-Situ Expansion of mtDNA Haplogroup R8 in South Asia 
PLoS ONE  2009;4(8):e6545.
Background
The phylogeny of the indigenous Indian-specific mitochondrial DNA (mtDNA) haplogroups have been determined and refined in previous reports. Similar to mtDNA superhaplogroups M and N, a profusion of reports are also available for superhaplogroup R. However, there is a dearth of information on South Asian subhaplogroups in particular, including R8. Therefore, we ought to access the genealogy and pre-historic expansion of haplogroup R8 which is considered one of the autochthonous lineages of South Asia.
Methodology/Principal Findings
Upon screening the mtDNA of 5,836 individuals belonging to 104 distinct ethnic populations of the Indian subcontinent, we found 54 individuals with the HVS-I motif that defines the R8 haplogroup. Complete mtDNA sequencing of these 54 individuals revealed two deep-rooted subclades: R8a and R8b. Furthermore, these subclades split into several fine subclades. An isofrequency contour map detected the highest frequency of R8 in the state of Orissa. Spearman's rank correlation analysis suggests significant correlation of R8 occurrence with geography.
Conclusions/Significance
The coalescent age of newly-characterized subclades of R8, R8a (15.4±7.2 Kya) and R8b (25.7±10.2 Kya) indicates that the initial maternal colonization of this haplogroup occurred during the middle and upper Paleolithic period, roughly around 40 to 45 Kya. These results signify that the southern part of Orissa currently inhabited by Munda speakers is likely the origin of these autochthonous maternal deep-rooted haplogroups. Our high-resolution study on the genesis of R8 haplogroup provides ample evidence of its deep-rooted ancestry among the Orissa (Austro-Asiatic) tribes.
doi:10.1371/journal.pone.0006545
PMCID: PMC2718812  PMID: 19662095
9.  An Updated Phylogeny of the Human Y-Chromosome Lineage O2a-M95 with Novel SNPs 
PLoS ONE  2014;9(6):e101020.
Though the Y-chromosome O2a-M95 lineage is one of the major haplogroups present in eastern Asian populations, especially among Austro-Asiatic speaking populations from Southwestern China and mainland Southeast Asia, to date its phylogeny lacks structure due to only one downstream SNP marker (M88) assigned to the lineage. A recent array-capture-based Y chromosome sequencing of Asian samples has yielded a variety of novel SNPs purportedly belonging to the O2a-M95 lineage, but their phylogenetic positions have yet to be determined. In this study, we sampled 646 unrelated males from 22 Austro-Asiatic speaking populations from Cambodia, Thailand and Southwestern China, and genotyped 12 SNP makers among the sampled populations, including 10 of the newly reported markers. Among the 646 males, 343 belonged to the O2a-M95 lineage, confirming the supposed dominance of this Y chromosome lineage in Austro-Asiatic speaking populations. We further characterized the phylogeny of O2a-M95 by defining 5 sub-branches: O2a1*-M95, O2a1a-F789, O2a1b*-F1252, O2a1b1*-M88 and O2a1b1a -F761. This updated phylogeny not only improves the resolution of this lineage, but also allows for greater tracing of the prehistory of human populations in eastern Asia and the Pacific, which may yield novel insights into the patterns of language diversification and population movement in these regions.
doi:10.1371/journal.pone.0101020
PMCID: PMC4074153  PMID: 24972021
10.  Nasopharyngeal carcinoma as a paradigm of cancer genetics 
Chinese Journal of Cancer  2011;30(2):79-84.
The unusual incidence patterns for nasopharyngeal carcinoma (NPC) in China, Northeast India, Arctic Inuit, Peninsular and island Southeast Asia, Polynesian Islanders, and North Africans indicate a role for NPC risk genes in Chinese, Chinese-related, and not-obviously Chinese-related populations. Renewed interest in NPC genetic risk has been stimulated by a hypothesis that NPC population patterns originated in Bai-Yue / pre-Austronesian–speaking aborigines and were dispersed during the last glacial maximum by Sundaland submersion. Five articles in this issue of the Chinese Journal of Cancer, first presented at a meeting on genetic aspects of NPC [National Cancer Center of Singapore (NCCS), February 20–21, 2010], are directed towards incidence patterns, to early detection of affected individuals within risk populations, and to the application of genetic technology advances to understanding the nature of high risk. Turnbull presents a general framework for understanding population migrations that underlie NPC and similar complex diseases, including other viral cancers. Trejaut et al. apply genetic markers to detail migration from East Asia through Taiwan to the populating of Island Polynesia. Migration dispersal in a westward direction took mongoloid peoples to modern day Northeast India adjacent to Western China (Xinjiang). NPC incidence in mongoloid Nagas ranks amongst the highest in the world, whereas elsewhere in India NPC is uncommon. Cao et al. detail incidence patterns in Southeast China that have occurred over recent decades. Finally, Ji et al. describe the utility of Epstein-Barr virus serostatus in early NPC detection. While genetic risk factors still remain largely unknown, human leukocyte antigen (HLA) genes have been a focus of attention since the discovery of an HLA association with NPC in 1973 and, two years later, that NPC susceptibility in highest-risk Cantonese involved the co-occurrence of multi-HLA locus combinations of HLA genes as chromosome combinations, or haplotypes (e.g. HLA-A2–B46), whereas in relatively lower-risk non-Cantonese Chinese (Hokkiens, Teochews) they appeared to act independently, a strength of association reflecting the 30–50-fold difference in incidence between highest risk Cantonese and lowest-risk Indians. The prototypic haplotype HLA-A2–B46 extends over megabases. An upstream DNA segment (near HLA-DPA1), has close similarity to Gorilla, with no obvious homology to Chimpanzee in current databases, suggesting that a reticulate model of primate evolution may be more appropriate than simple phylogeny. The DNA variation level in this segment is high enough for it to be a hominin remnant. HLA-B46 arose in mongoloids and remains largely limited to Chinese so the question arises as to whether the hominin candidate segment indicates an eastward trek of Homo neanderthalensis or the survival of much earlier Homo erectus? In 2011 sequencing technologies have finally caught up with the requirement to separate parental haplotypes. Recently achieved chromosome separation for whole genome di-haploid genetic and epigenetic analysis of parental inheritance in single individuals will reveal interacting patterns of multi-locus haplotypes as humans move in and through successive environments, thus providing definitive information on the genetic affinities between extant populations, and of the migrations that have led to the global distribution of modern Homo. The challenge can now be met of seeking HLA-associated locations both within and outside the HLA complex on each of the pair of chromosomes. More broadly, for every disease, genetic risk detection will require resolution of the diploid genome as a di-haplome. In the context of NPC, HLA genetic risk complete autosomal di-haplomic sequencing will enable testing of the Wee unitary origin hypothesis of NPC risk even among populations with no apparent mongoloid affinity.
doi:10.5732/cjc.010.10609
PMCID: PMC4013336  PMID: 21272439
11.  Genetic affinities between endogamous and inbreeding populations of Uttar Pradesh 
BMC Genetics  2007;8:12.
Background
India has experienced several waves of migration since the Middle Paleolithic. It is believed that the initial demic movement into India was from Africa along the southern coastal route, approximately 60,000–85,000 years before present (ybp). It has also been reported that there were two other major colonization which included eastward diffusion of Neolithic farmers (Elamo Dravidians) from Middle East sometime between 10,000 and 7,000 ybp and a southern dispersal of Indo Europeans from Central Asia 3,000 ybp. Mongol entry during the thirteenth century A.D. as well as some possible minor incursions from South China 50,000 to 60,000 ybp may have also contributed to cultural, linguistic and genetic diversity in India. Therefore, the genetic affinity and relationship of Indians with other world populations and also within India are often contested. In the present study, we have attempted to offer a fresh and immaculate interpretation on the genetic relationships of different North Indian populations with other Indian and world populations.
Results
We have first genotyped 20 tetra-nucleotide STR markers among 1800 north Indian samples of nine endogamous populations belonging to three different socio-cultural strata. Genetic distances (Nei's DA and Reynold's Fst) were calculated among the nine studied populations, Caucasians and East Asians. This analysis was based upon the allelic profile of 20 STR markers to assess the genetic similarity and differences of the north Indian populations. North Indians showed a stronger genetic relationship with the Europeans (DA 0.0341 and Fst 0.0119) as compared to the Asians (DA 0.1694 and Fst – 0.0718). The upper caste Brahmins and Muslims were closest to Caucasians while middle caste populations were closer to Asians. Finally, three phylogenetic assessments based on two different NJ and ML phylogenetic methods and PC plot analysis were carried out using the same panel of 20 STR markers and 20 geo-ethnic populations. The three phylogenetic assessments revealed that north Indians are clustering with Caucasians.
Conclusion
The genetic affinities of Indians and that of different caste groups towards Caucasians or East Asians is distributed in a cline where geographically north Indians and both upper caste and Muslim populations are genetically closer to the Caucasians.
doi:10.1186/1471-2156-8-12
PMCID: PMC1855350  PMID: 17417972
12.  The Effect of Rural-to-Urban Migration on Obesity and Diabetes in India: A Cross-Sectional Study 
PLoS Medicine  2010;7(4):e1000268.
Shah Ebrahim and colleagues examine the distribution of obesity, diabetes, and other cardiovascular risk factors among urban migrant factory workers in India, together with their rural siblings. The investigators identify patterns of change of cardiovascular risk factors associated with urban migration.
Background
Migration from rural areas of India contributes to urbanisation and may increase the risk of obesity and diabetes. We tested the hypotheses that rural-to-urban migrants have a higher prevalence of obesity and diabetes than rural nonmigrants, that migrants would have an intermediate prevalence of obesity and diabetes compared with life-long urban and rural dwellers, and that longer time since migration would be associated with a higher prevalence of obesity and of diabetes.
Methods and Findings
The place of origin of people working in factories in north, central, and south India was identified. Migrants of rural origin, their rural dwelling sibs, and those of urban origin together with their urban dwelling sibs were assessed by interview, examination, and fasting blood samples. Obesity, diabetes, and other cardiovascular risk factors were compared. A total of 6,510 participants (42% women) were recruited. Among urban, migrant, and rural men the age- and factory-adjusted percentages classified as obese (body mass index [BMI] >25 kg/m2) were 41.9% (95% confidence interval [CI] 39.1–44.7), 37.8% (95% CI 35.0–40.6), and 19.0% (95% CI 17.0–21.0), respectively, and as diabetic were 13.5% (95% CI 11.6–15.4), 14.3% (95% CI 12.2–16.4), and 6.2% (95% CI 5.0–7.4), respectively. Findings for women showed similar patterns. Rural men had lower blood pressure, lipids, and fasting blood glucose than urban and migrant men, whereas no differences were seen in women. Among migrant men, but not women, there was weak evidence for a lower prevalence of both diabetes and obesity among more recent (≤10 y) migrants.
Conclusions
Migration into urban areas is associated with increases in obesity, which drive other risk factor changes. Migrants have adopted modes of life that put them at similar risk to the urban population. Gender differences in some risk factors by place of origin are unexpected and require further exploration.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
India, like the rest of the world, is experiencing an epidemic of diabetes, a chronic disease characterized by dangerous levels of sugar in the blood that cause cardiovascular and kidney disease, which lower life expectancy. The prevalence of diabetes (the proportion of the population with diabetes) has been increasing steadily in India over recent decades, particularly in urban areas. In 1984, only 5% of adults living in the towns and cities of India had diabetes, but by 2004, 15% of adults in urban areas were affected by diabetes. In rural areas of India, diabetes is less common than in urban areas but even here, the prevalence of diabetes is now 6%. Obesity—too much body fat—is a major risk factor for diabetes and, in parallel with the greater increase in diabetes in urban India compared to rural India, there has been a greater increase in obesity in urban areas than in rural areas.
Why Was This Study Done?
Experts think that the increasing prevalence of obesity and diabetes in India (and in other developing countries) is caused in part by increased consumption of saturated fats and sugars and by reduced physical activity, and that these changes are related to urbanization—urban expansion into the countryside and migration from rural to urban areas. If living in an urban setting is a major determinant of obesity and diabetes risk, then people migrating into urban areas should acquire the high risk of the urban population for these two conditions. In this cross-sectional study (a study in which participants are studied at a single time point), the researchers investigate whether rural to urban migrants in India have a higher prevalence of obesity and diabetes than rural nonmigrants. They also ask whether migrants have a prevalence of obesity and diabetes intermediate between that of life-long urban and rural dwellers and whether a longer time since migration is associated with a higher prevalence of obesity and diabetes.
What Did the Researchers Do and Find?
The researchers recruited rural-urban migrants working in four Indian factories in north, central, and south regions and their spouses (if they were living in the same town) into their study. Each migrant worker and spouse asked one nonmigrant brother or sister (sibling) still living in their place of origin to join the study. The researchers also enrolled nonmigrant factory workers and their urban siblings into the study. All the participants (more than 6,500 in total) answered questions about their diet and physical activity and had their fasting blood sugar and their body mass index (BMI; weight in kg divided by height in meters squared) measured; participants with a fasting blood sugar of more than 7.0 nmol/l or a BMI of more than 25 kg/m2 were classified as diabetic or obese, respectively. 41.9% and 37.8% of the urban and migrant men, respectively, but only 19.0% of the rural men were obese. Similarly, 13.5% and 14.3% of the urban and migrant men, respectively, but only 6.2% of the rural men had diabetes. Patterns of obesity and diabetes among the women participants were similar. Finally, although the prevalence of diabetes and obesity was lower in the most recent male migrants than in those who had moved more than 10 years previously, this difference was small and not seen in women migrants.
What Do These Findings Mean?
These findings show that rural-urban migration in India is associated with rapid increases in obesity and in diabetes. They also show that the migrants have adopted modes of life (for example, reduced physical activity) that put them at a similar risk for obesity and diabetes as the urban population. The findings do not show, however, that migrants have an intermediate prevalence of obesity and diabetes compared to urban and rural dwellers and provide only weak support for the idea that a longer time since migration is associated with a higher risk of obesity and diabetes. Although the study's cross-sectional design means that the researchers could not investigate how risk factors for diabetes evolve over time, these findings suggest that urbanization is helping to drive the diabetes epidemic in India. Thus, targeting migrants and their families for health promotion activities and for treatment of risk factors for obesity and diabetes might help to slow the progress of the epidemic.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000268.
The International Diabetes Federation provides information about all aspects of diabetes, including information on diabetes in Southeast Asia (in English, French, and Spanish)
DiabetesIndia.com provides information on the Indian Task Forces on diabetes care in India
Diabetes Foundation (India) has an international collaborative research focus and provides information about health promotion for diabetes; it has also produced consensus guidelines on dietary change for prevention of diabetes in India
The US National Diabetes Information Clearinghouse provides detailed information about diabetes for patients, health care professionals, and the general public (in English and Spanish)
MedlinePlus provides links to further resources and advice about diabetes (in English and Spanish)
doi:10.1371/journal.pmed.1000268
PMCID: PMC2860494  PMID: 20436961
13.  When Indian crabs were not yet Asian - biogeographic evidence for Eocene proximity of India and Southeast Asia 
Background
The faunal and floral relationship of northward-drifting India with its neighboring continents is of general biogeographic interest as an important driver of regional biodiversity. However, direct biogeographic connectivity of India and Southeast Asia during the Cenozoic remains largely unexplored. We investigate timing, direction and mechanisms of faunal exchange between India and Southeast Asia, based on a molecular phylogeny, molecular clock-derived time estimates and biogeographic reconstructions of the Asian freshwater crab family Gecarcinucidae.
Results
Although the Gecarcinucidae are not an element of an ancient Gondwana fauna, their subfamily Gecarcinucinae, and probably also the Liotelphusinae, evolved on the Indian Subcontinent and subsequently dispersed to Southeast Asia. Estimated by a model testing approach, this dispersal event took place during the Middle Eocene, and thus before the final collision of India and the Tibet-part of Eurasia.
Conclusions
We postulate that the India and Southeast Asia were close enough for exchange of freshwater organisms during the Middle Eocene, before the final Indian-Eurasian collision. Our data support geological models that assume the Indian plate having tracked along Southeast Asia during its move northwards.
doi:10.1186/1471-2148-10-287
PMCID: PMC2949875  PMID: 20849594
14.  The Phylogeography of Y-Chromosome Haplogroup H1a1a-M82 Reveals the Likely Indian Origin of the European Romani Populations 
PLoS ONE  2012;7(11):e48477.
Linguistic and genetic studies on Roma populations inhabited in Europe have unequivocally traced these populations to the Indian subcontinent. However, the exact parental population group and time of the out-of-India dispersal have remained disputed. In the absence of archaeological records and with only scanty historical documentation of the Roma, comparative linguistic studies were the first to identify their Indian origin. Recently, molecular studies on the basis of disease-causing mutations and haploid DNA markers (i.e. mtDNA and Y-chromosome) supported the linguistic view. The presence of Indian-specific Y-chromosome haplogroup H1a1a-M82 and mtDNA haplogroups M5a1, M18 and M35b among Roma has corroborated that their South Asian origins and later admixture with Near Eastern and European populations. However, previous studies have left unanswered questions about the exact parental population groups in South Asia. Here we present a detailed phylogeographical study of Y-chromosomal haplogroup H1a1a-M82 in a data set of more than 10,000 global samples to discern a more precise ancestral source of European Romani populations. The phylogeographical patterns and diversity estimates indicate an early origin of this haplogroup in the Indian subcontinent and its further expansion to other regions. Tellingly, the short tandem repeat (STR) based network of H1a1a-M82 lineages displayed the closest connection of Romani haplotypes with the traditional scheduled caste and scheduled tribe population groups of northwestern India.
doi:10.1371/journal.pone.0048477
PMCID: PMC3509117  PMID: 23209554
15.  Autosomal and uniparental portraits of the native populations of Sakha (Yakutia): implications for the peopling of Northeast Eurasia 
Background
Sakha – an area connecting South and Northeast Siberia – is significant for understanding the history of peopling of Northeast Eurasia and the Americas. Previous studies have shown a genetic contiguity between Siberia and East Asia and the key role of South Siberia in the colonization of Siberia.
Results
We report the results of a high-resolution phylogenetic analysis of 701 mtDNAs and 318 Y chromosomes from five native populations of Sakha (Yakuts, Evenks, Evens, Yukaghirs and Dolgans) and of the analysis of more than 500,000 autosomal SNPs of 758 individuals from 55 populations, including 40 previously unpublished samples from Siberia. Phylogenetically terminal clades of East Asian mtDNA haplogroups C and D and Y-chromosome haplogroups N1c, N1b and C3, constituting the core of the gene pool of the native populations from Sakha, connect Sakha and South Siberia. Analysis of autosomal SNP data confirms the genetic continuity between Sakha and South Siberia. Maternal lineages D5a2a2, C4a1c, C4a2, C5b1b and the Yakut-specific STR sub-clade of Y-chromosome haplogroup N1c can be linked to a migration of Yakut ancestors, while the paternal lineage C3c was most likely carried to Sakha by the expansion of the Tungusic people. MtDNA haplogroups Z1a1b and Z1a3, present in Yukaghirs, Evens and Dolgans, show traces of different and probably more ancient migration(s). Analysis of both haploid loci and autosomal SNP data revealed only minor genetic components shared between Sakha and the extreme Northeast Siberia. Although the major part of West Eurasian maternal and paternal lineages in Sakha could originate from recent admixture with East Europeans, mtDNA haplogroups H8, H20a and HV1a1a, as well as Y-chromosome haplogroup J, more probably reflect an ancient gene flow from West Eurasia through Central Asia and South Siberia.
Conclusions
Our high-resolution phylogenetic dissection of mtDNA and Y-chromosome haplogroups as well as analysis of autosomal SNP data suggests that Sakha was colonized by repeated expansions from South Siberia with minor gene flow from the Lower Amur/Southern Okhotsk region and/or Kamchatka. The minor West Eurasian component in Sakha attests to both recent and ongoing admixture with East Europeans and an ancient gene flow from West Eurasia.
doi:10.1186/1471-2148-13-127
PMCID: PMC3695835  PMID: 23782551
mtDNA; Y chromosome; Autosomal SNPs; Sakha
16.  Genetic evidence supports linguistic affinity of Mlabri - a hunter-gatherer group in Thailand 
BMC Genetics  2010;11:18.
Background
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.
Results
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.
Conclusion
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.
doi:10.1186/1471-2156-11-18
PMCID: PMC2858090  PMID: 20302622
17.  Large-scale mitochondrial DNA analysis in Southeast Asia reveals evolutionary effects of cultural isolation in the multi-ethnic population of Myanmar 
Background
Myanmar is the largest country in mainland Southeast Asia with a population of 55 million people subdivided into more than 100 ethnic groups. Ruled by changing kingdoms and dynasties and lying on the trade route between India and China, Myanmar was influenced by numerous cultures. Since its independence from British occupation, tensions between the ruling Bamar and ethnic minorities increased.
Results
Our aim was to search for genetic footprints of Myanmar’s geographic, historic and sociocultural characteristics and to contribute to the picture of human colonization by describing and dating of new mitochondrial DNA (mtDNA) haplogroups. Therefore, we sequenced the mtDNA control region of 327 unrelated donors and the complete mitochondrial genome of 44 selected individuals according to highest quality standards.
Conclusion
Phylogenetic analyses of the entire mtDNA genomes uncovered eight new haplogroups and three unclassified basal M-lineages. The multi-ethnic population and the complex history of Myanmar were reflected in its mtDNA heterogeneity. Population genetic analyses of Burmese control region sequences combined with population data from neighboring countries revealed that the Myanmar haplogroup distribution showed a typical Southeast Asian pattern, but also Northeast Asian and Indian influences. The population structure of the extraordinarily diverse Bamar differed from that of the Karen people who displayed signs of genetic isolation. Migration analyses indicated a considerable genetic exchange with an overall positive migration balance from Myanmar to neighboring countries. Age estimates of the newly described haplogroups point to the existence of evolutionary windows where climatic and cultural changes gave rise to mitochondrial haplogroup diversification in Asia.
doi:10.1186/1471-2148-14-17
PMCID: PMC3913319  PMID: 24467713
Haplogroup; Complete mtDNA genome; Control region; Population genetics; Migration; Gene flow; Burma; Southeast Asia; Karen; Bamar; Demographic history
18.  Cross Neutralization of Afro-Asian Cobra and Asian Krait Venoms by a Thai Polyvalent Snake Antivenom (Neuro Polyvalent Snake Antivenom) 
Background
Snake envenomation is a serious public health threat in the rural areas of Asian and African countries. To date, the only proven treatment for snake envenomation is antivenom therapy. Cross-neutralization of heterologous venoms by antivenom raised against venoms of closely related species has been reported. The present study examined the cross neutralizing potential of a newly developed polyvalent antivenom, termed Neuro Polyvalent Snake Antivenom (NPAV). NPAV was produced by immunization against 4 Thai elapid venoms.
Principal Findings
In vitro neutralization study using mice showed that NPAV was able to neutralize effectively the lethality of venoms of most common Asiatic cobras (Naja spp.), Ophiophagus hannah and kraits (Bungarus spp.) from Southeast Asia, but only moderately to weakly effective against venoms of Naja from India subcontinent and Africa. Studies with several venoms showed that the in vivo neutralization potency of the NPAV was comparable to the in vitro neutralization potency. NPAV could also fully protect against N. sputatrix venom-induced cardio-respiratory depressant and neuromuscular blocking effects in anesthetized rats, demonstrating that the NPAV could neutralize most of the major lethal toxins in the Naja venom.
Conclusions/Significance
The newly developed polyvalent antivenom NPAV may find potential application in the treatment of elapid bites in Southeast Asia, especially Malaysia, a neighboring nation of Thailand. Nevertheless, the applicability of NPAV in the treatment of cobra and krait envenomations in Southeast Asian victims needs to be confirmed by clinical trials. The cross-neutralization results may contribute to the design of broad-spectrum polyvalent antivenom.
Author Summary
Snake envenomation is a serious public health threat in the rural areas of Asia and Africa. To date, the only proven treatment for snake envenomation is antivenom therapy. Owing to the difficulties in the diagnosis of the biting species, there is a need to develop polyvalent antivenoms that could cross-neutralize venoms of medically important venomous snakes in the various regions. Recently, Thai Red Cross Society from Thailand has developed a new polyvalent antivenom for treatment of cobra and krait venoms. The polyvalent antivenom, termed “Neuro Polyvalent Snake Antivenom (NPAV),” is raised against venoms of two Thai cobras and two Thai kraits. Our results indicated that the polyvalent antivenom can effectively neutralize venoms from many Southeast Asian cobras, kraits and king cobra but is less effective against Indian cobra venoms. Studies using anesthetized rats showed that NPAV can effectively protect against cobra venom-induced cardio-respiratory depressant and neuromuscular blocking effects, confirming that the antivenom can effectively neutralize the major lethal toxins of common cobra venoms. This new antivenom may find potential application in the treatment of elapid bites in Southeast Asia, especially Malaysia, a neighboring nation of Thailand.
doi:10.1371/journal.pntd.0001672
PMCID: PMC3367981  PMID: 22679522
19.  Microsatellite analysis of chloroquine resistance associated alleles and neutral loci reveal genetic structure of Indian Plasmodium falciparum 
Efforts to control malignant malaria caused by Plasmodium falciparum are hampered by the parasite’s acquisition of resistance to antimalarial drugs, e.g., chloroquine. This necessitates evaluating the spread of chloroquine resistance in any malaria-endemic area. India displays highly variable malaria epidemiology and also shares porous international borders with malaria-endemic Southeast Asian countries having multi-drug resistant malaria. Malaria epidemiology in India is believed to be affected by two major factors: high genetic diversity and evolving drug resistance in P. falciparum. How transmission intensity of malaria can influence the genetic structure of chloroquine-resistant P. falciparum population in India is unknown. Here, genetic diversity within and among P. falciparum populations is analyzed with respect to their prevalence and chloroquine resistance observed in 13 different locations in India. Microsatellites developed for P. falciparum, including three putatively neutral and seven microsatellites thought to be under a hitchhiking effect due to chloroquine selection were used. Genetic hitchhiking is observed in five of seven microsatellites flanking the gene responsible for chloroquine resistance. Genetic admixture analysis and F-statistics detected genetically distinct groups in accordance with transmission intensity of different locations and the probable use of chloroquine. A large genetic break between the chloroquine-resistant parasite of the Northeast-East-Island group and Southwest group (FST = 0.253, P<0.001) suggests a long period of isolation or a possibility of different origin between them. A pattern of significant isolation by distance was observed in low transmission areas (r = 0.49, P=0.003, N = 83, Mantel test). An unanticipated pattern of spread of hitchhiking suggests genetic structure for Indian P. falciparum population. Overall, the study suggests that transmission intensity can be an efficient driver for genetic differentiation at both neutral and adaptive loci across India.
doi:10.1016/j.meegid.2013.07.009
PMCID: PMC3799960  PMID: 23871774
Plasmodium falciparum; India; Chloroquine resistance; Hitchhiking; Transmission area; Gene-flow
20.  Genetic population structure of the malaria vector Anopheles baimaii in north-east India using mitochondrial DNA 
Malaria Journal  2012;11:76.
Background
Anopheles baimaii is a primary vector of human malaria in the forest settings of Southeast Asia including the north-eastern region of India. Here, the genetic population structure and the basic population genetic parameters of An. baimaii in north-east India were estimated using DNA sequences of the mitochondrial cytochrome oxidase sub unit II (COII) gene.
Methods
Anopheles baimaii were collected from 26 geo-referenced locations across the seven north-east Indian states and the COII gene was sequenced from 176 individuals across these sites. Fifty-seven COII sequences of An. baimaii from six locations in Bangladesh, Myanmar and Thailand from a previous study were added to this dataset. Altogether, 233 sequences were grouped into eight population groups, to facilitate analyses of genetic diversity, population structure and population history.
Results
A star-shaped median joining haplotype network, unimodal mismatch distribution and significantly negative neutrality tests indicated population expansion in An. baimaii with the start of expansion estimated to be ~0.243 million years before present (MYBP) in north-east India. The populations of An. baimaii from north-east India had the highest haplotype and nucleotide diversity with all other populations having a subset of this diversity, likely as the result of range expansion from north-east India. The north-east Indian populations were genetically distinct from those in Bangladesh, Myanmar and Thailand, indicating that mountains, such as the Arakan mountain range between north-east India and Myanmar, are a significant barrier to gene flow. Within north-east India, there was no genetic differentiation among populations with the exception of the Central 2 population in the Barail hills area that was significantly differentiated from other populations.
Conclusions
The high genetic distinctiveness of the Central 2 population in the Barail hills area of the north-east India should be confirmed and its epidemiological significance further investigated. The lack of genetic population structure in the other north-east Indian populations likely reflects large population sizes of An. baimaii that, historically, were able to disperse through continuous forest habitats in the north-east India. Additional markers and analytical approaches are required to determine if recent deforestation is now preventing ongoing gene flow. Until such information is acquired, An. baimaii in north-east India should be treated as a single unit for the implementation of vector control measures.
doi:10.1186/1475-2875-11-76
PMCID: PMC3337289  PMID: 22429500
Anopheles baimaii; Cytochrome oxidase II; Southeast Asia; Malaria vector; North-east India; Population genetics
21.  Genetic structure of wild boar (Sus scrofa) populations from East Asia based on microsatellite loci analyses 
BMC Genetics  2014;15:85.
Background
Wild boar, Sus scrofa, is an extant wild ancestor of the domestic pig as an agro-economically important mammal. Wild boar has a worldwide distribution with its geographic origin in Southeast Asia, but genetic diversity and genetic structure of wild boar in East Asia are poorly understood. To characterize the pattern and amount of genetic variation and population structure of wild boar in East Asia, we genotyped and analyzed microsatellite loci for a total of 238 wild boar specimens from ten locations across six countries in East and Southeast Asia.
Results
Our data indicated that wild boar populations in East Asia are genetically diverse and structured, showing a significant correlation of genetic distance with geographic distance and implying a low level of gene flow at a regional scale. Bayesian-based clustering analysis was indicative of seven inferred genetic clusters in which wild boars in East Asia are geographically structured. The level of genetic diversity was relatively high in wild boars from Southeast Asia, compared with those from Northeast Asia. This gradient pattern of genetic diversity is consistent with an assumed ancestral population of wild boar in Southeast Asia. Genetic evidences from a relationship tree and structure analysis suggest that wild boar in Jeju Island, South Korea have a distinct genetic background from those in mainland Korea.
Conclusions
Our results reveal a diverse pattern of genetic diversity and the existence of genetic differentiation among wild boar populations inhabiting East Asia. This study highlights the potential contribution of genetic variation of wild boar to the high genetic diversity of local domestic pigs during domestication in East Asia.
doi:10.1186/1471-2156-15-85
PMCID: PMC4112609  PMID: 25034725
Microsatellites; East Asia; Genetic diversity; Genetic structure; Wild boar
22.  Plasmodium vivax Diversity and Population Structure across Four Continents 
PLoS Neglected Tropical Diseases  2015;9(6):e0003872.
Plasmodium vivax is the geographically most widespread human malaria parasite. To analyze patterns of microsatellite diversity and population structure across countries of different transmission intensity, genotyping data from 11 microsatellite markers was either generated or compiled from 841 isolates from four continents collected in 1999–2008. Diversity was highest in South-East Asia (mean allelic richness 10.0–12.8), intermediate in the South Pacific (8.1–9.9) Madagascar and Sudan (7.9–8.4), and lowest in South America and Central Asia (5.5–7.2). A reduced panel of only 3 markers was sufficient to identify approx. 90% of all haplotypes in South Pacific, African and SE-Asian populations, but only 60–80% in Latin American populations, suggesting that typing of 2–6 markers, depending on the level of endemicity, is sufficient for epidemiological studies. Clustering analysis showed distinct clusters in Peru and Brazil, but little sub-structuring was observed within Africa, SE-Asia or the South Pacific. Isolates from Uzbekistan were exceptional, as a near-clonal parasite population was observed that was clearly separated from all other populations (FST>0.2). Outside Central Asia FST values were highest (0.11–0.16) between South American and all other populations, and lowest (0.04–0.07) between populations from South-East Asia and the South Pacific. These comparisons between P. vivax populations from four continents indicated that not only transmission intensity, but also geographical isolation affect diversity and population structure. However, the high effective population size results in slow changes of these parameters. This persistency must be taken into account when assessing the impact of control programs on the genetic structure of parasite populations.
Author Summary
Plasmodium vivax is the predominant malaria parasite in Latin America, Asia and the South Pacific. Different factors are expected to shape diversity and population structure across continents, e.g. transmission intensity which is much lower in South America as compared to Southeast-Asia and the South Pacific, or geographical isolation of P. vivax populations in the South Pacific. We have compiled data from 841 isolates from South and Central America, Africa, Central Asia, Southeast-Asia and the South Pacific typed with a panel of 11 microsatellite markers. Diversity was highest in Southeast-Asia, where transmission is intermediate-high and migration of infected hosts is high, and lowest in South America and Central Asia where malaria transmission is low and focal. Reducing the panel of microsatellites showed that 2–6 markers are sufficient for genotyping for most drug trials and epidemiological studies, as these markers can identify >90% of all haplotypes. Parasites clustered according to continental origin, with high population differentiation between South American and Central Asian populations and the other populations, and lowest differences between Southeast-Asia and the South Pacific. Current attempts to reduce malaria transmission might change this pattern, but only after transmission is reduced for an extended period of time.
doi:10.1371/journal.pntd.0003872
PMCID: PMC4488360  PMID: 26125189
23.  Real-Time PCR Assay for Rapid Detection and Analysis of PfCRT Haplotypes of Chloroquine-Resistant Plasmodium falciparum Isolates from India▿  
Journal of Clinical Microbiology  2007;45(9):2889-2893.
Chloroquine-resistant Plasmodium falciparum (CRPF) malaria isolates in Southeast Asia and sub-Saharan Africa share the same Plasmodium falciparum chloroquine resistance transporter (PfCRT) haplotype (CVIET; amino acids 72 to 76). It is believed that CRPF malaria emerged in Southeast Asia and spread to sub-Saharan Africa via the Indian subcontinent. Based on this assumption, we hypothesized that CRPF isolates in India should possess the same drug resistance haplotype (PfCRT haplotype CVIET) as P. falciparum isolates in Southeast Asia and Africa and that the prevalence of CRPF may be higher and more widespread in India than appreciated. To test this postulate, we utilized a standardized real-time PCR assay to assess the prevalence and distribution of PfCRT haplotypes in P. falciparum isolates (n = 406) collected from Western, Central, and Eastern states in India and compared them to isolates from South America and Africa. Based on the proportion of isolates possessing the molecular marker K76T, the prevalence of chloroquine resistance was high in all five regions of India studied (91%), as well as in Uganda (98%) and Suriname (100%). All isolates from Suriname contained the chloroquine-resistant SVMNT haplotype typical of South American isolates, and 98% of isolates from Uganda possessed the chloroquine-resistant CVIET haplotype characteristic of Southeast Asian/African strains. However, of 246 P. falciparum isolates from across India that contained the molecular marker for chloroquine resistance, 81% contained the SVMNT haplotype. In conclusion, the prevalence of CRPF malaria was high in geographically dispersed regions of India, and the primary haplotype observed, SVMNT, did not support a presumed geographic spread from contiguous Southeast Asia.
doi:10.1128/JCM.02291-06
PMCID: PMC2045286  PMID: 17609321
24.  Clade C HIV-1 isolates circulating in Southern Africa exhibit a greater frequency of dicysteine motif-containing Tat variants than those in Southeast Asia and cause increased neurovirulence 
Retrovirology  2013;10:61.
Background
HIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. However, recent studies report a higher prevalence of HAD in South Africa, Zambia and Botswana, where HIV-1C infections predominate. Therefore, we examined whether Southern African HIV-1C is genetically distinct and investigated its neurovirulence. HIV-1 Tat protein is a viral determinant of neurocognitive dysfunction. Therefore, we focused our study on the variations seen in tat gene and its contribution to HIV associated neuropathogenesis.
Results
A phylogenetic analysis of tat sequences of Southern African (South Africa and Zambia) HIV isolates with those from the geographically distant Southeast Asian (India and Bangladesh) isolates revealed that Southern African tat sequences are distinct from Southeast Asian isolates. The proportion of HIV − 1C variants with an intact dicysteine motif in Tat protein (C30C31) was significantly higher in the Southern African countries compared to Southeast Asia and broadly paralleled the high incidence of HAD in these countries. Neuropathogenic potential of a Southern African HIV-1C isolate (from Zambia; HIV-1C1084i), a HIV-1C isolate (HIV-1IndieC1) from Southeast Asia and a HIV-1B isolate (HIV-1ADA) from the US were tested using in vitro assays to measure neurovirulence and a SCID mouse HIV encephalitis model to measure cognitive deficits. In vitro assays revealed that the Southern African isolate, HIV-1C1084i exhibited increased monocyte chemotaxis and greater neurotoxicity compared to Southeast Asian HIV-1C. In neurocognitive tests, SCID mice injected with MDM infected with Southern African HIV-1C1084i showed greater cognitive dysfunction similar to HIV-1B but much higher than those exposed to Southeast Asian HIV − 1C.
Conclusions
We report here, for the first time, that HIV-1C from Southern African countries is genetically distinct from Southeast Asian HIV-1C and that it exhibits a high frequency of variants with dicysteine motif in a key neurotoxic HIV protein, Tat. Our results indicate that Tat dicysteine motif determines neurovirulence. If confirmed in population studies, it may be possible to predict neurocognitive outcomes of individuals infected with HIV-1C by genotyping Tat.
doi:10.1186/1742-4690-10-61
PMCID: PMC3686704  PMID: 23758766
Clade C HIV-1; Subtype C HIV-1; HIV-1 Tat; Tat dicysteine; Neuropathogenesis; SCID-HIVE mouse model; HIV-1 Tat C31S polymorphism; Neuroaids; HIV dementia
25.  Most of the extant mtDNA boundaries in South and Southwest Asia were likely shaped during the initial settlement of Eurasia by anatomically modern humans 
BMC Genetics  2004;5:26.
Background
Recent advances in the understanding of the maternal and paternal heritage of south and southwest Asian populations have highlighted their role in the colonization of Eurasia by anatomically modern humans. Further understanding requires a deeper insight into the topology of the branches of the Indian mtDNA phylogenetic tree, which should be contextualized within the phylogeography of the neighboring regional mtDNA variation. Accordingly, we have analyzed mtDNA control and coding region variation in 796 Indian (including both tribal and caste populations from different parts of India) and 436 Iranian mtDNAs. The results were integrated and analyzed together with published data from South, Southeast Asia and West Eurasia.
Results
Four new Indian-specific haplogroup M sub-clades were defined. These, in combination with two previously described haplogroups, encompass approximately one third of the haplogroup M mtDNAs in India. Their phylogeography and spread among different linguistic phyla and social strata was investigated in detail. Furthermore, the analysis of the Iranian mtDNA pool revealed patterns of limited reciprocal gene flow between Iran and the Indian sub-continent and allowed the identification of different assemblies of shared mtDNA sub-clades.
Conclusions
Since the initial peopling of South and West Asia by anatomically modern humans, when this region may well have provided the initial settlers who colonized much of the rest of Eurasia, the gene flow in and out of India of the maternally transmitted mtDNA has been surprisingly limited. Specifically, our analysis of the mtDNA haplogroups, which are shared between Indian and Iranian populations and exhibit coalescence ages corresponding to around the early Upper Paleolithic, indicates that they are present in India largely as Indian-specific sub-lineages. In contrast, other ancient Indian-specific variants of M and R are very rare outside the sub-continent.
doi:10.1186/1471-2156-5-26
PMCID: PMC516768  PMID: 15339343

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