The matrilineal ancestry of Nepali populations.

The Tibetan plateau and high mountain ranges of Nepal are one of the challenging geographical regions inhabited by modern humans. While much of the ethnographic and population-based genetic studies were carried out to investigate the Tibetan and Sherpa highlanders, little is known about the demographic processes that enabled the colonization of the hilly areas of Nepal. Thus, the present study aimed to investigate the past demographic events that shaped the extant Nepalese genetic diversity using mitochondrial DNA (mtDNA) variations from ethnic Nepalese groups. We have analyzed mtDNA sequences of 999 Nepalese and compared data with 38,622 published mtDNA sequences from rest of the world. Our analysis revealed that the genomic landscapes of prehistoric Himalayan settlers of Nepal were similar to that of the low-altitude extant Nepalese (LAN), especially Newar and Magar population groups, but differ from contemporary high-altitude Sherpas. LAN might have derived their East Eurasian ancestry mainly from low-altitude Tibeto-Burmans, who likely have migrated from East Asia and assimilated across the Eastern Himalayas extended from the Eastern Nepal to the North-East of India, Bhutan, Tibet and Northern Myanmar. We also identified a clear genetic sub-structure across different ethnic groups of Nepal based on mtDNA haplogroups and ectodysplasin-A receptor (EDAR) gene polymorphism. Our comprehensive high-resolution mtDNA-based genetic study of Tibeto-Burman communities reconstructs the maternal origins of prehistoric Himalayan populations and sheds light on migration events that have brought most of the East Eurasian ancestry to the present-day Nepalese population.

Signatures of high altitude adaptation in Tibeto-Burman tribes of the Darjeeling Hill Region.

OBJECTIVES: The long-term isolation, endogamy practices, and environmental adaptations have shaped the enormous human diversity in India. The genetic and morphological variations in mainland Indians are well studied. However, the data on the Indian Himalayan populations are scattered. Thus, the present study attempts to understand variations in the selected parameter among four Tibeto-Burman speaking ethnic tribal populations from the Darjeeling Hill Region (DHR) in the Eastern Himalaya Biodiversity Hotspot region of India. METHODS: A total of 178 healthy male individuals (Lepcha 98, Sherpa 31, Bhutia 27, and Tibetans 22) living at an altitudinal range of 1467-2258 m above the sea level were studied for the 10 parameters namely, weight (kg), height (cm), body mass index (BMI) (kg/m2 ) systolic and diastolic pressure (mm of Hg), pulse rate (per minute), saturation of peripheral oxygen (SPO2 ) (%), hemoglobin (g/dl), hematocrit (HCT) (%), and blood glucose (mg/dl). The data was statistically analyzed using analysis of variance and multiple linear regression methods. RESULTS: Our analysis revealed comparatively lower hemoglobin and HCT levels, and higher systolic and diastolic blood pressure in the Sherpas followed by the Tibetans. This may be reflecting the persistence of high-altitude adaptation signatures even in lowlands. Interestingly, the Tibetans differed significantly from other populations in terms of their higher body weight, height, and BMI. CONCLUSION: Thus, our study showed the persistence of high altitude signatures in Tibetans and Sherpa inhabited the DHR. Additionally, we also observed significant differences in the anthropometric and physiological parameters among the Tibeto-Burman populations of the DHR.

COVID-19: Impact on linguistic and genetic isolates of India.

The rapid expansion of coronavirus SARS-CoV-2 has impacted various ethnic groups all over the world. The burden of infectious diseases including COVID-19 are generally reported to be higher for the Indigenous people. The historical knowledge have also suggested that the indigenous populations suffer more than the general populations in the pandemic. Recently, it has been reported that the indigenous groups of Brazil have been massively affected by COVID-19. Series of studies have shown that many of the indigenous communities reached at the verge of extinction due to this pandemic. Importantly, South Asia also has several indigenous and smaller communities, that are living in isolation. Till date, despite the two consecutive waves in India, there is no report on the impact of COVID-19 for indigenous tribes. Since smaller populations experiencing drift may have greater risk of such pandemic, we have analysed Runs of Homozygosity (ROH) among South Asian populations and identified several populations with longer homozygous segments. The longer runs of homozygosity at certain genomic regions may increases the susceptibility for COVID-19. Thus, we suggest extreme careful management of this pandemic among isolated populations of South Asia.

Reconstructing the demographic history of the Himalayan and adjoining populations.

The rugged topography of the Himalayan region has hindered large-scale human migrations, population admixture and assimilation. Such complexity in geographical structure might have facilitated the existence of several small isolated communities in this region. We have genotyped about 850,000 autosomal markers among 35 individuals belonging to the four major populations inhabiting the Himalaya and adjoining regions. In addition, we have genotyped 794 individuals belonging to 16 ethnic groups from the same region, for uniparental (mitochondrial and Y chromosomal DNA) markers. Our results in the light of various statistical analyses suggest a closer link of the Himalayan and adjoining populations to East Asia than their immediate geographical neighbours in South Asia. Allele frequency-based analyses likely support the existence of a specific ancestry component in the Himalayan and adjoining populations. The admixture time estimate suggests a recent westward migration of populations living to the East of the Himalaya. Furthermore, the uniparental marker analysis among the Himalayan and adjoining populations reveal the presence of East, Southeast and South Asian genetic signatures. Interestingly, we observed an antagonistic association of Y chromosomal haplogroups O3 and D clines with the longitudinal distance. Thus, we summarise that studying the Himalayan and adjoining populations is essential for a comprehensive reconstruction of the human evolutionary and ethnolinguistic history of eastern Eurasia.

The paternal ancestry of Uttarakhand does not imitate the classical caste system of India.

Although, there have been rigorous research on the Indian caste system by several disciplines, it is still one of the most controversial socioscientific topic. Previous genetic studies on the subcontinent have supported a classical hierarchal sharing of genetic component by various castes of India. In the present study, we have used high-resolution mtDNA and Y chromosomal markers to characterize the genetic structuring of the Uttarakhand populations in the context of neighboring regions. Furthermore, we have tested whether the genetic structuring of caste populations at different social levels of this region, follow the classical chaturvarna system. Interestingly, we found that this region showed a high level of variation for East Eurasian ancestry in both maternal and paternal lines of descent. Moreover, the intrapopulation comparison showed a high level of heterogeneity, likely because of different caste hierarchy, interpolated on asymmetric admixture of populations inhabiting on both sides of the Himalayas.

The light skin allele of SLC24A5 in South Asians and Europeans shares identity by descent.

Skin pigmentation is one of the most variable phenotypic traits in humans. A non-synonymous substitution (rs1426654) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians. A previous genome-wide association study carried out in a heterogeneous sample of UK immigrants of South Asian descent suggested that this gene also contributes significantly to skin pigmentation variation among South Asians. In the present study, we have quantitatively assessed skin pigmentation for a largely homogeneous cohort of 1228 individuals from the Southern region of the Indian subcontinent. Our data confirm significant association of rs1426654 SNP with skin pigmentation, explaining about 27% of total phenotypic variation in the cohort studied. Our extensive survey of the polymorphism in 1573 individuals from 54 ethnic populations across the Indian subcontinent reveals wide presence of the derived-A allele, although the frequencies vary substantially among populations. We also show that the geospatial pattern of this allele is complex, but most importantly, reflects strong influence of language, geography and demographic history of the populations. Sequencing 11.74 kb of SLC24A5 in 95 individuals worldwide reveals that the rs1426654-A alleles in South Asian and West Eurasian populations are monophyletic and occur on the background of a common haplotype that is characterized by low genetic diversity. We date the coalescence of the light skin associated allele at 22-28 KYA. Both our sequence and genome-wide genotype data confirm that this gene has been a target for positive selection among Europeans. However, the latter also shows additional evidence of selection in populations of the Middle East, Central Asia, Pakistan and North India but not in South India.

Indian Siddis: African descendants with Indian admixture.

The Siddis (Afro-Indians) are a tribal population whose members live in coastal Karnataka, Gujarat, and in some parts of Andhra Pradesh. Historical records indicate that the Portuguese brought the Siddis to India from Africa about 300-500 years ago; however, there is little information about their more precise ancestral origins. Here, we perform a genome-wide survey to understand the population history of the Siddis. Using hundreds of thousands of autosomal markers, we show that they have inherited ancestry from Africans, Indians, and possibly Europeans (Portuguese). Additionally, analyses of the uniparental (Y-chromosomal and mitochondrial DNA) markers indicate that the Siddis trace their ancestry to Bantu speakers from sub-Saharan Africa. We estimate that the admixture between the African ancestors of the Siddis and neighboring South Asian groups probably occurred in the past eight generations (∼200 years ago), consistent with historical records.

EPHX1 gene polymorphisms in alcohol dependence and their distribution among the Indian populations.

BACKGROUND: The microsomal epoxide hydrolase is a phase II enzyme of the biotransformation. The human epoxide hydrolase 1 (EPHX1) gene lies in the chromosomal region 1q42.1 and exhibits polymorphism. Two single nucleotide polymorphisms (SNPs) have been described in the coding region of the EPHX1 gene that produces two protein variants. SUBJECTS AND METHODS: A total of 604 samples belonging to 13 Indian populations were included in this study. Based on the DSM-IV criteria, 184 individuals from Kota population were classified into alcoholism cases (100) and controls (84). Genotypes of Tyr113His and His139Arg polymorphisms in the EPHX1 gene were determined using PCR and sequencing. Associations were tested using Pearson's χ(2) test and haplotype analyses. RESULTS: We found significant association between EPHX1 gene Tyr113His polymorphism and alcoholism in the Kota population (T vs. C: OR = .615, 95% CI = .399-.949, p = .027; TT vs. CC + CT: OR = .536, 95% CI = .297-.969, p = .038). The very slow activity haplotype CA (113His-139His) was also found to be associated with alcohol dependence (p = .048). Analysis of additional populations demonstrated that the Tyr113His polymorphism significantly deviated from Hardy-Weinberg equilibrium in four populations but only one population deviated for the His139Arg locus. All populations shared the four possible two-site haplotypes. Linkage disequilibrium between these two loci was not significant in any of the population studied. CONCLUSION: EPHX1 gene polymorphisms and haplotypes are associated with an increased risk for alcoholism in the Kota population. This is the first report from India that will serve as a template for future investigations of the prevalence of EPHX1 alleles in association with various clinical entities.

Vaccine hesitancy for coronavirus SARS-CoV-2 in Varanasi India.

With the rollout of the world's largest vaccine drive for SARS-CoV-2 by the Government of India on January 16 2021, India had targeted to vaccinate its entire population by the end of 2021. Struggling with vaccine procurement and production earlier, India overcome these hurdles, but the Indian population still did not seem to be mobilizing swiftly toward vaccination centers. The severe second wave has slowed the vaccination pace and was also one of the major contributing factors to vaccine hesitancy. To understand the nature of vaccine hesitancy and its underlying factors, we conducted extensive online and offline surveys in Varanasi and adjoining regions using structured questions. Most respondents were students (0.633). However, respondents from other occupations, such as government officials (0.10), have also participated in the study. Interestingly, most people (0.75) relied on fake news and did not take COVID-19 seriously. Most importantly, we noticed that a substantial proportion of respondents (relative frequency 0.151; mean age 24.8 years) reported that they were still not interested in vaccination. We observed a significant association between vaccine hesitancy and socioeconomic status (χ2 = 307.6, p < 0.001). However, we failed to detect any association between vaccine hesitancy and gender (χ2 = 0.007, p > 0.5). People who have neither been vaccinated nor have ever been infected may become the medium for spreading the virus and creating new variants, which may lead to the vaccine-resistant variant. We expect this extensive survey to help the Government upgrade their vaccination policies for COVID-19 in North India.

Most frequent South Asian haplotypes of ACE2 share identity by descent with East Eurasian populations.

It was shown that the human Angiotensin-converting enzyme 2 (ACE2) is the receptor of recent coronavirus SARS-CoV-2, and variation in this gene may affect the susceptibility of a population. Therefore, we have analysed the sequence data of ACE2 among 393 samples worldwide, focusing on South Asia. Genetically, South Asians are more related to West Eurasian populations rather than to East Eurasians. In the present analyses of ACE2, we observed that the majority of South Asian haplotypes are closer to East Eurasians rather than to West Eurasians. The phylogenetic analysis suggested that the South Asian haplotypes shared with East Eurasians involved two unique event polymorphisms (rs4646120 and rs2285666). In contrast with the European/American populations, both of the SNPs have largely similar frequencies for East Eurasians and South Asians, Therefore, it is likely that among the South Asians, host susceptibility to the novel coronavirus SARS-CoV-2 will be more similar to that of East Eurasians rather than to that of Europeans.

Genetic and linguistic non-correspondence suggests evidence for collective social climbing in the Kol tribe of South Asia.

Both classical and recent genetic studies have unanimously concluded that the genetic landscape of South Asia is unique. At long distances the 'isolation-by-distance' model appears to correspond well with the genetic data, whereas at short distances several other factors, including the caste, have been shown to be strong determinant factors. In addition with these, tribal populations speaking various languages add yet another layer of genetic complexity. The Kol are the third most populous tribal population in India, comprising communities speaking Austroasiatic languages of the Northern Munda branch. Yet, the Kol have not hitherto undergone in-depth genetic analysis. In the present study, we have analysed two Kol groups of central and western India for hundreds thousands of autosomal and several mitochondrial DNA makers to infer their fine genetic structure and affinities to other Eurasian populations. In contrast, with their known linguistic affinity, the Kol share their more recent common ancestry with the Indo-European and Dravidian speaking populations. The geographic-genetic neighbour tests at both the temporal and spatial levels have suggested some degree of excess allele sharing of Kol1 with Kol2, thereby indicating their common stock. Our extensive analysis on the Kol ethnic group shows South Asia to be a living genetics lab, where real-time tests can be performed on existing hypotheses.

Mitochondrial genome variations in idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. The aim of this study was to assess the role of mitochondrial DNA (mtDNA) variations and haplogroups in Indian DCM patients. Whole mtDNA analysis of 221 DCM patients revealed 48 novel, 42 disease-associated and 97 private variations. The frequency of reported variations associated with hearing impairment, DEAF, SNHL and LHON are significantly high in DCM patients than controls. Haplogroups H and HV were over represented in DCM than controls. Functional analysis of two private variations (m.8812A>G & m.10320G>A) showed decrease in mitochondrial functions, suggesting the role of mtDNA variations in DCM.

Reconstructing the population history of the largest tribe of India: the Dravidian speaking Gond.

The Gond comprise the largest tribal group of India with a population exceeding 12 million. Linguistically, the Gond belong to the Gondi-Manda subgroup of the South Central branch of the Dravidian language family. Ethnographers, anthropologists and linguists entertain mutually incompatible hypotheses on their origin. Genetic studies of these people have thus far suffered from the low resolution of the genetic data or the limited number of samples. Therefore, to gain a more comprehensive view on ancient ancestry and genetic affinities of the Gond with the neighbouring populations speaking Indo-European, Dravidian and Austroasiatic languages, we have studied four geographically distinct groups of Gond using high-resolution data. All the Gond groups share a common ancestry with a certain degree of isolation and differentiation. Our allele frequency and haplotype-based analyses reveal that the Gond share substantial genetic ancestry with the Indian Austroasiatic (ie, Munda) groups, rather than with the other Dravidian groups to whom they are most closely related linguistically.

Reconstructing the population history of the largest tribe of India: the Dravidian speaking Gond.

This corrects the article DOI: 10.1038/ejhg.2016.198.

"Like sugar in milk": reconstructing the genetic history of the Parsi population.

BACKGROUND: The Parsis are one of the smallest religious communities in the world. To understand the population structure and demographic history of this group in detail, we analyzed Indian and Pakistani Parsi populations using high-resolution genetic variation data on autosomal and uniparental loci (Y-chromosomal and mitochondrial DNA). Additionally, we also assayed mitochondrial DNA polymorphisms among ancient Parsi DNA samples excavated from Sanjan, in present day Gujarat, the place of their original settlement in India. RESULTS: Among present-day populations, the Parsis are genetically closest to Iranian and the Caucasus populations rather than their South Asian neighbors. They also share the highest number of haplotypes with present-day Iranians and we estimate that the admixture of the Parsis with Indian populations occurred ~1,200 years ago. Enriched homozygosity in the Parsi reflects their recent isolation and inbreeding. We also observed 48% South-Asian-specific mitochondrial lineages among the ancient samples, which might have resulted from the assimilation of local females during the initial settlement. Finally, we show that Parsis are genetically closer to Neolithic Iranians than to modern Iranians, who have witnessed a more recent wave of admixture from the Near East. CONCLUSIONS: Our results are consistent with the historically-recorded migration of the Parsi populations to South Asia in the 7th century and in agreement with their assimilation into the Indian sub-continent's population and cultural milieu "like sugar in milk". Moreover, in a wider context our results support a major demographic transition in West Asia due to the Islamic conquest.

Origin and spread of human mitochondrial DNA haplogroup U7.

Human mitochondrial DNA haplogroup U is among the initial maternal founders in Southwest Asia and Europe and one that best indicates matrilineal genetic continuity between late Pleistocene hunter-gatherer groups and present-day populations of Europe. While most haplogroup U subclades are older than 30 thousand years, the comparatively recent coalescence time of the extant variation of haplogroup U7 (~16-19 thousand years ago) suggests that its current distribution is the consequence of more recent dispersal events, despite its wide geographical range across Europe, the Near East and South Asia. Here we report 267 new U7 mitogenomes that - analysed alongside 100 published ones - enable us to discern at least two distinct temporal phases of dispersal, both of which most likely emanated from the Near East. The earlier one began prior to the Holocene (~11.5 thousand years ago) towards South Asia, while the later dispersal took place more recently towards Mediterranean Europe during the Neolithic (~8 thousand years ago). These findings imply that the carriers of haplogroup U7 spread to South Asia and Europe before the suggested Bronze Age expansion of Indo-European languages from the Pontic-Caspian Steppe region.

Genetic affinities of the Jewish populations of India.

Due to the lack of written records or inscription, the origin and affiliation of Indian Jewish populations with other world populations remain contentious. Previous genetic studies have found evidence for a minor shared ancestry of Indian Jewish with Middle Eastern (Jewish) populations. However, these studies (relied on limited individuals), haven't explored the detailed temporal and spatial admixture process of Indian Jewish populations with the local Indian populations. Here, using large sample size with combination of high resolution biparental (autosomal) and uniparental markers (Y chromosome and mitochondrial DNA), we reconstructed genetic history of Indian Jewish by investigating the patterns of genetic diversity. Consistent with the previous observations, we detected minor Middle Eastern specific ancestry component among Indian Jewish communities, but virtually negligible in their local neighbouring Indian populations. The temporal test of admixture suggested that the first admixture of migrant Jewish populations from Middle East to South India (Cochin) occurred during fifth century. Overall, we concluded that the Jewish migration and admixture in India left a record in their genomes, which can link them to the 'Jewish Diaspora'.

Unravelling the distinct strains of Tharu ancestry.

The northern region of the Indian subcontinent is a vast landscape interlaced by diverse ecologies, for example, the Gangetic Plain and the Himalayas. A great number of ethnic groups are found there, displaying a multitude of languages and cultures. The Tharu is one of the largest and most linguistically diverse of such groups, scattered across the Tarai region of Nepal and bordering Indian states. Their origins are uncertain. Hypotheses have been advanced postulating shared ancestry with Austroasiatic, or Tibeto-Burman-speaking populations as well as aboriginal roots in the Tarai. Several Tharu groups speak a variety of Indo-Aryan languages, but have traditionally been described by ethnographers as representing East Asian phenotype. Their ancestry and intra-population diversity has previously been tested only for haploid (mitochondrial DNA and Y-chromosome) markers in a small portion of the population. This study presents the first systematic genetic survey of the Tharu from both Nepal and two Indian states of Uttarakhand and Uttar Pradesh, using genome-wide SNPs and haploid markers. We show that the Tharu have dual genetic ancestry as up to one-half of their gene pool is of East Asian origin. Within the South Asian proportion of the Tharu genetic ancestry, we see vestiges of their common origin in the north of the South Asian Subcontinent manifested by mitochondrial DNA haplogroup M43.

Mitochondrial DNA variations in Madras motor neuron disease.

Although the Madras motor neuron disease (MMND) was found three decades ago, its genetic basis has not been elucidated, so far. The symptom at onset was impaired hearing, upper limb weakness and atrophy. Since some clinical features of MMND overlap with mitochondrial disorders, we analyzed the complete mitochondrial genome of 45 MMND patients and found 396 variations, including 13 disease-associated, 2 mt-tRNA and 33 non-synonymous (16 MT-ND, 10 MT-CO, 3 MT-CYB and 4 MT-ATPase). A rare variant (m.8302A>G) in mt-tRNA(Leu) was found in three patients. We predict that these variation(s) may influence the disease pathogenesis along with some unknown factor(s).