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.