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The central region of India is incredibly rich in tribal heritage. It is the most frequent Indian state in terms of tribal population. Understanding the genetic history of the tribal population of India may add detailed information about various demographic processes, including social upliftment. However, to understand these microevolutionary processes, high-resolution genetic analysis is warranted. Therefore, we have used cutting-edge Next-generation sequencing (NGS) techniques and sequenced the mitogenomes of 25 random samples from two major (Gond and Kanwar) tribal populations for complete mitogenome analysis. We aimed to understand the initial peopling of Chhattisgarh from a maternal perspective. The complete genome sequencing enabled us to identify several novel sub-haplogroups. Our results suggested an early expansion and proliferation of maternal ancestry rooted in the time of initial settlement of the subcontinent, which has reached near saturation during 25-30Kya. At the background of founding lineages M and N, we identified maternal haplogroups M2, R5 and U2 as three basal founding haplogroups of this region. Overall, we suggest a high effective (Ne) maternal population in Central India during 25Kya, sustained during the Last Glacial Maximus(LGM).

Background SARS CoV-2, the causative agent for the ongoing COVID-19 pandemic, enters the host cell by activating the ACE2 receptor with the help of two proteases, i.e., Furin and TMPRSS2. Therefore, variations in these genes may account for differential susceptibility and severity between populations. Our previous studies have shown that ACE2 and TMPRSS2 gene variants are essential in understanding COVID-19 susceptibility among Indian populations. However, there is a knowledge gap regarding Furin gene variants and their phylogenetic structure among diverse Indian and South Asian ethnic groups and their impact on disease vulnerability, which needs to be investigated. Material and methods Considering the role of the Furin gene in the pathogenesis of SARS-CoV-2. We have used 450 samples from diverse Indian states and performed linear regression to analyse the Furin gene variant's allele frequency with COVID-19 CFR that could be epidemiologically associated with disease severity outcomes among populations. Associated genetic variants were further evaluated for their expression and regulatory potential through various Insilco analyses. Additionally, we examined the Furin gene architecture using next-generation sequencing (NGS) data from 393 diverse global samples, with a particular emphasis on South Asia, to investigate its phylogenetic makeup and the distribution of haplotypes among distinct global populations. Results We found a significant positive association for the rs1981458 with COVID-19 CFR among diverse Indian populations. Further QTL and other regulatory analyses showed various significant associations and positive regulatory roles of this SNP and Furin gene, mainly in Immune cells and virus infection process, highlighting their role in host immunity and viral assembly and processing. The Furin protein-protein interaction suggested that COVID-19 may contribute to Pulmonary arterial hypertension via a typical inflammation mechanism. The phylogenetic architecture of the Furin gene demonstrated a closer genetic affinity between West Eurasian and South Asians. Therefore, it is worth proposing that in the context of the Furin gene, the COVID-19 susceptibility of South Asians will be more similar to the West Eurasian population. Our previous studies on the ACE2 and TMPRSS2 genes showed a contrasting genetic affinity of South Asian with East Eurasians and West Eurasians, respectively. Therefore, we modelled COVID-19 susceptibility for susceptibility of South Asia in between these two major ancestries with an inclination towards West Eurasians. Conclusion In conclusion, this study, for the first time, concluded the role of rs1981458 in COVID-19 severity among the Indian population and outlined its regulatory potential in COVID-19 and genetic structure and susceptibility for COVID-19 susceptibility of South Asia is inclined to West Eurasian population. We believe this insight may well be utilised as a genetic biomarker to identify vulnerable populations, which might be directly relevant for developing policies and allocating resources more effectively during an epidemic.

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.

The phylogenetic analysis of Y chromosomal haplogroup O2a-M95 was crucial to determine the nested structure of South Asian branches within the larger tree, predominantly present in East and Southeast Asia. However, it had previously been unclear that how many founders brought the haplogroup O2a-M95 to South Asia. On the basis of the updated Y chromosomal tree for haplogroup O2a-M95, we analysed 1437 male samples from South Asia for various novel downstream markers, carefully selected from the extant phylogenetic tree. With this increased resolution of genetic markers, we were able to identify at least three founders downstream to haplogroup O2a-M95, who are likely to have been associated with the dispersal of Austroasiatic languages to South Asia. The fourth founder was exclusively present amongst Tibeto-Burman speakers of Manipur and Bangladesh. In sum, our new results suggest the arrival of Austroasiatic languages in South Asia during last 5000 years.

After the spill to humans, in the timeline of SARS-CoV-2, several positively selected variants have emerged. A phylogeographic study on these variants can reveal their spatial and temporal distribution. In December 2020, the alpha variant of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which has been designated as a variant of concern (VOC) by WHO, was discovered in the southeastern United Kingdom (UK). Slowly, it expanded across India, with a considerable number of cases, particularly in North India. The study focuses on determining the prevalence and expansion of the alpha variants in various parts of India. The genetic diversity estimation helped us understand various evolutionary forces that have shaped the spatial distribution of this variant during the peak. Overall, our study paves the way to understand the evolution and expansion of a virus variant.

With the roll-out of world’s largest vaccine drive for Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) by Government of India on January 16 2021, India has targeted to vaccinate its entire population by the end of year 2021. Struggling with vaccine procurement and production earlier, India came up with these hurdles but the Indian population still did not seem to be mobilizing swiftly towards vaccination centers. With the initial hesitancy, as soon as the vaccination started to speedup, India was hit severely by the second wave. The severe second wave has slowed down the vaccination pace and also it was one of the major contributing factor of vaccine hesitancy. To understand the nature of vaccine hesitancy and factors underlying it, we conducted an extensive online and offline surveys in Varanasi and adjoining regions using structured questions. Majority of respondents though were students (0.633), respondents from other occupations such as government officials (0.10) were also included in the study. We observed several intriguing opinions on our eleven questions. It is interesting to note that the majority of the 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 are still not interested in vaccination. People who have neither been vaccinated nor have ever been infected may become the medium for spreading the virus and creating new variants. This could also lead to a resistant variant of the vaccine in the future. We expect that this extensive survey may help the government to upgrade their vaccination policies for COVID-19 in North India.

Studies worldwide have shown that the available vaccines are highly effective against SARS-CoV-2. However, there are growing laboratory reports that the newer variants of concerns (VOCs e.g. Alpha, Beta, Delta etc) may evade vaccine induced defense. In addition to that, there are few ground reports on health workers having breakthrough infections. In order to understand VOC driven breakthrough infection we investigated 14 individuals who tested positive for SARS-CoV-2 after being administered a single or double dose of Covishield (ChAdOx1, Serum Institute of India) from the city of Varanasi, which is located in the Indian state of Uttar Pradesh. Genomic analysis revealed that 78.6% (11/14) of the patients were infected with the B.1.617.2 (Delta) variant. Notably, the frequency (37%) of this variant in the region was significantly lower (p

The ongoing COVID-19 pandemic has been a scientific, medical and social challenge. Since clinical course of this disease is largely unpredictable and can develop rapidly causing severe complications, it is important to identify laboratory biomarkers which may help to classify patient’s severity during initial stage. Previous studies have suggested C - reactive protein (inflammatory) and D-dimer (biochemical) as an effective biomarker. The differential severity in patients across the world and our limited understanding in the progression of the disease calls for a multi-country analysis for biomarkers. Therefore, we have analyzed these biomarkers among 228 Bangladeshi COVID-19 patients. We show significant association of COVID-19 severity with these two biomarkers. Thus, we suggest using these biomarkers for Bangladeshi COVID-19 patients for disease monitoring. Such validated preventive measures may decrease the case fatality ratio substantially.

The archipelago of Lakshadweep is considered as a stopover to the maritime route since ancient time. It is not very clear when the human first occupied these islands, however in the long history of the islands, the local legends suggest that Lakshadweep has been ruled by different kingdoms. To have a better understanding of peopling of Lakshadweep, we have analysed 557 individuals from eight major islands for mitochondrial DNA and 166 individuals for Y chromosome markers. We found a strong founder effect for both paternal and maternal lineages. Moreover, we report a close genetic link of Lakshadweep islanders with the Maldives, Sri Lanka and India. Most of the Lakshadweep islands share the haplogroups specific to South Asia and West Eurasia, except Minicoy Island that also shares haplogroups of East Eurasia. The paternal and maternal ancestries of the majority of island populations suggest their arrival from distinct sources. We found that the maternal ancestry was closer to South Indian populations, whereas the paternal ancestry was overwhelmed with the haplogroups, more common in the Maldives and North of India. In conclusion, our first genetic data suggest that the majority of human ancestry in Lakshadweep is largely derived from South Asia with minor influences from East and West Eurasia.

The COVID-19 pandemic resulted in multiple waves of infection worldwide. The large variations in case fatality rate among different geographical regions suggest that the human susceptibility against this virus varies substantially. Several studies from different parts of the world showed a significant association of ABO blood group and COVID-19 susceptibility. It was demonstrated that individuals with blood group O are at the lower risk of coronavirus infection. To establish the association of ABO blood group in SARS-CoV-2 susceptibility, we for the first time analysed SARS-CoV-2 neutralising antibodies among 509 individuals, collected from three major districts of Eastern Uttar Pradesh region of India. Interestingly, we found neutralising antibodies in a significantly higher percentage of people with blood group AB (0.36) followed by B (0.31), A (0.22) and lowest in people with blood group O (0.11). We further estimated that people with blood group AB are at comparatively higher risk of infection than other blood groups. Thus, among the asymptomatic SARS-CoV-2 recovered people blood group AB has highest, whilst individuals with blood group O has lowest risk of infection.

The COVID-19 pandemic has resulted several waves of infection in many countries worldwide. The large variations in case fatality ratio among different geographical regions suggests that the human susceptibility against this virus varies substantially. Several studies from different parts of the world showed a significant association of ABO blood group and COVID-19 susceptibility. It was shown that individuals with blood group O are at the lower risk of coronavirus infection. To establish the association of ABO blood group in SARS-CoV-2 susceptibility, we for the first time analysed SARS-CoV-2 neutralising antibodies as well as blood groups among 509 random individuals from three major districts of Eastern Uttar Pradesh region of India.. Interestingly, we found neutralising antibodies in significantly higher percentage of people with blood group AB (0.36) followed by B (0.31), A (0.22) and lowest in people with blood group O (0.11). This indicates that people with blood group AB are at comparatively higher risk of infection than other blood groups. Further, in line to previous reports we too observed that people with blood group O have significantly decreased risk of SARS-CoV-2 infection. Thus, among the asymptomatic SARS-CoV-2 infected individuals with blood group AB has highest, whilst blood group O has lowest risk of infection.

With the growing evidence on the variable human susceptibility against COVID-19, it is evident that some genetic loci modulate the severity of the infection. Recent studies have identified several loci associated with greater severity. More recently, a study has identified a 50kb segment introgressed from Neanderthal adding a risk for COVID-19, and this trait is present among 16% and 50% people of European and South Asian origin respectively. Contrary to this finding, our studies on ACE2 identified a haplotype present among 20% and 60% of European and South Asian populations respectively, which appears to be responsible for the low case fatality ratio among South Asian populations. This result was also consistent with the realtime infection rate and case fatality ratio among various states of India. We readdressed this issue using both of the contrasting datasets and compared them with the realtime infection rates and case fatality ratio in India. We found out that the polymorphism present in the 50kb introgressed segment (rs10490770) did not show any significant correlation with the realtime infection and case fatality ratio in India.

With the growing evidence on the variable human susceptibility against COVID-19, it is evident that some genetic loci modulate the severity of the infection. Recent studies have identified several loci associated with greater severity. More recently, a study has identified a 50 kb genomic segment introgressed from Neanderthal adding a risk for COVID-19, and this genomic segment is present among 16% and 50% people of European and South Asian descent, respectively. Our studies on ACE2 identified a haplotype present among 20% and 60% of European and South Asian populations, respectively, which appears to be responsible for the low case fatality rate among South Asian populations. This result was also consistent with the real-time infection rate and case fatality rate among various states of India. We readdressed this issue using both of the contrasting datasets and compared them with the real-time infection rates and case fatality rate in India. We found that the polymorphism present in the 50 kb introgressed genomic segment (rs10490770) did not show any significant correlation with the infection and case fatality rate in India.

With the growing evidence on the variable human susceptibility against COVID-19, it is clear that there are some genetic loci modulating the severity. Recent studies have identified several loci associated with the higher severity. More recently, a study has identified 50kb segment introgressed from Neanderthal adding risk for COVID-19, and is present among 16% and 50% people of European and South Asian origin respectively. Contrary to that, our studies on ACE2 identified a haplotype present among 20% and 60% of European and South Asian populations respectively, was probably responsible for the low case fatality ratio among South Asian populations. This result was also consistent with the realtime infection rate and case fatality ratio among various states of India. We readdressed this issue using both of the contrasting datasets and compared them with the realtime infection rates and case fatality ratio in India. We found out that that the polymorphism present in 50kb introgressed segment (rs10490770) did not show any significant correlation with the realtime infection and case fatality ratio in India.With the growing evidence on the variable human susceptibility against COVID-19, it is clear that there are some genetic loci modulating the severity. Recent studies have identified several loci associated with the higher severity. More recently, a study has identified 50kb segment introgressed from Neanderthal adding risk for COVID-19, and is present among 16% and 50% people of European and South Asian origin respectively. Contrary to that, our studies on ACE2 identified a haplotype present among 20% and 60% of European and South Asian populations respectively, was probably responsible for the low case fatality ratio among South Asian populations. This result was also consistent with the realtime infection rate and case fatality ratio among various states of India. We readdressed this issue using both of the contrasting datasets and compared them with the realtime infection rates and case fatality ratio in India. We found out that that the polymorphism present in 50kb introgressed segment (rs10490770) did not show any significant correlation with the realtime infection and case fatality ratio in India.

Studies on host-pathogen interaction have identified human ACE2 as a host cell receptor responsible for mediating infection by coronavirus (Covid-19). Subsequent studies have shown striking difference of allele frequency among Europeans and Asians for a polymorphism rs2285666, present in ACE2. It has been revealed that the alternate allele (TT-plus strand or AA-minus strand) of rs2285666 elevate the expression level of this gene upto 50%, hence may play a significant role in SARS-CoV-2 susceptibility. Therefore, we have first looked the phylogenetic structure of rs2285666 derived haplotypes in worldwide populations and compared the spatial frequency of this particular allele with respect to the Covid-19 infection as well as case-fatality rate in India. For the first time, we ascertained a significant positive correlation for alternate allele (T or A) of rs2285666, with the lower infection as well as case-fatality ratio among Indian populations. We trust that this information will be useful to understand the role of ACE2 in Covid-19 susceptibility.

Studies on host-pathogen interaction have identified human ACE2 as a host cell receptor responsible for mediating infection by coronavirus (COVID-19). Subsequent studies have shown striking difference of allele frequency among Europeans and Asians for a polymorphism rs2285666, present in ACE2. It has been revealed that the alternate allele (TT-plus strand or AA-minus strand) of rs2285666 elevate the expression level of this gene upto 50%, hence may play a significant role in SARS-CoV-2 susceptibility. Therefore, we have first looked the phylogenetic structure of rs2285666 derived haplotypes in worldwide populations and compared the spatial frequency of this particular allele with respect to the COVID-19 infection as well as case-fatality rate in India. For the first time, we ascertained a significant positive correlation for alternate allele (T or A) of rs2285666, with the lower infection as well as case-fatality rate among Indian populations. We trust that this information will be useful to understand the role of ACE2 in COVID-19 susceptibility.

SARS-CoV-2, the causative agent for COVID-19, an ongoing pandemic, engages the ACE2 receptor to enter the host cell through S protein priming by a serine protease, TMPRSS2. Variation in the TMPRSS2 gene may account for the disparity in disease susceptibility between populations. Therefore, in the present study, we have used next-generation sequencing (NGS) data of world populations from 393 individuals and analyzed the TMPRSS2 gene using a haplotype-based approach with a major focus on South Asia to study its phylogenetic structure and their haplotype sharing among various populations worldwide. Our analysis of phylogenetic relatedness showed a closer affinity of South Asians with the West Eurasian populations therefore, host disease susceptibility and severity particularly in the context of TMPRSS2 will be more akin to West Eurasian instead of East Eurasian. This is in contrast to our prior study on the ACE2 gene which shows South Asian haplotypes have a strong affinity towards West Eurasians. Thus ACE2 and TMPRSS2 have an antagonistic genetic relatedness among South Asians. Considering the significance of the TMPRSS2 gene in the SARS-CoV-2 pathogenicity, COVID-19 infection and intensity trends could be directly associated with increased expression therefore, we have also tested the SNPs frequencies of this gene among various Indian state populations with respect to the case fatality rate (CFR). Interestingly, we found a significant positive association between the rs2070788 SNP (G Allele) and the CFR among Indian populations. Further our cis eQTL analysis of rs2070788 shows that the GG genotype of the rs2070788 tends to have a significantly higher expression of TMPRSS2 gene in the lung compared to the AG and AA genotypes thus validating the previous observation and therefore it might play a vital part in determining differential disease vulnerability. We trust that this information will be useful in understanding the role of the TMPRSS2 variant in COVID-19 susceptibility and using it as a biomarker may help to predict populations at risk.

The South Asian populations have a mosaic of ancestries likely due to the interactions of long-term populations of the landmass and those of East and West Eurasia. Apart from prehistoric dispersals, there are some known population movements to India. In this study, we focussed on the migration of Jewish and Parsi populations on temporal and spatial scales. The existence of Jewish and Parsi communities in India are recorded since ancient times. However, due to the lack of high-resolution genetic data, their origin and affiliation with other Indian and non-Indian populations remains shrouded in legends. Earlier genetic studies on populations of Indian Jews have found evidence for a minor shared ancestry of Indian Jews with Middle Eastern (Jews) populations, whereas for Parsis, the Iranian link was proposed. Recently, in our high-resolution study, we were able to quantify the admixture dynamics of these groups, which has suggested a male-biased admixture. Here, we added the newly available ancient samples and revisited the interplay of genes and cultures. Thus, in this study we reconstructed a broad genetic profile of Indian Jews and Parsis to paint a fine-grained picture of these ethnic groups.