The central region of India is incredibly rich in tribal heritage. It is the most frequent Indian... more 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 cuttingedge 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 identi ed 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).
With the growing evidence on the variable human susceptibility against COVID-19, it is evident th... more 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 identi ed several loci associated with greater severity. More recently, a study has identi ed 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 nding, our studies on ACE2 identi ed 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 signi cant correlation with the realtime infection and case fatality ratio in India.
Background SARS CoV-2, the causative agent for the ongoing COVID-19 pandemic, enters the host cel... more 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 signi cant positive association for the rs1981458 with COVID-19 CFR among diverse Indian populations. Further QTL and other regulatory analyses showed various signi cant 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 in ammation mechanism. The phylogenetic architecture of the Furin gene demonstrated a closer genetic a nity 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 a nity 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 Page 3/21 In conclusion, this study, for the rst 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.
With the rollout of the world's largest vaccine drive for SARS-CoV-by the Government of India on ... more With the rollout of the world's largest vaccine drive for SARS-CoV-by the Government of India on January , India had targeted to vaccinate its entire population by the end of. 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 o ine surveys in Varanasi and adjoining regions using structured questions. Most respondents were students (.). However, respondents from other occupations, such as government o cials (.), have also participated in the study. Interestingly, most people (.) relied on fake news and did not take COVID-seriously. Most importantly, we noticed that a substantial proportion of respondents (relative frequency. ; mean age. years) reported that they were still not interested in vaccination. We observed a significant association between vaccine hesitancy and socioeconomic status (χ =. , p < .). However, we failed to detect any association between vaccine hesitancy and gender (χ =. , p > .). 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-in North India.
medRxiv (Cold Spring Harbor Laboratory), Sep 22, 2021
Studies worldwide have shown that the available vaccines are highly effective against SARS-CoV-2.... more 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<0.01), suggesting that the vaccinated people were asymmetrically infected with the Delta variant. Most of the patients tested displayed mild symptoms, indicating that even a single dose of the vaccine can help in reducing the severity of the disease. However, more comprehensive epidemiological studies are required to understand the effectiveness of vaccines against the newer VOCs.
SARS-CoV2, the causative agent for COVID-19, an ongoing pandemic, engages the ACE2 receptor to en... more SARS-CoV2, 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 as it's not known. 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.
Studies on host-pathogen interaction have identified human ACE2 as a host cell receptor responsib... more 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.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
The ongoing COVID-19 pandemic has been a scienti c, medical and social challenge. Since clinical ... more The ongoing COVID-19 pandemic has been a scienti c, 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 (in ammatory) 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 signi cant 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.
Both classical and recent genetic studies have unanimously concluded that the genetic landscape o... more 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. The Indian subcontinent is renowned for the cultural, linguistic and genetic diversity of its inhabitants 1,2. This diversity has mainly arisen, in part, through long term human settlement, social customs and genetic drift 3-5. Broadly, Indian populations can be categorised as the castes, tribes, linguistic and religious communities. Presently, India counts hundreds of tribal groups, belonging to four major language families; Austroasiatic, Dravidian, Indo-European and Tibeto-Burman 6,7. Kol is one of them, with their major concentration in Central India (Fig. 1A). Kol is another name for Ho, whose language is a member of the Kherwarian cluster within the Northern Branch of the Munda subgroup of Austroasiatic language family 7-9. In fact, the language family came to be known as 'Mon-Khmer-Kolarian' when Francis Mason first identified that Kol and the other Munda languages were related to the Mon language of eastern Burma and Thailand in 1854. He suggested that these Munda or 'Kolarian' languages of India and the 'Mon-Annam' languages of Southeast Asia, collectively belonged to one and the same language family 10. The language family was given its current name ' Austroasiatic' in 1904 by Wilhelm Schmidt 11-15 .
The South Asian populations have a mosaic of ancestries likely due to the interactions of long-te... more 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.
The phylogenetic analysis of Y chromosomal haplogroup O2a-M95 was crucial to determine the nested... more 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.
With the growing evidence on the variable human susceptibility against COVID-19, it is evident th... more 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.
The ongoing COVID-19 pandemic has been a scientific, medical and social challenge. Since clinical... more 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 observed significant association of COVID-19 severity with these two biomarkers. Thus, we suggest to use these biomarkers for Bangladeshi COVID-19 patients for better disease monitoring. Such validated preventive measures may decrease the case fatality ratio substantially.
With the growing evidence on the variable human susceptibility against COVID-19, it is clear that... more 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.
The phylogenetic analysis of Y chromosomal haplogroup O2a-M95 was crucial to determine the nested... more 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 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 1,437 male
medRxiv (Cold Spring Harbor Laboratory), Oct 25, 2021
doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
The central region of India is incredibly rich in tribal heritage. It is the most frequent Indian... more 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 cuttingedge 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 identi ed 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).
With the growing evidence on the variable human susceptibility against COVID-19, it is evident th... more 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 identi ed several loci associated with greater severity. More recently, a study has identi ed 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 nding, our studies on ACE2 identi ed 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 signi cant correlation with the realtime infection and case fatality ratio in India.
Background SARS CoV-2, the causative agent for the ongoing COVID-19 pandemic, enters the host cel... more 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 signi cant positive association for the rs1981458 with COVID-19 CFR among diverse Indian populations. Further QTL and other regulatory analyses showed various signi cant 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 in ammation mechanism. The phylogenetic architecture of the Furin gene demonstrated a closer genetic a nity 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 a nity 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 Page 3/21 In conclusion, this study, for the rst 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.
With the rollout of the world's largest vaccine drive for SARS-CoV-by the Government of India on ... more With the rollout of the world's largest vaccine drive for SARS-CoV-by the Government of India on January , India had targeted to vaccinate its entire population by the end of. 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 o ine surveys in Varanasi and adjoining regions using structured questions. Most respondents were students (.). However, respondents from other occupations, such as government o cials (.), have also participated in the study. Interestingly, most people (.) relied on fake news and did not take COVID-seriously. Most importantly, we noticed that a substantial proportion of respondents (relative frequency. ; mean age. years) reported that they were still not interested in vaccination. We observed a significant association between vaccine hesitancy and socioeconomic status (χ =. , p < .). However, we failed to detect any association between vaccine hesitancy and gender (χ =. , p > .). 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-in North India.
medRxiv (Cold Spring Harbor Laboratory), Sep 22, 2021
Studies worldwide have shown that the available vaccines are highly effective against SARS-CoV-2.... more 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<0.01), suggesting that the vaccinated people were asymmetrically infected with the Delta variant. Most of the patients tested displayed mild symptoms, indicating that even a single dose of the vaccine can help in reducing the severity of the disease. However, more comprehensive epidemiological studies are required to understand the effectiveness of vaccines against the newer VOCs.
SARS-CoV2, the causative agent for COVID-19, an ongoing pandemic, engages the ACE2 receptor to en... more SARS-CoV2, 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 as it's not known. 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.
Studies on host-pathogen interaction have identified human ACE2 as a host cell receptor responsib... more 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.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
The ongoing COVID-19 pandemic has been a scienti c, medical and social challenge. Since clinical ... more The ongoing COVID-19 pandemic has been a scienti c, 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 (in ammatory) 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 signi cant 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.
Both classical and recent genetic studies have unanimously concluded that the genetic landscape o... more 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. The Indian subcontinent is renowned for the cultural, linguistic and genetic diversity of its inhabitants 1,2. This diversity has mainly arisen, in part, through long term human settlement, social customs and genetic drift 3-5. Broadly, Indian populations can be categorised as the castes, tribes, linguistic and religious communities. Presently, India counts hundreds of tribal groups, belonging to four major language families; Austroasiatic, Dravidian, Indo-European and Tibeto-Burman 6,7. Kol is one of them, with their major concentration in Central India (Fig. 1A). Kol is another name for Ho, whose language is a member of the Kherwarian cluster within the Northern Branch of the Munda subgroup of Austroasiatic language family 7-9. In fact, the language family came to be known as 'Mon-Khmer-Kolarian' when Francis Mason first identified that Kol and the other Munda languages were related to the Mon language of eastern Burma and Thailand in 1854. He suggested that these Munda or 'Kolarian' languages of India and the 'Mon-Annam' languages of Southeast Asia, collectively belonged to one and the same language family 10. The language family was given its current name ' Austroasiatic' in 1904 by Wilhelm Schmidt 11-15 .
The South Asian populations have a mosaic of ancestries likely due to the interactions of long-te... more 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.
The phylogenetic analysis of Y chromosomal haplogroup O2a-M95 was crucial to determine the nested... more 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.
With the growing evidence on the variable human susceptibility against COVID-19, it is evident th... more 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.
The ongoing COVID-19 pandemic has been a scientific, medical and social challenge. Since clinical... more 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 observed significant association of COVID-19 severity with these two biomarkers. Thus, we suggest to use these biomarkers for Bangladeshi COVID-19 patients for better disease monitoring. Such validated preventive measures may decrease the case fatality ratio substantially.
With the growing evidence on the variable human susceptibility against COVID-19, it is clear that... more 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.
The phylogenetic analysis of Y chromosomal haplogroup O2a-M95 was crucial to determine the nested... more 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 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 1,437 male
medRxiv (Cold Spring Harbor Laboratory), Oct 25, 2021
doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by pee... more doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
Uploads
Papers by PRAJJVAL SINGH