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Browsing by Author "Rudra Kumar Pandey"

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    PublicationErratum
    Correction to: Novel genetic association of the Furin gene polymorphism rs1981458 with COVID-19 severity among Indian populations (Scientific Reports, (2024), 14, 1, (7822), 10.1038/s41598-024-54607-7)
    (Nature Research, 2024) Rudra Kumar Pandey; Anshika Srivastava; Rahul Kumar Mishra; Prajjval Pratap Singh; Gyaneshwer Chaubey
    Correction to: Scientific Reportshttps://doi.org/10.1038/s41598-024-54607-7, published online 03 April 2024 The original version of this Article contained errors in the Material and Methods section and in the legend of Figure 3 (A, B, C). In the Material and Methods section, under the subheading ‘Insilco analysis’, “To analyse the TMPRSS2 expression in various human tissues, the GTEx portal database (http://www.gtexportal.org/home/) was used.” now reads: “To analyse the FURIN expression in various human tissues, the GTEx portal database (http://www.gtexportal.org/home/) was used.” In the legend of Figure 3, “(A) and (B) display the allele frequency distribution of rs2070788 across Indian populations in a frequency map and the corresponding COVID-19 Case Fatality Rate (CFR) as of August 30th, 2021.” now reads: “(A) and (B) display the allele frequency distribution of rs1981458 across Indian populations in a frequency map and the corresponding COVID-19 Case Fatality Rate (CFR) as of August 30th, 2021.” “The linear regression graph depicts the association between the rs1981458 allele frequency of the TMPRSS2 gene with COVID-19 CFR.” now reads: “The linear regression graph depicts the association between the rs1981458 allele frequency of the FURIN gene with COVID-19 CFR.” The original Article has been corrected. © The Author(s) 2024.
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    PublicationArticle
    Genetic Association of ACE2 rs2285666 Polymorphism With COVID-19 Spatial Distribution in India
    (Frontiers Media S.A., 2020) Anshika Srivastava; Audditiya Bandopadhyay; Debashurti Das; Rudra Kumar Pandey; Vanya Singh; Nargis Khanam; Nikhil Srivastava; Prajjval Pratap Singh; Pavan Kumar Dubey; Abhishek Pathak; Pranav Gupta; Niraj Rai; Gazi Nurun Nahar Sultana; Gyaneshwer Chaubey
    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. © Copyright © 2020 Srivastava, Bandopadhyay, Das, Pandey, Singh, Khanam, Srivastava, Singh, Dubey, Pathak, Gupta, Rai, Sultana and Chaubey.
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    PublicationArticle
    Genetic association of TMPRSS2 rs2070788 polymorphism with COVID-19 case fatality rate among Indian populations
    (Elsevier B.V., 2022) Rudra Kumar Pandey; Anshika Srivastava; Prajjval Pratap Singh; Gyaneshwer Chaubey
    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. © 2022
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    PublicationArticle
    Genetic Diversity and Spatiotemporal Distribution of SARS-CoV-2 Alpha Variant in India
    (Multidisciplinary Digital Publishing Institute (MDPI), 2023) Jahnavi Parasar; Rudra Kumar Pandey; Yashvant Patel; Prajjval Pratap Singh; Anshika Srivastava; Rahul Kumar Mishra; Bhupendra Kumar; Niraj Rai; Vijaya Nath Mishra; Pankaj Shrivastava; P. B. Kavi Kishor; Prashanth Suravajhala; Rakesh Tamang; Ajai Kumar Pathak; Gyaneshwer Chaubey
    After the spill to humans, in the evolutionary 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 the WHO, was discovered in the south-eastern United Kingdom (UK). Slowly, it expanded across India, with a considerable number of cases, particularly in North India. This study focuses on determining the prevalence and expansion of the Alpha variants in various parts of India mainly by using phylospatial analysis. The genetic diversity estimation has helped us to understand various evolutionary forces that have shaped the spatial distribution of this variant during its peak. Overall, our study paves the way to understanding the evolution and expansion of a virus variant, which may help to mitigate in the case of any future wave. © 2023 by the authors.
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    PublicationArticle
    Most frequent South Asian haplotypes of ACE2 share identity by descent with East Eurasian populations
    (Public Library of Science, 2020) Anshika Srivastava; Rudra Kumar Pandey; Prajjval Pratap Singh; Pramod Kumar; Avinash Arvind Rasalkar; Rakesh Tamang; George van Driem; Pankaj Shrivastava; Gyaneshwer Chaubey
    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. Copyright: © 2020 Srivastava et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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    PublicationArticle
    Multiple Domestication Centers of the Indian Pig Population
    (Oxford University Press, 2025) Shailesh Desai; Prajjval Pratap Singh; Rudra Kumar Pandey; Rahul Kumar Mishra; Akhilesh Kumar Chaubey; Ajit Kumar; Sachin Kumar Tiwary; Sandeep Kumar Gupta; A. Achilli; Nicola Rambaldi Migliore; G. Chaubey
    The domestication of animals is a major milestone in human history and has been studied in various fields. Pig domestication, in particular, has been widely studied, and it is believed that India is one of at least six domestication centers. However, there is a lack of systematic studies using high-resolution genetic markers, including complete mitogenomes, to investigate the domestication and genetic roots of pigs in India. In the present study, we investigated the origin and evolution of Indian pigs using mitochondrial genetic data to complement archaeological data sets. The phylogenetic status of Indian pig breeds was determined by analyzing all available mitochondrial data, incorporating a global data set of 239 mitogenomes. The Bayesian and maximum likelihood tree analyses unveiled at least eight haplogroups diverging from three main branches, two of which are geographically restricted to India. We propose that the North Indian domestic haplogroup might represent an independent in situ domestication event in North India, probably dating before ∼5,000 YBP. An additional North East Indian domestic haplogroup is nested within a widespread Asian clade that also includes Indian mitogenomes from the Andaman and Nicobar Islands that diverged more recently from distinct East and Southeast Asian roots. In conclusion, we propose that North Indian farmers could have been responsible for the independent domestication of local wild boars giving rise to the current domestic lineage identified in North India. At least one additional domestic lineage arrived in India more recently and remained mainly localized in the northeast. Domestic mitogenomes from the Indian islands show a notable connection with pig populations from Vietnam, and their arrival might be related to Austroasiatic-speaking human populations. Overall, this study provides valuable insights into the complex dynamics of pig domestication in India. © The Author(s) 2025. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.
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    PublicationArticle
    Novel genetic association of the Furin gene polymorphism rs1981458 with COVID-19 severity among Indian populations
    (Nature Research, 2024) Rudra Kumar Pandey; Anshika Srivastava; Rahul Kumar Mishra; Prajjval Pratap Singh; Gyaneshwer Chaubey
    SARS CoV-2, the causative agent for the ongoing COVID-19 pandemic, it enters the host cell by activating the ACE2 receptor with the help of two proteasesi.e., Furin and TMPRSS2. Therefore, variations in these genes may account for differential susceptibility and severity between populations. Previous studies have shown that the role of ACE2 and TMPRSS2 gene variants in understanding COVID-19 susceptibility among Indian populations. Nevertheless, a knowledge gap exists concerning the COVID-19 susceptibility of Furin gene variants among diverse South Asian ethnic groups. Investigating the role of Furin gene variants and their global phylogeographic structure is essential to comprehensively understanding COVID-19 susceptibility in these populations. We have used 450 samples from diverse Indian states and performed linear regression to analyse the Furin gene variant's with COVID-19 Case Fatality Rate (CFR) that could be epidemiologically associated with disease severity outcomes. Associated genetic variants were further evaluated for their expression and regulatory potential through various Insilco analyses. Additionally, we examined the Furin gene using next-generation sequencing (NGS) data from 393 diverse global samples, with a particular emphasis on South Asia, to investigate its Phylogeographic structure among diverse world populations. We found a significant positive association for the SNP rs1981458 with COVID-19 CFR (p < 0.05) among diverse Indian populations at different timelines of the first and second waves. Further, QTL and other regulatory analyses showed various significant associations for positive regulatory roles of rs1981458 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 phylogeographic architecture of the Furin gene demonstrated a closer genetic affinity of South Asia with West Eurasian populations. Therefore, it is worth proposing that for 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 genetic affinity of South Asian with East Eurasians and West Eurasians, respectively. Therefore, with the collective information from these three important genes (ACE2, TMPRSS2 and Furin) we modelled COVID-19 susceptibilityof South Asia in between these two major ancestries with an inclination towards West Eurasia. 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.This study also highlights that the genetic structure for COVID-19 susceptibilityof South Asia is distinct, however, inclined to the West Eurasian population. We believe this insight may 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 Author(s) 2024.
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