Journal of Genetic Engineering and Biotechnology (Dec 2021)

Genetic epidemiology of autoinflammatory disease variants in Indian population from 1029 whole genomes

  • Abhinav Jain,
  • Rahul C. Bhoyar,
  • Kavita Pandhare,
  • Anushree Mishra,
  • Disha Sharma,
  • Mohamed Imran,
  • Vigneshwar Senthivel,
  • Mohit Kumar Divakar,
  • Mercy Rophina,
  • Bani Jolly,
  • Arushi Batra,
  • Sumit Sharma,
  • Sanjay Siwach,
  • Arun G. Jadhao,
  • Nikhil V. Palande,
  • Ganga Nath Jha,
  • Nishat Ashrafi,
  • Prashant Kumar Mishra,
  • Vidhya A.K.,
  • Suman Jain,
  • Debasis Dash,
  • Nachimuthu Senthil Kumar,
  • Andrew Vanlallawma,
  • Ranjan Jyoti Sarma,
  • Lalchhandama Chhakchhuak,
  • Shantaraman Kalyanaraman,
  • Radha Mahadevan,
  • Sunitha Kandasamy,
  • Pabitha B. M,,
  • Raskin Erusan Rajagopal,
  • Ezhil Ramya J.,
  • Nirmala Devi P.,
  • Anjali Bajaj,
  • Vishu Gupta,
  • Samatha Mathew,
  • Sangam Goswami,
  • Mohit Mangla,
  • Savinitha Prakash,
  • Kandarp Joshi,
  • Meyakumla,
  • Sreedevi S.,
  • Devarshi Gajjar,
  • Ronibala Soraisham,
  • Rohit Yadav,
  • Yumnam Silla Devi,
  • Aayush Gupta,
  • Mitali Mukerji,
  • Sivaprakash Ramalingam,
  • Binukumar B. K.,
  • Vinod Scaria,
  • Sridhar Sivasubbu

DOI
https://doi.org/10.1186/s43141-021-00268-2
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 16

Abstract

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Abstract Background Autoinflammatory disorders are the group of inherited inflammatory disorders caused due to the genetic defect in the genes that regulates innate immune systems. These have been clinically characterized based on the duration and occurrence of unprovoked fever, skin rash, and patient’s ancestry. There are several autoinflammatory disorders that are found to be prevalent in a specific population and whose disease genetic epidemiology within the population has been well understood. However, India has a limited number of genetic studies reported for autoinflammatory disorders till date. The whole genome sequencing and analysis of 1029 Indian individuals performed under the IndiGen project persuaded us to perform the genetic epidemiology of the autoinflammatory disorders in India. Results We have systematically annotated the genetic variants of 56 genes implicated in autoinflammatory disorder. These genetic variants were reclassified into five categories (i.e., pathogenic, likely pathogenic, benign, likely benign, and variant of uncertain significance (VUS)) according to the American College of Medical Genetics and Association of Molecular pathology (ACMG-AMP) guidelines. Our analysis revealed 20 pathogenic and likely pathogenic variants with significant differences in the allele frequency compared with the global population. We also found six causal founder variants in the IndiGen dataset belonging to different ancestry. We have performed haplotype prediction analysis for founder mutations haplotype that reveals the admixture of the South Asian population with other populations. The cumulative carrier frequency of the autoinflammatory disorder in India was found to be 3.5% which is much higher than reported. Conclusion With such frequency in the Indian population, there is a great need for awareness among clinicians as well as the general public regarding the autoinflammatory disorder. To the best of our knowledge, this is the first and most comprehensive population scale genetic epidemiological study being reported from India.

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