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© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Details

Title
Genetic epidemiology of autoinflammatory disease variants in Indian population from 1029 whole genomes
Author
Jain, Abhinav 1 ; Bhoyar, Rahul C. 2 ; Pandhare, Kavita 2 ; Mishra, Anushree 2 ; Sharma, Disha 2 ; Imran, Mohamed 1 ; Senthivel, Vigneshwar 1 ; Divakar, Mohit Kumar 1 ; Rophina, Mercy 1 ; Jolly, Bani 1 ; Batra, Arushi 1 ; Sharma, Sumit 2 ; Siwach, Sanjay 2 ; Jadhao, Arun G. 3 ; Palande, Nikhil V. 4 ; Jha, Ganga Nath 5 ; Ashrafi, Nishat 5 ; Mishra, Prashant Kumar 6 ; A.K., Vidhya 7 ; Jain, Suman 8 ; Dash, Debasis 1 ; Kumar, Nachimuthu Senthil 9 ; Vanlallawma, Andrew 9 ; Sarma, Ranjan Jyoti 9 ; Chhakchhuak, Lalchhandama 10 ; Kalyanaraman, Shantaraman 11 ; Mahadevan, Radha 11 ; Kandasamy, Sunitha 11 ; B. M,, Pabitha 11 ; Rajagopal, Raskin Erusan 11 ; Ramya J., Ezhil 11 ; Devi P., Nirmala 11 ; Bajaj, Anjali 1 ; Gupta, Vishu 1 ; Mathew, Samatha 1 ; Goswami, Sangam 1 ; Mangla, Mohit 1 ; Prakash, Savinitha 2 ; Joshi, Kandarp 2 ; Meyakumla 2 ; S., Sreedevi 12 ; Gajjar, Devarshi 13 ; Soraisham, Ronibala 14 ; Yadav, Rohit 1 ; Devi, Yumnam Silla 15 ; Gupta, Aayush 16 ; Mukerji, Mitali 1 ; Ramalingam, Sivaprakash 1 ; B. K., Binukumar 1 ; Scaria, Vinod 1   VIAFID ORCID Logo  ; Sivasubbu, Sridhar 1 

 CSIR-Institute of Genomics and Integrative Biology, New Delhi, India (GRID:grid.417639.e); Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India (GRID:grid.469887.c) (ISNI:0000 0004 7744 2771) 
 CSIR-Institute of Genomics and Integrative Biology, New Delhi, India (GRID:grid.417639.e) 
 RTM Nagpur University, Department of Zoology, Nagpur, India (GRID:grid.411997.3) (ISNI:0000 0001 1177 8457) 
 Shri Mathuradas Mohota College of Science, Department of Zoology, Nagpur, India (GRID:grid.411997.3) 
 Vinoba Bhave University, Department of Anthropology, Hazaribag, India (GRID:grid.444436.5) (ISNI:0000 0004 1799 5833) 
 Vinoba Bhave University, Department of Biotechnology, Hazaribag, India (GRID:grid.444436.5) (ISNI:0000 0004 1799 5833) 
 Dr. Kongu Science and Art College, Department of Biochemistry, Erode, India (GRID:grid.444436.5) 
 Thalassemia and Sickle Cell Society, Hyderabad, India (GRID:grid.444436.5) 
 Mizoram University, Department of Biotechnology, Aizawl, India (GRID:grid.411813.e) (ISNI:0000 0000 9217 3865) 
10  Civil Hospital Aizawl, Department of Pathology, Mizoram, India (GRID:grid.414546.6) (ISNI:0000 0004 1759 4765) 
11  TVMC, Tirunelveli Medical College, Tirunelveli, India (GRID:grid.469173.e) (ISNI:0000 0004 1801 7222) 
12  St.Pious X Degree & PG College for Women, Department of Microbiology, Hyderabad, India (GRID:grid.417639.e) 
13  The Maharaja Sayajirao University of Baroda, Department of Microbiology, Vadodara, India (GRID:grid.411494.d) (ISNI:0000 0001 2154 7601) 
14  Venereology and Leprology, Regional Institute of Medical Sciences, Department of Dermatology, Imphal, India (GRID:grid.415790.e) (ISNI:0000 0004 1767 1548) 
15  CSIR- North East Institute of Science and Technology, Jorhat, India (GRID:grid.462670.1) (ISNI:0000 0004 1802 8319) 
16  Dr. D.Y. Patil Medical College, Department of Dermatology, Pune, India (GRID:grid.464654.1) (ISNI:0000 0004 1764 8110) 
Pages
183
Publication year
2021
Publication date
Dec 2021
Publisher
Springer Nature B.V.
ISSN
1687157X
e-ISSN
20905920
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2812343625
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.