Spectrum of rare and common mitochondrial DNA variations from 1029 whole genomes of self-declared healthy individuals from India.

Autor: Gupta V; CSIR Institute of Genomics and Integrative Biology, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Jolly B; CSIR Institute of Genomics and Integrative Biology, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Bhoyar RC; CSIR Institute of Genomics and Integrative Biology, New Delhi 110025, India., Divakar MK; CSIR Institute of Genomics and Integrative Biology, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Jain A; CSIR Institute of Genomics and Integrative Biology, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Mishra A; CSIR Institute of Genomics and Integrative Biology, New Delhi 110025, India., Senthivel V; CSIR Institute of Genomics and Integrative Biology, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Imran M; CSIR Institute of Genomics and Integrative Biology, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India., Scaria V; CSIR Institute of Genomics and Integrative Biology, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: vinods@igib.in., Sivasubbu S; CSIR Institute of Genomics and Integrative Biology, New Delhi 110025, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: sridhar@igib.in.
Jazyk: angličtina
Zdroj: Computational biology and chemistry [Comput Biol Chem] 2024 Oct; Vol. 112, pp. 108118. Date of Electronic Publication: 2024 Jun 10.
DOI: 10.1016/j.compbiolchem.2024.108118
Abstrakt: Mitochondrial disorders are a class of heterogeneous disorders caused by genetic variations in the mitochondrial genome (mtDNA) as well as the nuclear genome. The spectrum of mtDNA variants remains unexplored in the Indian population. In the present study, we have cataloged 2689 high confidence single nucleotide variants, small insertions and deletions in mtDNA in 1029 healthy Indian individuals. We found a major proportion (76.5 %) of the variants being rare (AF<=0.005) in the studied population. Intriguingly, we found two 'confirmed' pathogenic variants (m.1555 A>G and m.14484 T>C) with a frequency of ∼1 in 250 individuals in our dataset. The high carrier frequency underscores the need for screening of the mtDNA pathogenic mutations in newborns in India. Interestingly, our analysis also revealed 202 variants in our dataset which have been 'reported' in disease cases as per the MITOMAP database. Additionally, we found the frequency of haplogroup M (52.2 %) to be the highest among all the 18 top-level haplogroups found in our dataset. In comparison to the global population datasets, 20 unique mtDNA variants are found in the Indian population. We hope the whole genome sequencing based compendium of mtDNA variants along with their allele frequencies and heteroplasmy levels in the Indian population will drive additional genome scale studies for mtDNA. Furthermore, the identification of clinically relevant variants in our dataset will aid in better clinical interpretation of the variants in mitochondrial disorders.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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