Landscape of genomic structural variations in Indian population-based cohorts: Deeper insights into their prevalence and clinical relevance

Subramanian, K and Chopra, M and Kahali, B (2024) Landscape of genomic structural variations in Indian population-based cohorts: Deeper insights into their prevalence and clinical relevance. In: Human Genetics and Genomics Advances, 5 (3).

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Abstract

Structural variations (SV) are large (>50 base pairs) genomic rearrangements comprising deletions, duplications, insertions, inversions, and translocations. Studying SVs is important because they play active and critical roles in regulating gene expression, determining disease predispositions, and identifying population-specific differences among individuals of diverse ancestries. However, SV discoveries in the Indian population using whole-genome sequencing (WGS) have been limited. In this study, using short-read WGS having an average 42X depth of coverage, we identify and characterize 36,210 SVs from 529 individuals enrolled in population-based cohorts in India. These SVs include 24,574 deletions, 2,913 duplications, 8,710 insertions, and 13 inversions; 1.26 (456 out of 36,210) of the identified SVs can potentially impact the coding regions of genes. Furthermore, 56 of these SVs are highly intolerant to loss-of-function changes to the mapped genes, and five SVs impacting ADAMTS17, CCDC40, and RHCE are common in our study individuals. Seven rare SVs significantly impact dosage sensitivity of genes known to be associated with various clinical phenotypes. Most of the SVs in our study are rare and heterozygous. This fine-scale SV discovery in the underrepresented Indian population provides valuable insights that extend beyond Eurocentric human genetic studies. © 2024 The Authors

Item Type:	Journal Article
Publication:	Human Genetics and Genomics Advances
Publisher:	Elsevier Inc.
Additional Information:	The copyright for this article belongs to authors.
Keywords:	adult; allele; Article; clinical article; clinical significance; deletion mutant; female; gene duplication; gene frequency; gene insertion; gene mutation; gene structure; gene translocation; genetic association; genetic variability; genetic variation; genotype; genotyping; haplotype; heterozygosity; human; leukocyte count; male; middle aged; mutational analysis; neuroimaging; real time polymerase chain reaction; single nucleotide polymorphism; whole exome sequencing; whole genome sequencing
Department/Centre:	Autonomous Societies / Centres > Centre for Brain Research
Date Deposited:	08 Jul 2024 06:37
Last Modified:	08 Jul 2024 06:37
URI:	http://eprints.iisc.ac.in/id/eprint/84737

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