Whole-genome sequencing of 1029 Indian individuals reveals unique and rare structural variants

Abstract

Structural variants contribute to genetic variability in human genomes and they can be presented in population-specific patterns. We aimed to understand the landscape of structural variants in the genomes of healthy Indian individuals and explore their potential implications in genetic disease conditions. For the identification of structural variants, a whole genome sequencing dataset of 1029 self-declared healthy Indian individuals from the IndiGen project was analysed. Further, these variants were evaluated for potential pathogenicity and their associations with genetic diseases. We also compared our identified variations with the existing global datasets. We generated a compendium of total 38,560 high-confident structural variants, comprising 28,393 deletions, 5030 duplications, 5038 insertions, and 99 inversions. Particularly, we identified around 55% of all these variants were found to be unique to the studied population. Further analysis revealed 134 deletions with predicted pathogenic/likely pathogenic effects and their affected genes were majorly enriched for neurological disease conditions, such as intellectual disability and neurodegenerative diseases. The IndiGenomes dataset helped us to understand the unique spectrum of structural variants in the Indian population. More than half of identified variants were not present in the publicly available global dataset on structural variants. Clinically important deletions identified in IndiGenomes might aid in improving the diagnosis of unsolved genetic diseases, particularly in neurological conditions. Along with basal allele frequency data and clinically important deletions, IndiGenomes data might serve as a baseline resource for future studies on genomic structural variant analysis in the Indian population.