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.
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Data availability
The data sets supporting the findings of this article are included within the article and as Supplementary Data. The variant file for the final SV callset is made available for download on the IndiGenomes database website. https://clingen.igib.res.in/indigen/.
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Acknowledgements
Authors acknowledge the funding support from the Council of Scientific and Industrial Research (CSIR) India (Grant No. MLP1809, MLP1801, MLP2001). Authors acknowledge all the volunteers who participated in this study. MKD, AJ, AB, and BJ acknowledge the CSIR fellowship; MI acknowledges the ICMR fellowship; DS acknowledges Intel research fellowship; VG acknowledges the UGC fellowship. The funding body has no role in the design of the study and in writing the manuscript.
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SSB and V Scaria conceived the idea; MKD, AJ, RCB, VS, BJ, MI, DS, AB, and VG performed research; and MKD, SSB, and VS wrote the manuscript. All authors read and approved the final manuscript.
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This study was approved by the Institutional Human Ethics Committee (IHEC) of the CSIR-Institute of Genomics and Integrative Biology. The participants were explained about the informed consent process as per the approved IHEC guidelines.
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10038_2023_1131_MOESM1_ESM.docx
Data on benchmarking for variant detection tool, supplementary method for variant filtering and disease status of rare deletions affected genes in DDD and OMIM database
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Divakar, M.K., Jain, A., Bhoyar, R.C. et al. Whole-genome sequencing of 1029 Indian individuals reveals unique and rare structural variants. J Hum Genet 68, 409–417 (2023). https://doi.org/10.1038/s10038-023-01131-7
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DOI: https://doi.org/10.1038/s10038-023-01131-7
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