Landscape of genomic structural variations in Indian population-based cohorts: Deeper insights into their prevalence and clinical relevance
Summary: 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 predisposi...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-07-01
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| Series: | HGG Advances |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666247724000241 |
| _version_ | 1827288799814615040 |
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| author | Krithika Subramanian Mehak Chopra Bratati Kahali |
| author_facet | Krithika Subramanian Mehak Chopra Bratati Kahali |
| author_sort | Krithika Subramanian |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-24T11:37:49Z |
| format | Article |
| id | doaj.art-e32030aa3f5f44df9a459236b858227e |
| institution | Directory Open Access Journal |
| issn | 2666-2477 |
| language | English |
| last_indexed | 2024-04-24T11:37:49Z |
| publishDate | 2024-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | HGG Advances |
| spelling | doaj.art-e32030aa3f5f44df9a459236b858227e2024-04-10T04:29:29ZengElsevierHGG Advances2666-24772024-07-0153100285Landscape of genomic structural variations in Indian population-based cohorts: Deeper insights into their prevalence and clinical relevanceKrithika Subramanian0Mehak Chopra1Bratati Kahali2Centre for Brain Research, Indian Institute of Science, Bangalore 560012, India; Manipal Academy of Higher Education, Manipal, Karnataka 576104, IndiaCentre for Brain Research, Indian Institute of Science, Bangalore 560012, IndiaCentre for Brain Research, Indian Institute of Science, Bangalore 560012, India; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2666247724000241Structural variationwhole-genome sequencinggenotypingrarecommonconstraint on missense |
| spellingShingle | Krithika Subramanian Mehak Chopra Bratati Kahali Landscape of genomic structural variations in Indian population-based cohorts: Deeper insights into their prevalence and clinical relevance HGG Advances Structural variation whole-genome sequencing genotyping rare common constraint on missense |
| title | Landscape of genomic structural variations in Indian population-based cohorts: Deeper insights into their prevalence and clinical relevance |
| title_full | Landscape of genomic structural variations in Indian population-based cohorts: Deeper insights into their prevalence and clinical relevance |
| title_fullStr | Landscape of genomic structural variations in Indian population-based cohorts: Deeper insights into their prevalence and clinical relevance |
| title_full_unstemmed | Landscape of genomic structural variations in Indian population-based cohorts: Deeper insights into their prevalence and clinical relevance |
| title_short | Landscape of genomic structural variations in Indian population-based cohorts: Deeper insights into their prevalence and clinical relevance |
| title_sort | landscape of genomic structural variations in indian population based cohorts deeper insights into their prevalence and clinical relevance |
| topic | Structural variation whole-genome sequencing genotyping rare common constraint on missense |
| url | http://www.sciencedirect.com/science/article/pii/S2666247724000241 |
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