The Genomic landscape of short tandem repeats across multiple ancestries.
Short Tandem Repeats (STRs) have been found to play a role in a myriad of complex traits and genetic diseases. We examined the variability in the lengths of over 850,000 STR loci in 996 children with suspected genetic disorders and 1,178 parents across six separate ancestral groups: Africans, Europe...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0279430 |
| _version_ | 1797866830739537920 |
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| author | Prashanth Vijayaraghavan Sergey Batalov Yan Ding Erica Sanford Stephen F Kingsmore David Dimmock Charlotte Hobbs Matthew Bainbridge |
| author_facet | Prashanth Vijayaraghavan Sergey Batalov Yan Ding Erica Sanford Stephen F Kingsmore David Dimmock Charlotte Hobbs Matthew Bainbridge |
| author_sort | Prashanth Vijayaraghavan |
| collection | DOAJ |
| description | Short Tandem Repeats (STRs) have been found to play a role in a myriad of complex traits and genetic diseases. We examined the variability in the lengths of over 850,000 STR loci in 996 children with suspected genetic disorders and 1,178 parents across six separate ancestral groups: Africans, Europeans, East Asians, Admixed Americans, Non-admixed Americans, and Pacific Islanders. For each STR locus we compared allele length between and within each ancestry group. In relation to Europeans, admixed Americans had the most similar STR lengths with only 623 positions either significantly expanded or contracted, while the divergence was highest in Africans, with 4,933 chromosomal positions contracted or expanded. We also examined probands to identify STR expansions at known pathogenic loci. The genes TCF4, AR, and DMPK showed significant expansions with lengths 250% greater than their various average allele lengths in 49, 162, and 11 individuals respectively. All 49 individuals containing an expansion in TCF4 and six individuals containing an expansion in DMPK presented with allele lengths longer than the known pathogenic length for these genes. Next, we identified individuals with significant expansions in highly conserved loci across all ancestries. Eighty loci in conserved regions met criteria for divergence. Two of these individuals were found to have exonic STR expansions: one in ZBTB4 and the other in SLC9A7, which is associated with X-linked mental retardation. Finally, we used parent-child trios to detect and analyze de novo mutations. In total, we observed 3,219 de novo expansions, where proband allele lengths are greater than twice the longest parental allele length. This work helps lay the foundation for understanding STR lengths genome-wide across ancestries and may help identify new disease genes and novel mechanisms of pathogenicity in known disease genes. |
| first_indexed | 2024-04-09T23:30:34Z |
| format | Article |
| id | doaj.art-40f4b5dc4d714604b4455eb64f5ce690 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-09T23:30:34Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-40f4b5dc4d714604b4455eb64f5ce6902023-03-21T05:31:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01181e027943010.1371/journal.pone.0279430The Genomic landscape of short tandem repeats across multiple ancestries.Prashanth VijayaraghavanSergey BatalovYan DingErica SanfordStephen F KingsmoreDavid DimmockCharlotte HobbsMatthew BainbridgeShort Tandem Repeats (STRs) have been found to play a role in a myriad of complex traits and genetic diseases. We examined the variability in the lengths of over 850,000 STR loci in 996 children with suspected genetic disorders and 1,178 parents across six separate ancestral groups: Africans, Europeans, East Asians, Admixed Americans, Non-admixed Americans, and Pacific Islanders. For each STR locus we compared allele length between and within each ancestry group. In relation to Europeans, admixed Americans had the most similar STR lengths with only 623 positions either significantly expanded or contracted, while the divergence was highest in Africans, with 4,933 chromosomal positions contracted or expanded. We also examined probands to identify STR expansions at known pathogenic loci. The genes TCF4, AR, and DMPK showed significant expansions with lengths 250% greater than their various average allele lengths in 49, 162, and 11 individuals respectively. All 49 individuals containing an expansion in TCF4 and six individuals containing an expansion in DMPK presented with allele lengths longer than the known pathogenic length for these genes. Next, we identified individuals with significant expansions in highly conserved loci across all ancestries. Eighty loci in conserved regions met criteria for divergence. Two of these individuals were found to have exonic STR expansions: one in ZBTB4 and the other in SLC9A7, which is associated with X-linked mental retardation. Finally, we used parent-child trios to detect and analyze de novo mutations. In total, we observed 3,219 de novo expansions, where proband allele lengths are greater than twice the longest parental allele length. This work helps lay the foundation for understanding STR lengths genome-wide across ancestries and may help identify new disease genes and novel mechanisms of pathogenicity in known disease genes.https://doi.org/10.1371/journal.pone.0279430 |
| spellingShingle | Prashanth Vijayaraghavan Sergey Batalov Yan Ding Erica Sanford Stephen F Kingsmore David Dimmock Charlotte Hobbs Matthew Bainbridge The Genomic landscape of short tandem repeats across multiple ancestries. PLoS ONE |
| title | The Genomic landscape of short tandem repeats across multiple ancestries. |
| title_full | The Genomic landscape of short tandem repeats across multiple ancestries. |
| title_fullStr | The Genomic landscape of short tandem repeats across multiple ancestries. |
| title_full_unstemmed | The Genomic landscape of short tandem repeats across multiple ancestries. |
| title_short | The Genomic landscape of short tandem repeats across multiple ancestries. |
| title_sort | genomic landscape of short tandem repeats across multiple ancestries |
| url | https://doi.org/10.1371/journal.pone.0279430 |
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