The impact of the Turkish population variome on the genomic architecture of rare disease traits

Purpose: The variome of the Turkish (TK) population, a population with a considerable history of admixture and consanguinity, has not been deeply investigated for insights on the genomic architecture of disease. Methods: We generated and analyzed a database of variants derived from exome sequencing...

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Autores: Coban-Akdemir, Zeynep, Song, Xiaofei, Ceballos, Francisco C, Pehlivan, Davut, Karaca, Ender, Bayram, Yavuz, Mitani, Tadahiro, Gambin, Tomasz, Bozkurt-Yozgatli, Tugce, Jhangiani, Shalini N, Muzny, Donna M, Lewis, Richard A, Liu, Pengfei, Boerwinkle, Eric, Hamosh, Ada, Gibbs, Richard A, Sutton, V Reid, Sobreira, Nara, Carvalho, Claudia M B, Shaw, Chad A, Posey, Jennifer E, Valle, David, Lupski, James R
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/26595
Acceso en línea:https://hdl.handle.net/20.500.12105/26595
Access Level:acceso abierto
Palabra clave:Admixture
Consanguinity
Genomic architecture of rare disease traits
Runs of homozygosity
Turkish population
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spelling The impact of the Turkish population variome on the genomic architecture of rare disease traitsCoban-Akdemir, ZeynepSong, XiaofeiCeballos, Francisco CPehlivan, DavutKaraca, EnderBayram, YavuzMitani, TadahiroGambin, TomaszBozkurt-Yozgatli, TugceJhangiani, Shalini NMuzny, Donna MLewis, Richard ALiu, PengfeiBoerwinkle, EricHamosh, AdaGibbs, Richard ASutton, V ReidSobreira, NaraCarvalho, Claudia M BShaw, Chad APosey, Jennifer EValle, DavidLupski, James RAdmixtureConsanguinityGenomic architecture of rare disease traitsRuns of homozygosityTurkish populationPurpose: The variome of the Turkish (TK) population, a population with a considerable history of admixture and consanguinity, has not been deeply investigated for insights on the genomic architecture of disease. Methods: We generated and analyzed a database of variants derived from exome sequencing data of 773 TK unrelated, clinically affected individuals with various suspected Mendelian disease traits and 643 unaffected relatives. Results: Using uniform manifold approximation and projection, we showed that the TK genomes are more similar to those of Europeans and consist of 2 main subpopulations: clusters 1 and 2 (N = 235 and 1181, respectively), which differ in admixture proportion and variome (https://turkishvariomedb.shinyapps.io/tvdb/). Furthermore, the higher inbreeding coefficient values observed in the TK affected compared with unaffected individuals correlated with a larger median span of long-sized (>2.64 Mb) runs of homozygosity (ROH) regions (P value = 2.09e-18). We show that long-sized ROHs are more likely to be formed on recently configured haplotypes enriched for rare homozygous deleterious variants in the TK affected compared with TK unaffected individuals (P value = 3.35e-11). Analysis of genotype-phenotype correlations reveals that genes with rare homozygous deleterious variants in long-sized ROHs provide the most comprehensive set of molecular diagnoses for the observed disease traits with a systematic quantitative analysis of Human Phenotype Ontology terms. Conclusion: Our findings support the notion that novel rare variants on newly configured haplotypes arising within the recent past generations of a family or clan contribute significantly to recessive disease traits in the TK population.ElsevierNIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos)NIH - National Institute of Neurological Disorders and Stroke (NINDS) (Estados Unidos)NIH - National Human Genome Research Institute (NHGRI) (Estados Unidos)Baylor Scott & White Research Institute (Estados Unidos)20252025-03-3120242024-01-0120242024-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/20.500.12105/26595reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/265952026-06-12T12:43:37Z
dc.title.none.fl_str_mv The impact of the Turkish population variome on the genomic architecture of rare disease traits
title The impact of the Turkish population variome on the genomic architecture of rare disease traits
spellingShingle The impact of the Turkish population variome on the genomic architecture of rare disease traits
Coban-Akdemir, Zeynep
Admixture
Consanguinity
Genomic architecture of rare disease traits
Runs of homozygosity
Turkish population
title_short The impact of the Turkish population variome on the genomic architecture of rare disease traits
title_full The impact of the Turkish population variome on the genomic architecture of rare disease traits
title_fullStr The impact of the Turkish population variome on the genomic architecture of rare disease traits
title_full_unstemmed The impact of the Turkish population variome on the genomic architecture of rare disease traits
title_sort The impact of the Turkish population variome on the genomic architecture of rare disease traits
dc.creator.none.fl_str_mv Coban-Akdemir, Zeynep
Song, Xiaofei
Ceballos, Francisco C
Pehlivan, Davut
Karaca, Ender
Bayram, Yavuz
Mitani, Tadahiro
Gambin, Tomasz
Bozkurt-Yozgatli, Tugce
Jhangiani, Shalini N
Muzny, Donna M
Lewis, Richard A
Liu, Pengfei
Boerwinkle, Eric
Hamosh, Ada
Gibbs, Richard A
Sutton, V Reid
Sobreira, Nara
Carvalho, Claudia M B
Shaw, Chad A
Posey, Jennifer E
Valle, David
Lupski, James R
author Coban-Akdemir, Zeynep
author_facet Coban-Akdemir, Zeynep
Song, Xiaofei
Ceballos, Francisco C
Pehlivan, Davut
Karaca, Ender
Bayram, Yavuz
Mitani, Tadahiro
Gambin, Tomasz
Bozkurt-Yozgatli, Tugce
Jhangiani, Shalini N
Muzny, Donna M
Lewis, Richard A
Liu, Pengfei
Boerwinkle, Eric
Hamosh, Ada
Gibbs, Richard A
Sutton, V Reid
Sobreira, Nara
Carvalho, Claudia M B
Shaw, Chad A
Posey, Jennifer E
Valle, David
Lupski, James R
author_role author
author2 Song, Xiaofei
Ceballos, Francisco C
Pehlivan, Davut
Karaca, Ender
Bayram, Yavuz
Mitani, Tadahiro
Gambin, Tomasz
Bozkurt-Yozgatli, Tugce
Jhangiani, Shalini N
Muzny, Donna M
Lewis, Richard A
Liu, Pengfei
Boerwinkle, Eric
Hamosh, Ada
Gibbs, Richard A
Sutton, V Reid
Sobreira, Nara
Carvalho, Claudia M B
Shaw, Chad A
Posey, Jennifer E
Valle, David
Lupski, James R
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos)
NIH - National Institute of Neurological Disorders and Stroke (NINDS) (Estados Unidos)
NIH - National Human Genome Research Institute (NHGRI) (Estados Unidos)
Baylor Scott & White Research Institute (Estados Unidos)
dc.subject.none.fl_str_mv Admixture
Consanguinity
Genomic architecture of rare disease traits
Runs of homozygosity
Turkish population
topic Admixture
Consanguinity
Genomic architecture of rare disease traits
Runs of homozygosity
Turkish population
description Purpose: The variome of the Turkish (TK) population, a population with a considerable history of admixture and consanguinity, has not been deeply investigated for insights on the genomic architecture of disease. Methods: We generated and analyzed a database of variants derived from exome sequencing data of 773 TK unrelated, clinically affected individuals with various suspected Mendelian disease traits and 643 unaffected relatives. Results: Using uniform manifold approximation and projection, we showed that the TK genomes are more similar to those of Europeans and consist of 2 main subpopulations: clusters 1 and 2 (N = 235 and 1181, respectively), which differ in admixture proportion and variome (https://turkishvariomedb.shinyapps.io/tvdb/). Furthermore, the higher inbreeding coefficient values observed in the TK affected compared with unaffected individuals correlated with a larger median span of long-sized (>2.64 Mb) runs of homozygosity (ROH) regions (P value = 2.09e-18). We show that long-sized ROHs are more likely to be formed on recently configured haplotypes enriched for rare homozygous deleterious variants in the TK affected compared with TK unaffected individuals (P value = 3.35e-11). Analysis of genotype-phenotype correlations reveals that genes with rare homozygous deleterious variants in long-sized ROHs provide the most comprehensive set of molecular diagnoses for the observed disease traits with a systematic quantitative analysis of Human Phenotype Ontology terms. Conclusion: Our findings support the notion that novel rare variants on newly configured haplotypes arising within the recent past generations of a family or clan contribute significantly to recessive disease traits in the TK population.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-01-01
2024
2024-01-01
2025
2025-03-31
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/26595
url https://hdl.handle.net/20.500.12105/26595
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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