Admixture has shaped romani genetic diversity in clinically relevant variants

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• dc.contributor.author Font-Porterias, Neus
• dc.contributor.author Giménez, Aaron
• dc.contributor.author Carballo Mesa, Annabel
• dc.contributor.author Calafell i Majó, Francesc
• dc.contributor.author Comas, David, 1969-
• dc.date.accessioned 2021-08-25T06:55:48Z
• dc.date.available 2021-08-25T06:55:48Z
• dc.date.issued 2021
• dc.description.abstract Genetic patterns of inter-population variation are a result of different demographic and adaptive histories, which gradually shape the frequency distribution of the variants. However, the study of clinically relevant mutations has a Eurocentric bias. The Romani, the largest transnational minority ethnic group in Europe, originated in South Asia and received extensive gene flow from West Eurasia. Most medical genetic studies have only explored founder mutations related to Mendelian disorders in this population. Here we analyze exome sequences and genome-wide array data of 89 healthy Spanish Roma individuals to study complex traits and disease. We apply a different framework and focus on variants with both increased and decreased allele frequencies, taking into account their local ancestry. We report several OMIM traits enriched for genes with deleterious variants showing increased frequencies in Roma or in non-Roma (e.g., obesity is enriched in Roma, with an associated variant linked to South Asian ancestry; while non-insulin dependent diabetes is enriched in non-Roma Europeans). In addition, previously reported pathogenic variants also show differences among populations, where some variants segregating at low frequency in non-Roma are virtually absent in the Roma. Lastly, we describe frequency changes in drug-response variation, where many of the variants increased in Roma are clinically associated with metabolic and cardiovascular-related drugs. These results suggest that clinically relevant variation in Roma cannot only be characterized in terms of founder mutations. Instead, we observe frequency differences compared to non-Roma: some variants are absent, while other have drifted to higher frequencies. As a result of the admixture events, these clinically damaging variants can be traced back to both European and South Asian-related ancestries. This can be attributed to a different prevalence of some genetic disorders or to the fact that genetic susceptibility variants are mostly studied in populations of European descent, and can differ in individuals with different ancestries.
• dc.format.mimetype application/pdf
• dc.identifier.citation Font-Porterias N, Giménez A, Carballo-Mesa A, Calafell F, Comas D. Admixture has shaped romani genetic diversity in clinically relevant variants. Front Genet. 2021;12:683880. DOI: 10.3389/fgene.2021.683880
• dc.identifier.doi http://dx.doi.org/10.3389/fgene.2021.683880
• dc.identifier.issn 1664-8021
• dc.identifier.uri http://hdl.handle.net/10230/48328
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Front Genet. 2021;12:683880
• dc.rights © 2021 Font-Porterias, Giménez, Carballo-Mesa, Calafell and Comas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Eurocentric bias
• dc.subject.keyword Romani
• dc.subject.keyword Clinically relevant variants
• dc.subject.keyword Drug-response variants
• dc.subject.keyword Local ancestry inference
• dc.subject.keyword Whole-exome sequences
• dc.title Admixture has shaped romani genetic diversity in clinically relevant variants
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion