Admixture has shaped romani genetic diversity in clinically relevant variants
Font-Porterias, Neus (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Giménez, Aaron (Universitat Autònoma de Barcelona)
Carballo-Mesa, Annabel (Universitat de Barcelona)
Calafell, Francesc (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Comas, D. (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)

Data:	2021
Resum:	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.
Ajuts:	Agencia Estatal de Investigación PID2019-106485GBI00 Agencia Estatal de Investigación CEX2018-000792-M
Nota:	Altres ajuts: FPU17/03501
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Romani ; Whole-exome sequences ; Clinically relevant variants ; Drug-response variants ; Local ancestry inference ; Eurocentric bias
Publicat a:	Frontiers in genetics, Vol. 12 (june 2021) , ISSN 1664-8021

DOI: 10.3389/fgene.2021.683880
PMID: 34220960

12 p, 568.9 KB

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