Abstract
Basques show specific cultural, demographic, and genetic characteristics that have placed them as an isolated and unique population within Europe, such as their non-Indo-European language, Euskara. They have historically lived along the Western Pyrenees, between Spain and France, in one of the most important European glacial refugia during the Last Glacial Maximum. The most striking genetic characteristic is their highest frequency of the RhD blood group negative allele, a variant related to the hemolytic disease of the newborn. Both demographic and adaptive processes have been suggested as possible causes of the high frequency of RhD negative in Basques, but neither hypothesis has been clearly demonstrated. While previous studies on the Rh system in Basques have been mostly focused on serological and genotyping diversity, in this work we analyze genotyping and next generation sequencing data in order to provide a general framework of the genetic scenario of the system in Basques. In particular, we genotyped the most relevant variants of the system (D/d, E/e, and C/c), and sequenced three ~6 kb flanking regions surrounding the Rh genes in Basques and also in other populations for comparison. Our results are in agreement with previous studies, with Basques presenting the highest frequency of the RHD deletion (47.2%). Haplotype analyses of D/d, E/e, and C/c variants confirmed an association between the RhC allele, previously suggested to be under positive selection, and the RhD positive variant in non-sub-Saharan populations, including Basques. We also found extreme differentiation for the C/c variant when comparing sub-Saharan to non-sub-Saharan populations.
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Acknowledgements
The authors acknowledge all the volunteers participating in the study. We thank the Genomics Facility of the “Universitat Pompeu Fabra” for their technical help. We also thank Yali Xue for providing details of the sequencing primers. A.F-B was supported with a FI fellowship from the Generalitat de Catalunya (FI-DGR 2016). This work was supported by the “Agencia Estatal de Investigación” (AEI) of the “Ministerio de Economía, Industria y Competitividad” (MINEICO) and “Fondo Europeo de Desarrollo Regional” (FEDER) with project grants CGL2016-75389-P and BFU2016-77961-P, the Unidad de Excelencia María de Maeztu (MDM-2014-0370) funded by the MINECICO, and by the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya” with the grant GRC2014SGR866.
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Flores-Bello, A., Mas-Ponte, D., Rosu, M.E. et al. Sequence diversity of the Rh blood group system in Basques. Eur J Hum Genet 26, 1859–1866 (2018). https://doi.org/10.1038/s41431-018-0232-1
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DOI: https://doi.org/10.1038/s41431-018-0232-1
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