Lucas Sánchez, MarcelFont-Porterias, NeusCalafell i Majó, FrancescFadhlaoui-Zid, KarimaComas, David, 1969-2021-12-172021-12-172021Lucas-Sánchez M, Font-Porterias N, Calafell F, Fadhlaoui-Zid K, Comas D. Whole-exome analysis in Tunisian Imazighen and Arabs shows the impact of demography in functional variation. Sci Rep. 2021;11(1):21125. DOI: 10.1038/s41598-021-00576-02045-2322http://hdl.handle.net/10230/49241Human populations are genetically affected by their demographic history, which shapes the distribution of their functional genomic variation. However, the genetic impact of recent demography is debated. This issue has been studied in different populations, but never in North Africans, despite their relevant cultural and demographic diversity. In this study we address the question by analyzing new whole-exome sequences from two culturally different Tunisian populations, an isolated Amazigh population and a close non-isolated Arab-speaking population, focusing on the distribution of functional variation. Both populations present clear differences in their variant frequency distribution, in general and for putatively damaging variation. This suggests a relevant effect in the Amazigh population of genetic isolation, drift, and inbreeding, pointing to relaxed purifying selection. We also discover the enrichment in Imazighen of variation associated to specific diseases or phenotypic traits, but the scarce genetic and biomedical data in the region limits further interpretation. Our results show the genomic impact of recent demography and reveal a clear genetic differentiation probably related to culture. These findings highlight the importance of considering cultural and demographic heterogeneity within North Africa when defining population groups, and the need for more data to improve knowledge on the region's health and disease landscape.application/pdfeng© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-021-00576-0Biological anthropologyGenetic variationinfo:eu-repo/semantics/openAccess