Dataset Information

Whole-exome analysis in Tunisian Imazighen and Arabs shows the impact of demography in functional variation

ABSTRACT: Human 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.

SUBMITTER: Lucas-Sanchez M

PROVIDER: S-EPMC8548440 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundA family history of breast cancer has long been thought to indicate the presence of inherited genetic events that predispose to this disease. In North Africa, many specific epidemio-genetic characteristics have been observed in breast cancer families when compared to Western populations. Despite these specificities, the majority of breast cancer genetics studies performed in North Africa remain restricted to the investigation of the BRCA1 and BRCA2 genes. Thus, comprehensive data at a whole exome or whole genome level from local patients are lacking.MethodsA whole exome sequencing (WES) of seven breast cancer Tunisian families have been performed using a family-based approach. We focused our analysis on BC-TN-F001 family that included two affected members that have been sequenced using WES. Relevant variants identified in BC-TN-F001 have been confirmed using Sanger sequencing. Then, we conducted an integrative analysis by combining our results with those from other WES studies in order to figure out the genetic transmission model of the newly identified genes. Biological network construction and protein-protein interactions analyses have been performed to decipher the molecular mechanisms likely accounting for the role of these genes in breast cancer risk.ResultsSequencing, filtering strategies, and validation analysis have been achieved. For BC-TN-F001, no deleterious mutations have been identified on known breast cancer genes. However, 373 heterozygous, exonic and rare variants have been identified on other candidate genes. After applying several filters, 12 relevant high-risk variants have been selected. Our results showed that these variants seem to be inherited in a family specific model. This hypothesis has been confirmed following a thorough analysis of the reported WES studies. Enriched biological process and protein-protein interaction networks resulted in the identification of four novel breast cancer candidate genes namely MMS19, DNAH3, POLK and KATB6.ConclusionsIn this first WES application on Tunisian breast cancer patients, we highlighted the impact of next generation sequencing technologies in the identification of novel breast cancer candidate genes which may bring new insights into the biological mechanisms of breast carcinogenesis. Our findings showed that the breast cancer predisposition in non-BRCA families may be ethnic and/or family specific.

Dataset Information

Whole-exome analysis in Tunisian Imazighen and Arabs shows the impact of demography in functional variation

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets