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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Acosta, Jose Luis Hernández-Mondragón, Alma Cristal Correa-Acosta, Laura Carolina Cazañas-Padilla, Sandra Nathaly Chávez-Florencio, Berenice Ramírez-Vega, Elvia Yamilet Monge-Cázares, Tulia Aguilar-Salinas, Carlos A. Tusié-Luna, Teresa del Bosque-Plata, Laura |
| Abstract | Background Genetic variations of the TCF7L2 gene are associated with the development of Type 2 diabetes (T2D). The associated mutations have demonstrated an adaptive role in some human populations, but no studies have determined the impact of evolutionary forces on genetic diversity in indigenous populations from Mexico. Here, we sequenced and analyzed the variation of the TCF7L2 gene in three Amerindian populations and compared the results with whole-exon-sequencing of Mestizo populations from Sigma and the 1000 Genomes Project to assess the roles of selection and recombination in diversity. Results The diversity in the indigenous populations was biased to intronic regions. Most of the variation was low frequency. Only mutations rs77961654 and rs61724286 were located on exon 15. We did not observe variation in intronic region 4–6 in any of the three indigenous populations. In addition, we identified peaks of selective sweeps in the mestizo samples from the Sigma Project within this region. By replicating the analysis of association with T2D between case-controls from the Sigma Project, we determined that T2D was most highly associated with the rs7903146 risk allele and to a lesser extent with the other six variants. All associated markers were located in intronic region 4–6, and their r2 values of linkage disequilibrium were significantly higher in the Mexican population than in Africans from the 1000 Genomes Project. We observed reticulations in both the haplotypes network analysis from seven marker associates and the neighborNet tree based on 6061 markers in the TCF7L2 gene identified from all samples of the 1000 Genomes Project. Finally, we identified two recombination hotspots in the upstream region and 3’ end of the TCF7L2 gene. Conclusions The lack of diversity in intronic region 4–6 in Indigenous populations could be an effect of selective sweeps generated by the selection of neighboring rare variants at T2D-associated mutations. The survivors’ variants make the intronic region 4–6 the area of the greatest population differentiation within the TCF7L2 gene. The abundance of selective peak sweeps in the downstream region of the TCF7L2 gene suggests that the TCF7L2 gene is part of a region that is in constant recombination between populations. |
| Related Links | https://bmcgenomdata.biomedcentral.com/counter/pdf/10.1186/s12863-016-0372-7.pdf |
| Ending Page | 15 |
| Page Count | 15 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 27306844 |
| DOI | 10.1186/s12863-016-0372-7 |
| Journal | BMC Genomic Data |
| Issue Number | 1 |
| Volume Number | 17 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2016-05-26 |
| Access Restriction | Open |
| Subject Keyword | Life Sciences Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Genetics and Population Dynamics TCF7L2 gene Type 2 diabetes Genetic association Sweeps selection Recombination hotspots |
| Content Type | Text |
| Resource Type | Article |
| Subject | Health Informatics Genetics |
| Journal Impact Factor | 1.9/2023 |
| 5-Year Journal Impact Factor | 1.9/2023 |
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