دورية أكاديمية
Rare intronic variants of TCF7L2 arising by selective sweeps in an indigenous population from Mexico.
العنوان: | Rare intronic variants of TCF7L2 arising by selective sweeps in an indigenous population from Mexico. |
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المؤلفون: | Acosta JL; Departamento de Microbiología y Patología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada No. 950, Puerta 7, Edificio O, Planta Baja, Col. Independencia, 44340 Guadalajara, Jalisco, Mexico.; Instituto Politécnico Nacional, Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional (CIIDIR)-Unidad, Blvd, Juan de Dios Bátiz Paredes #250, 81101 Sinaloa, Mexico., Hernández-Mondragón AC; Laboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, 14610 Mexico City, Mexico., Correa-Acosta LC; Laboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, 14610 Mexico City, Mexico., Cazañas-Padilla SN; Laboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, 14610 Mexico City, Mexico., Chávez-Florencio B; Laboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, 14610 Mexico City, Mexico., Ramírez-Vega EY; Laboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, 14610 Mexico City, Mexico., Monge-Cázares T; Laboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, 14610 Mexico City, Mexico., Aguilar-Salinas CA; Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición, Vasco de Quiroga 15, 14000 Mexico City, Mexico., Tusié-Luna T; Instituto de Investigaciones Biomédicas, UNAM, Unidad de Biología Molecular y Medicina Genómica, UNAM/INCMNSZ, 04510 Mexico City, Mexico., Del Bosque-Plata L; Laboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica, Periférico Sur No. 4809, Col. Arenal Tepepan, 14610 Mexico City, Mexico. ldelbosque@inmegen.gob.mx. |
المصدر: | BMC genetics [BMC Genet] 2016 May 26; Vol. 17 (1), pp. 68. Date of Electronic Publication: 2016 May 26. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 100966978 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2156 (Electronic) Linking ISSN: 14712156 NLM ISO Abbreviation: BMC Genet Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : BioMed Central, [2000- |
مواضيع طبية MeSH: | Polymorphism, Genetic*, Ethnicity/*genetics , Introns/*genetics , Transcription Factor 7-Like 2 Protein/*genetics, Diabetes Mellitus, Type 2/genetics ; Exons/genetics ; Humans ; Mexico/ethnology ; Mutation ; Recombination, Genetic |
مستخلص: | 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 r(2) 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. |
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فهرسة مساهمة: | Keywords: Genetic association; Recombination hotspots; Sweeps selection; TCF7L2 gene; Type 2 diabetes |
المشرفين على المادة: | 0 (Transcription Factor 7-Like 2 Protein) |
تواريخ الأحداث: | Date Created: 20160528 Date Completed: 20170913 Latest Revision: 20220321 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC4880969 |
DOI: | 10.1186/s12863-016-0372-7 |
PMID: | 27230431 |
قاعدة البيانات: | MEDLINE |
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