Signatures of human adaptation in quantitative trait loci influencing micronutrient homeostasis in liver
| Autor: | Engelken, Johannes, Scherr, Anna-Lena, Jiménez-Álvarez, Victoria, Codina-Solà, Marta, Medina-Stacey, Daniel, Spataro, Nino, Calafell, Francesc, Bosch, Elena |
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| Rok vydání: | 2016 |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Engelken, Johannes.-- Trabajo presentado en el V Congreso de la Sociedad Española de Biología Evolutiva (SESBE 2016), celebrado en Murcia del 18 al 21 de enero de 2016. Micronutrients possess vital functions at molecular, cellular and physiological levels, and they are tightly regulated in the human body. In order to assess variability and potential adaptive evolution of trace element homeostasis, we quantified 18 trace elements in 150 human liver samples, together with the expression levels of 90 genes and abundances of 40 proteins involved in their homeostasis. Additionally, we genotyped 169 SNPs in the same sample set. We detected significant associations between SNP genotypes and eight protein abundances (pQTLs), 10 mRNA levels (eQTLs) and 15 micronutrient concentrations (nutriQTLs). Six of these survived the false discovery rate (FDR) cutoff: i) one pQTL for GPX2 (rs10133290); ii) two previously described eQTLs for HFE (rs12346) and SELO (rs4838862) expression; and iii) three nutriQTLs: the pathogenic C282Y mutation at HFE affecting iron (rs1800562), and two SNPs within several clustered metallothionein genes determining selenium concentration (rs1811322 and rs904773). Within the complete set of significant QTLs (which involved 30 SNPs and 20 gene regions), we identified 12 SNPs with extreme patterns of population differentiation (FST values in the top 5% percentile in at least one HapMap population pair) and significant evidence for selective sweeps involving QTLs at GPX1, SELENBP1 GPX3, SLC30A9 and SLC39A8, which are related to zinc and selenium. Overall, this multilayered, integrative study of various molecular phenotypes illustrates the role of regulatory variants in explaining differences in trace element homeostasis among populations and in the human adaptive response to environmental pressures related to micronutrients. |
| Databáze: | OpenAIRE |
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