The Interplay between natural selection and susceptibility to melanoma on allele 374F of SLC45A2 gene in a south European population
We aimed to study the selective pressures interacting on SLC45A2 to investigate the interplay between selection and susceptibility to disease. Thus, we enrolled 500 volunteers from a geographically limited population (Basques from the North of Spain) and by resequencing the whole coding region and i...
| Autores: | , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
| Repositorio: | r-FISABIO. Repositorio Institucional de Producción Científica |
| OAI Identifier: | oai:fisabio.fundanetsuite.com:p13615 |
| Acceso en línea: | https://fisabio.portalinvestigacion.com/publicaciones/13615 https://www.scopus.com/inward/record.uri?eid=2-s2.0-84905647852&doi=10.1371%2fjournal.pone.0104367&partnerID=40&md5=6ecca1fb41b4afccb5c9fa0d54d07d91 |
| Access Level: | acceso abierto |
| Palabra clave: | Alleles Antigens, Neoplasm Europe European Continental Ancestry Group Gene Frequency Gene-Environment Interaction Genetic Predisposition to Disease Haplotypes Humans Melanoma Membrane Transport Proteins Open Reading Frames Polymorphism, Single Nucleotide Quantitative Trait, Heritable Selection, Genetic Sequence Analysis, DNA Spain carrier protein SLC45A2 protein, human tumor antigen age distribution article cancer susceptibility depigmentation exon eye color gene frequency gene locus genetic variability genotype geographic distribution hair color haplotype human intron major clinical study melanoma nucleotide sequence oncogene population research single nucleotide polymorphism skin pigmentation SLC45A2 gene allele Caucasian DNA sequence genetic predisposition genetic selection genetics genotype environment interaction open reading frame quantitative trait |
| Sumario: | We aimed to study the selective pressures interacting on SLC45A2 to investigate the interplay between selection and susceptibility to disease. Thus, we enrolled 500 volunteers from a geographically limited population (Basques from the North of Spain) and by resequencing the whole coding region and intron 5 of the 34 most and the 34 least pigmented individuals according to the reflectance distribution, we observed that the polymorphism Leu374Phe (L374F, rs16891982) was statistically associated with skin color variability within this sample. In particular, allele 374F was significantly more frequent among the individuals with lighter skin. Further genotyping an independent set of 558 individuals of a geographically wider population with known ancestry in the Spanish population also revealed that the frequency of L374F was significantly correlated with the incident UV radiation intensity. Selection tests suggest that allele 374F is being positively selected in South Europeans, thus indicating that depigmentation is an adaptive process. Interestingly, by genotyping 119 melanoma samples, we show that this variant is also associated with an increased susceptibility to melanoma in our populations. The ultimate driving force for this adaptation is unknown, but it is compatible with the vitamin D hypothesis. This shows that molecular evolution analysis can be used as a useful technology to predict phenotypic and biomedical consequences in humans. © 2014 López et al. |
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