Identification of genes and biological pathways involved in human skin pigmentation variability in an evolutionary framework

Resumen

The aim of this work was to identify genetic variants and selective pressures that canaccount for the normal variability of human skin pigmentation.A Genome-Wide Association Study (GWAS) revealed new promising candidatevariants that could explain the variability of skin tonality: SNPs (Single NucleotidePolymorphism) in EXOC6B, ROBO2, IL5 and GPC6, and CNPs (Copy NumberPolymorphism) in regions containing the genes MIF, DDT y SORCS3. In addition,using the MAPH (Multiplex Amplifiable Probe Hybridization) technique 2 new CNVs(Copy Number Variants) were identified in the gene SLC24A5: in exon 1and in 5¿promoter region.Furthermore, we demonstrated that natural selection is favouring alleles 374F ofSLC45A2 and 60L of MC1R, associated with the depigmentation process of Europeanpopulations, but at the same time, with an increased susceptibility to melanoma.Using cell cultures of melanocytes from light- and dark-skinned individuals wedemonstrated that they behave differently in response to ultraviolet irradiation, both ata proliferative and gene expression levels. In addition, we propose that ribosomalproteins, MDM2 and P53 signaling pathway are involved in the response to ultravioletirradiation in both cell types.