IP: Dr. Pedro Moral Castrillo

Resumen del proyecto: This project aims to explore the detailed variation of several human genome regions and its implications in order to approach the natural history of the gene susceptibility to disease and the biological history of human populations. To do this we propose the analysis of three genomic regions (100-250Kb each) corresponding to the oxide nitric synthases, NOS1, NOS2, and NOS3, and adjacent non-functional regions of similar size. Additional analyses will include other genomic regions (autosomal and Y-chromosome) to validate the population findings. This variation will be tested in a set of population samples covering the whole Mediterranean region, paying special attention to the easternmost part of this geographical area, and including also external reference populations. The molecular dissection of each region will be carried out throughout the analysis of a battery of SNPs (>25) and a set of closely associated STR, including genotyping and frequency, haplotype, and LD pattern analyses. An additional goal of this project is the assessment of the population variation of several STRs whose distribution has not been studied so far. The approach to epidemiological applications will include i) an analysis of genetic association in patients with ischemic heart disease form different Mediterranean countries (Spain, Tunisia, and Corsica, France), ii) estimates of the age of risk variants for cardiovascular disease and other relevant diseases from the literature, and iii) to assess for single or multiple origin of those risk variants in the Mediterranean regions, as well as the identification of potential selective events. From the population perspective, this project aims to i) analyze the variability of a set of SNP-STR compound systems and try to get new phylogenetic and demographical (migrations, gene flow, expansions, etc.) information on human populations, ii) complete the genetic/genomic information on the Mediterranean region , and iii) test for the usefulness of the autosomal SNP-STR systems for population purposes.

Entidad financiadora: Ministerio de Ciencia e Innovación