Caratterizzazione della struttura genetica della popolazione di Campora

Abstract

Study of a genetically isolated human population. We aim to study complex traits (mostly cardiovascular diseases) using isolated population as model study. We identified a village (Campora) that could be considered a good candidate as model study due to empirical evidences of geographical isolation. In this study we confirm these evidences with the analysis of the genetic structure of the population. We found the presence of the main features of isolated population: small number of founders, increased homozigosity and extended region of linkage disequilibrium. Data from the registry office were collected, and we were able to build a pedigree spanning the last four centuries which includes about 11000 individuals. In this pedigree we determined the number of independent maternal and paternal lineages that gave rise to the current population according to pedigree data. We used the lineages as a starting point for the determination of the number of founders from which the current population derives, using molecular marker analysis. The determination of female founders was done using both sequence and restriction polymorphisms of the mtDNA. We found that 93% of the current female native population derives from 17 female founders. The determination of male founders was carried out using polymorphisms of the Y chromosome. We found that 90% of the current native male population derives from 20 male founders It has been well demonstrated that isolated populations show extended regions of Linkage Disequilibrium (LD) as a consequence of the general increased homozygosity. Therefore, we first characterized in the Campora population the region on Xq13 that had already been analyzed in different kinds of populations including both isolated and open populations and then we evaluated the extend of LD in the whole genome. In both cases we find out that in Campora LD extends over longer distance respect to outbred populations. All these experimental evidences confirm the empirical ones and allow us to consider Campora as a good model of genetic isolated population.