Archival, demographic and genetic studies define a Sardinian sub-isolate as a suitable model for mapping complex traits

Abstract.

Genetic isolates represent exceptional resources for the mapping of complex traits but not all isolates are similar. We have selected a genetic and cultural isolate, the village of Talana from an isolated area of Sardinia, and propose that this population is suitable for the mapping of complex traits. A wealth of historical and archive data allowed the reconstruction of the demographic and genealogical history of the village. Key features of the population, which has grown slowly with no significant immigration, were defined by using a combination of historical, demographic and genetic studies. The genealogy of each Talana inhabitant was reconstructed and the main maternal and paternal lineages of the village were defined. Haplotype and phylogenetic analyses of the Y chromosome and characterisation of mitochondrial DNA haplogroups were used to determine the number of ancestral village founders. The extent of linkage disequilibrium (LD) was evaluated by the analysis of several microsatellites in chromosomal region Xq13.3, which was previously used to asses the extension of LD. Genealogical reconstructions were confirmed and reinforced by the genetic analyses, since some lineages were found to have merged prior to the beginning of the archival records, suggesting an even smaller number of founders than initially predicted. About 80% of the present-day population appears to derive from eight paternal and eleven maternal ancestral lineages. LD was found to span, on average, a 5-Mb region in Xq13.3. This suggests the possibility of identifying identical-by-descent regions associated with complex traits in a genome-wide search by using a low-density marker map. The present study emphasises the importance of combining genetic studies with genealogical and historical information.