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

Genetic isolates represent exceptional resources for the mapping of complex traits but not all isolates are similar. We have selected a genetic and cu ltural isolate, the village of Talana from an isolated area of Sardinia, an d propose that this population is suitable for the mapping of complex trait s. A wealth of historical and archive data allowed the reconstruction of th e demographic and genealogical history of the village. Key features of the population, which has grown slowly with no significant immigration, were de fined by using a combination of historical, demographic and genetic studies . The genealogy of each Talana inhabitant was reconstructed and the main ma ternal and paternal lineages of the village were defined. Haplotype and phy logenetic analyses of the Y chromosome and characterisation of mitochondria l DNA haplogroups were used to determine the number of ancestral village fo unders. The extent of linkage disequilibrium (LD) was evaluated by the anal ysis of several microsatellites in chromosomal region Xq13.3, which was pre viously used to asses the extension of LD. Genealogical reconstructions wer e confirmed and reinforced by the genetic analyses, since some lineages wer e found to have merged prior to the beginning of the archival records, sugg esting an even smaller number of founders than initially predicted. About 8 0% 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-M b region in Xq13.3. This suggests the possibility of identifying identical- by-descent regions associated with complex traits in a genome-wide search b y using a low-density marker map. The present study emphasises the importan ce of combining genetic studies with genealogical and historical informatio n.