The distribution of HLA class II haplotypes reveals that the Sardinian population is genetically differentiated from the other Caucasian populations

In this study we have established the frequencies of the DRB1-DQA1-DQB1 hap lotypes in a large cohort of Sardinian new-borns and found that the most fr equent haplotypes were detected at frequencies unique to the Sardinians. Ot her haplotypes, common in other Caucasian populations, are rare or absent a cross the island. Next, the DRB1-DQA1-DQB1 haplo-type frequencies obtained in Sardinians and those reported in other human populations were used to co mpute genetic distances and construct phylogenetic trees. A clear-cut patte rn appeared with a split between the three major human groups: Caucasians, Asians and Blacks. Among the Caucasians there were three major clusters: a group representing the North-Africans, a group including most of the Europe an-derived populations and a group encompassing Bulgaria, Greece and Sardin ia. When we increased the resolution of the tree using the genetic distance s calculated from both DRB1-DQA1-DQB1 haplotypes and class I HLA A, B, C al lelic frequencies, the Sardinians clearly emerged as the major outlier amon g the various European populations considered in this study. These results indicate that the genetic structure of the present Sardinian population is the result of a fixation of haplotypes, which are very rare elsewhere, and are most likely to have originated from a relatively large group of founder s.