Human Molecular Genetics, 2000, Vol. 9, No. 20 2959-2965
© 2000 Oxford University Press
The inter-regional distribution of HLA class II haplotypes indicates the suitability of the Sardinian population for case–control association studies in complex diseases
1Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Ospedale Microcitemico, Via Jenner, Cagliari 09121, Italy, 2Dipartimento di Zoologia e Antropologia Biologica, Università di Sassari, Sassari 07100, Italy, 3Servizio di Diabetologia Pediatrica, Ospedale G. Brotzu, Cagliari 09121, Italy, 4Dipartimento di Neuroscienze, Università di Cagliari, Ospedale Binaghi, Cagliari 09121, Italy and 5Wellcome Trust Centre for Molecular Mechanisms in Disease, University of Cambridge, Addenbrookes Hospital, Cambridge CB2 2XY, UK
We have analysed HLA class II gene-based substructure of the Sardinian population in order to evaluate the possible influence of this parameter in the mapping of common disease loci using association methods. We first examined the distribution of the HLA-DRB1-DQA1-DQB1 haplotypes in 631 newborns from seven different regions of the island, and found that the most frequent haplotypes were uniformly distributed in all regions, but at frequencies unique to Sardinia. Other haplotypes, common in other white European populations, are consistently rare or absent across the whole island. Analysis of molecular variance (AMOVA) showed a very low degree of genetic differentiation between the coastal regions, which have suffered repeated invasions over many years, and the most internal and isolated part of the island. This suggests that there has been little genetic flow from the various populations that have invaded the island during the last 3000 years and that Sardinia is a relatively homogeneous population. The validity of these unrelated control HLA haplotype frequencies and our claim of homogeneity were established by demonstrating the near identity of the affected family-based control (AFBAC) HLA haplotype frequencies in 243 type 1 diabetes and 495 multiple sclerosis families from Sardinia and those of the unrelated controls. These results indicate that robust case–control studies can be carried out in Sardinia offering cost efficiency over certain family-based designs.
+ These authors contributed equally to this work
§ To whom correspondence should be addressed. Tel: +39 070 6095681; Fax: +39 070 6095558; Email: fcucca@mcweb.unica.it
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