Linkage mapping of a novel susceptibility locus for Behcet's disease to chromosome 6p22-23

Objective. The etiology of Behcet's disease is unknown; however, familial a ggregation studies indicate a strong genetic background and a complex inher itance model. Association of HLA-B51 with Behcet's disease is regarded as b eing the strongest evidence of genetic contribution described to date. A lo w rate of recombination was observed within the telomeric end of the major histocompatibility complex up to the HFE gene, which causes hereditary hemo chromatosis. We therefore hypothesized that the telomere of 6p may harbor a susceptibility gene for Behcet's disease. Methods. A series of 28 multicase families of Turkish origin was ascertaine d, and 78 of the 183 available family members were diagnosed as having Behc et's disease. For the analysis of the telomeric region adjacent to HLA-B, w e used a panel of 20 highly polymorphic microsatellite markers between D6S2 73 and D6S470, covering a region of similar to 36 cM. Results. Multipoint nonparametric linkage analysis using GeneHunter 2.0 sof tware revealed a broad peak of linkage, with the highest Z score of 4.11 at position D6S285, which is similar to 17 cM telomeric to HLA-B. Conclusion. This significant linkage finding may indicate a second suscepti bility locus in the telomere of chromosome 6p. Identification of this putat ive susceptibility gene could help to further understand the pathogenesis o f Behcet's disease.