Molecular genetic studies on Behcet's disease

In order to investigate the molecular genetic mechanism of Behcet‘s disease，we studied the HLA-B region which is located on the short arm of chromosome6(6p21.3)。A YAC clone，Y109，was isolated from the YAC library using HLA class I specific primers.We investigated the new genes around the HLA-B which are in linkage disequilibrium with HLA-B I D1*I D15101.Y109was found to span 600kb.This region was confirmed to contain NOB1，NOB2，NOB3，MICA and MICB，which are non-HLA genes.Investigation of MICB polymorphism by PCR-SSP showed no significant association with Behcet‘s diseasease.In contrast，the frequency of MICA-A6was significantly higher in the patients than in the normal controls.Furthermore，investigation of amino acids in the peptide binding region of MICA-A6(Exon3)showed that they were all valine at position122.Studies on the other gene regions near the telomere on6p showed weak association with Behcet‘s disease，and it was concluded that the rescet cible gene for Behcet’disease‘s disease，the frequency of MICA-A6was significantly higher in the patients than in the normal controls.Establishment of transgenic animals of HLA-B I D1*I D 15101-MICA-A6 are now in progress in our laboratory，to elucidate the exact molecular genetic mechanism of this difficult disease.

In order to investigate the molecular genetic mechanism of Behcet's disease, we studied the HLA-B region which is located on the short arm of chromosome 6 (6p21.3). A YAC clone, Y109, was isolated from the YAC library using HLA class I specific primers. We investigated the new genes around the HLA-B which are in linkage disequilibrium with HLA-BィイD1*ィエD15101.Y109 was found to span 600kb. This region was confirmed to contain NOB1, NOB2, NOB3, MICA and MICB, which are non-HLA genes. Investigation of MICB polymorphism by PCR-SSP showed no significant association with Behcet's disease. In contrast, the frequency of MICA-A6 was significantly higher in the patients than in the normal controls.Furthermore, investigation of amino acids in the peptide binding region of MICA-A6 (exon 3) showed that they were all valine at position 122.Studies on the other gene regions near the telomere on 6p showed weak association with Behcet's disease, and it was concluded that the responsible gene for Behcet's disease is located in the 230 kb between HLA-C and MICB.Further studies on the association of Behcet's disease with these new genes are indicated. Establishment of transgenic animals of HLA-BィイD1*ィエD15101-MICA-A6 are now in progress in our laboratory, to elucidate the exact molecular genetic mechanism of this difficult disease.