|
|||||
|
|
Localization of central MHC genes influencing type I diabetes |
|
| Authors: | Karey Y Cheong Richard J N Allcock Peter Eerligh Campbell S Witt Frank T Christiansen Vincent McCann Patricia Price |
| Institution: | a Department of Clinical Immunology and Biochemical Genetics (K.Y.C., R.J.N.A., C.S.W., F.T.C., P.P.), Perth, Australia b Department of Pathology (K.Y.C., R.J.N.A., F.T.C., P.P.), University of Western Australia, Perth, Australia c Department of Immunohaematology and Blood Transfusion (P.E.), Leiden University Medical Centre, Leiden, The Netherlands d Department of Endocrinology and Diabetes (V.M.), Royal Perth Hospital, Perth, Australia |
| Abstract: | The contribution of MHC class II haplotypes to susceptibility to type I diabetes has been clearly established, and interest has now focused on the effects of additional genes in the MHC region. We have investigated the central MHC alleles on 8.1 ancestral haplotype (HLA-A1, B8, DR3, DQ2), as it is well conserved in Caucasian populations. The HLA-DR3-DQ2 genotype is a recognized risk factor for type I diabetes. Single nucleotide polymorphisms and microsatellites in the MHC were used to map segments of the 8.1 ancestral haplotype carried by type I diabetic and control subjects expressing either HLA-B8 or DR3, but not both these markers. In this way we controlled for the diabetogenic effect of carriage of DR3. Alleles of the 8.1 ancestral haplotype between TNFA-308/D6STNFa and HLA-B were carried with significantly greater frequency in B8?, DR3+ type I diabetic patients compared with B8?, DR3+ controls. This interval was marked by a BAT1 gene polymorphism and a MIB microsatellite allele. |
| Keywords: | ancestral haplotype HLA MHC microsatellite type I diabetes |
| 本文献已被 ScienceDirect 等数据库收录！ | |