caa a22 4500 469033398 CHVBK 20180323132749.0 cr unu---uuuuu 170328e19920901xx s 000 0 eng 10.1007/BF00218041 doi (NATIONALLICENCE)springer-10.1007/BF00218041 Ancestral haplotypes reveal the role of the central MHC in the immunogenetics of IDDM [Elektronische Daten] [Mariapia Degli-Esposti, Lawrence Abraham, Vincent McCann, Thomas Spies, Frank Christiansen, Roger Dawkins] The major histocompatibility complex (MHC) contains multiple and diverse genes which may be relevant to the induction adn regulation of autoimmune responses in insulin dependent diabetes mellitus (IDDM). In addition to HLA class I and II, the possible candidates include TNF, C4, and several other poorly defined polymorphic genes in the central MHC region. This study describes two approaches which take advantage of the fact that the relevant genes are carried by highly conserved ancestral haplotypes such as 8.1 (HLA-B8, TNFS, C4AQO, C4B1, DR3, DQ2). First, three "diabetogenic” haplotypes (two Caucasoid and one Mongoloid) have been compared and it has been shown that all three share a rare allele of BAT3 as well as sharing DR3, DQ2. In 43 sequential patients with IDDM the cross product ration for BAT3S was 4.8 (p<0.01) and 6.9 for HLA-B8 plus BAT3S (p<0.001). Second, partial or recombinant ancestral haplotypes with either HLA class I (HLA-B8) or II (HLA-DR3, DQ2) alleles were identified. Third, using haplotypic polymorphisms such as the one in BAT3, we have shown that all the patients carrying recombinants of the 8.1 ancestral haplotype share the central region adjacent to HLA-B. These findings suggest that both HLA and non-HLA genes are involved in conferring susceptibility to IDDM, and that the region between HLA-B and BAT3 contains some of the relevant genes. By contrast, similar approaches suggest that protective genes map to the HLA class II region. Springer-Verlag, 1992 Degli-Esposti Mariapia Department of Clinical Immunology, Royal Perth Hospital, GPO Box X2213, 6001, Perth, Western Australia aut Abraham Lawrence Department of Clinical Immunology, Royal Perth Hospital, GPO Box X2213, 6001, Perth, Western Australia aut McCann Vincent Diabetic Unit, Royal Perth Hospital, 6001, Perth, Western Australia aut Spies Thomas Dana Faber Cancer Institute, 02115, Boston, MA, USA aut Christiansen Frank Department of Clinical Immunology, Royal Perth Hospital, GPO Box X2213, 6001, Perth, Western Australia aut Dawkins Roger Department of Clinical Immunology, Royal Perth Hospital, GPO Box X2213, 6001, Perth, Western Australia aut Immunogenetics Springer-Verlag 36/6(1992-09-01), 345-356 0093-7711 36:6<345 1992 36 251 https://doi.org/10.1007/BF00218041 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00218041 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Degli-Esposti Mariapia Department of Clinical Immunology, Royal Perth Hospital, GPO Box X2213, 6001, Perth, Western Australia aut NATIONALLICENCE 700 1- Abraham Lawrence Department of Clinical Immunology, Royal Perth Hospital, GPO Box X2213, 6001, Perth, Western Australia aut NATIONALLICENCE 700 1- McCann Vincent Diabetic Unit, Royal Perth Hospital, 6001, Perth, Western Australia aut NATIONALLICENCE 700 1- Spies Thomas Dana Faber Cancer Institute, 02115, Boston, MA, USA aut NATIONALLICENCE 700 1- Christiansen Frank Department of Clinical Immunology, Royal Perth Hospital, GPO Box X2213, 6001, Perth, Western Australia aut NATIONALLICENCE 700 1- Dawkins Roger Department of Clinical Immunology, Royal Perth Hospital, GPO Box X2213, 6001, Perth, Western Australia aut NATIONALLICENCE 773 0- Immunogenetics Springer-Verlag 36/6(1992-09-01), 345-356 0093-7711 36:6<345 1992 36 251 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer