Immunogenetics (2000) 51 : 383–386 Q Springer-Verlag 2000 BRIEF COMMUNICATION Margriet Snoek 7 Mark R. Albertella Marcel van Kooij 7 Joanne Wixon 7 Huub van Vugt Koen de Groot 7 R. Duncan Campbell G7c, a novel gene in the mouse and human major histocompatibility complex class III region, possibly controlling lung tumor susceptibility Received: 29 October 1999 / Revised: 28 December 1999 M. Snoek (Y) 7 M. van Kooij 7 H. van Vugt 7 K. de Groot Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands e-mail: snoek6nki.nl Tel.:c31-20-5122001 Fax: c31-20-5122011 M.R. Albertella 7 J. Wixon 7 R.D. Campbell MRC Immunochemistry Unit, Department of Biochemistry, Oxford University, South Parks Road, Oxford, OX1 3QU, UK Present address: M.R. Albertella, AstraZeneca Pharmaceuticals, Cancer and Infection Department, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK Present address: J. Wixon, Biochemistry Division, Stopford Building, University of Manchester, Manchester, M13 9PT, UK Present address: R.D. Campbell, HGMP Resource Centre, Hinxton Cambridge, CB10 15B, UK Key words MHC class III region 7 Mouse 7 Human 7 G7c 7 Lung tumor susceptibility The human major histocompatibility complex (MHC) is a F4-Mbp region of the genome located on the short arm of Chromosome (Chr) 6, in chromosomal band 6p21.3, while the mouse MHC is located on Chr 17 (18.4–20.5 cM). The MHC region has been well con- served throughout evolution, and contains the genes encoding the highly polymorphic class I and class II his- tocompatibility proteins, which fulfill important immu- nologic functions by presenting antigen to the T-cell re- ceptor of cytotoxic and T helper cells, respectively. The class I and class II genes are located in two clusters, separated by a gene-dense segment of DNA of approx- imately 1.1 Mbp in humans and 1 Mbp in the mouse. This region has been termed the class III region and contains a broad variety of mostly unrelated genes, ex- hibiting little polymorphic variation. More than 70 genes have been identified to date in an 800-kb region (MHC Sequencing Consortium 1999), including those encoding complement factors, heat shock proteins, and tumor necrosis factor (for an overview see Aguado et al. 1996). Comparison of the C4-H2D region in the mouse to the C4-HLAB region in humans has shown high synte- ny between the genes of the two species as demon- strated by the analysis of the neuraminidase gene Neu1 (G9) (Carrillo et al. 1997), the heat shock protein-en- coding gene cluster (Snoek et al. 1993, 1994), G7b (Olavesen et al. 1993), and G7a (Snoek and van Vugt 1999). Both the genomic organization as well as the se- quence of the coding regions of the genes shows strong conservation. A viral integration in the mouse MHC that has driven G7b and G7a apart (Snoek et al. 1996) disturbs the almost identical organization of this seg- ment of the class III region. The additional 15 kb of DNA present in the mouse contains remnants of gag and pol sequences flanking the G7e gene that resem- bles a viral envelope gene. Susceptibilities to a wide range of diseases, including Behcet’s disease, orchitis, insulin-dependent diabetes mellitus, rheumatoid arthritis, and certain forms of can- cer have been linked to the human MHC (Cucca and Todd 1996; Mizuki et al. 1995; Thomson 1988; Tiwari and Terasaki 1985; Tsuji et al. 1992). Many of these dis- ease susceptibilities may result from allelic differences in the class I and class II antigens. However, class III region genes might also be involved. In the mouse, sus- ceptibility to hormonally induced mammary cancer, chemically induced lung tumors, corticoid-induced cleft palate, and experimental allergic orchitis have been mapped to the central region of the H2 complex (Gas- ser et al. 1988; Oomen et al. 1991; Röpcke et al. 1990; Teuscher et al. 1990). The attribution of any of these susceptibilities to a particular gene is very difficult, since recombination in both mouse and human tends to occur at specific points (hotspots) rather than at ran- dom sites, and large genomic areas are inherited en bloc. Recently, we identified a recombinational hotspot in the class III region of the mouse telomeric to the G7a