New microsatellite size variants as markers for a cross-over hotspot in the C4-H-2D region

Abstract

Various autoimmune diseases have been linked to the MHC (M611er 1983; Todd et al. 1988). In the mouse, MHC-associated susceptibility has been observed for lupus nephritis (Jacob and McDevitt 1988), autoimmune diabetes in the nonobese diabetic mouse (NOD) (Prochazka et al. 1987), and experimental allergic orchitis (Teuscher et al. 1990). Also, other traits have been mapped to the central part of the MHC, such as the susceptibility to cleft palate (Gasser et al. 1988); susceptibility to chemically induced lung tumors (Oomen et al. 1991); susceptibility to hormonally induced mammary tumors (R6pcke et al. 1990); the "hybrid resistance" phenomenon (Rembecki et al. 1988); and the immune response to TNP-Ficoll (Hillstrom Shapiro et al. 1985). Identification of the responsible genes was hampered by the limited knowledge of the organization of this part of the MHC and the lack of sufficient polymorphic markers. The recent characterization of a number of genes in this part of the chromosome sheds light on the genomic organization. However, the number of polymorphic markers remains rather low. Therefore, the generation of such markers in the class III region of the mouse is of interest for the mapping and identification of genes involved in MHC-associated diseases or traits. We cloned a + 100-kb-long segment derived from the C4-H-2D interval of the central region of the mouse MHC of the 14-2 b haplotype (Shock et al. 1993). Our contig of overlapping cosmid clones contains murine counterparts of the genes described in the homologous region in human (Sargent et al. 1989; Spies et al. 1989; Milner and Campbell 1990; Olavesen et al. 1993), namely, G9, Hsp70.1, Hsp70.3, Hsc7Ot, G7b, G7a (Bat-6), and part of the G7 gene (Shock et al. 1993). Analysis of many intra-H-2 recombinants with the recombination site in the C4-H-2D region had indicated the presence of a recombinational hot