In humans, the class III spans approximately 800 kbp with a gene density of one per 11.4 kbp. Loci within the class III are often highly conserved and in general terms evolved prior to the class I and II loci. Many other genes not directly associated with immune responses have also been mapped to this region. The MHC class III is very gene dense and contains genes of many types including the complement genes C4, C2 and CFB, the Hsp70 genes and genes in the TNF cytokine family. The class I and class II regions contain genes encoding glycoproteins expressed predominantly by cells of the immune system and which act as receptors for peptides derived from self and non-self antigens. In some species the class I and class II regions are further subdivided to include an extended class I and extended class II region respectively. Mammalian MHC typically comprise three regions – class I and class II regions usually separated by a central region which is sometimes referred to as the class III region. The human MHC is the most gene-dense region of the human genome. The major histocompatibility complex (MHC) consists of a cluster of genes within a genomic region which encodes molecules responsible for the expression of adaptive and innate immune responses in vertebrates. The presence of a local inversion (relative to humans) of one pair of the duplicated C4 and CYP21 loci and a previously described dinucleotide tandem repeat locus (BfMs) has been located within an intron of the SK12VL gene. This report provides a physical map covering ≈700 kbp of the class III of the sheep MHC together with a SNP panel which will facilitate disease and productivity association studies. A panel of 26 single nucleotide polymorphisms (SNPs) was identified in 10 loci, covering ≈600 kbp of the mapped region. Cosmid mapping permitted a more detailed mapping of the complement genes present in the class III and showed a local inversion (relative to humans) of one pair of the duplicated complement C4 and CYP21 loci. The relative positions of 17 of these genes was established as well as two additional groups of genes for which the intragroup order was not known.
Twenty eight sheep genes were identified in 10 BAC clones which spanned approximately 700 kbp of a chromosomal region adjacent to the class I region of the sheep MHC and which therefore covers most, if not all, of the class III of the sheep MHC. This map will facilitate association studies and provide insights into the distribution of recombination events in this chromosomal segment.
As a prelude to identifying MHC loci associated with productivity traits in sheep, we have used BAC and cosmid libraries of genomic DNA to generate a physical map of the sheep MHC class III region.
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