Qin J, Mamotte C, Cockett N E, Wetherall J D, Groth D M
School of Biomedical Sciences, Curtin University, Perth, 6845, Western Australia.
BMC Genomics. 2008 Sep 11;9:409. doi: 10.1186/1471-2164-9-409.
The central, or class III, region of the major histocompatibility complex (MHC) is an important gene rich sub-region of the MHC of mammals and contains many loci implicated in disease processes and potential productivity traits. 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. This map will facilitate association studies and provide insights into the distribution of recombination events in this chromosomal segment.
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. 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. 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. A panel of 26 single nucleotide polymorphisms (SNPs) was identified in 10 loci, covering approximately 600 kbp of the mapped region.
This report provides a physical map covering approximately 700 kbp of the class III of the sheep MHC together with a SNP panel which will facilitate disease and productivity association studies. 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.
主要组织相容性复合体（MHC）的中央区域，即III类区域，是哺乳动物MHC中一个重要的富含基因的亚区域，包含许多与疾病进程和潜在生产性状相关的基因座。作为鉴定绵羊中与生产性状相关的MHC基因座的前奏，我们利用基因组DNA的BAC和粘粒文库构建了绵羊MHC III类区域的物理图谱。该图谱将有助于关联研究，并深入了解该染色体片段中重组事件的分布情况。
在10个BAC克隆中鉴定出28个绵羊基因，这些克隆跨越了与绵羊MHC I类区域相邻的约700 kbp染色体区域，因此涵盖了绵羊MHC III类区域的大部分（如果不是全部）。确定了其中17个基因的相对位置，以及另外两组基因座内顺序未知的基因。粘粒图谱绘制允许对III类中存在的补体基因进行更详细的图谱绘制，并显示出一对重复的补体C4和CYP21基因座相对于人类存在局部倒位。在10个基因座中鉴定出一组由26个单核苷酸多态性（SNP）组成的面板，覆盖了映射区域的约600 kbp。
本报告提供了覆盖绵羊MHC III类区域约700 kbp的物理图谱以及一个SNP面板，这将有助于疾病和生产性状关联研究。一对重复的C4和CYP21基因座相对于人类存在局部倒位，以及先前描述的二核苷酸串联重复基因座（BfMs）位于SK12VL基因的一个内含子内。
