Shiina Takashi, Briles W Elwood, Goto Ronald M, Hosomichi Kazuyoshi, Yanagiya Kazuyo, Shimizu Sayoko, Inoko Hidetoshi, Miller Marcia M
Division of Basic Medical Science and Molecular Medicine, Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan.
J Immunol. 2007 Jun 1;178(11):7162-72. doi: 10.4049/jimmunol.178.11.7162.
MHC haplotypes have a remarkable influence on whether tumors form following infection of chickens with oncogenic Marek's disease herpesvirus. Although resistance to tumor formation has been mapped to a subregion of the chicken MHC-B region, the gene or genes responsible have not been identified. A full gene map of the subregion has been lacking. We have expanded the MHC-B region gene map beyond the 92-kb core previously reported for another haplotype revealing the presence of 46 genes within 242 kb in the Red Jungle Fowl haplotype. Even though MHC-B is structured differently, many of the newly revealed genes are related to loci typical of the MHC in other species. Other MHC-B loci are homologs of genes found within MHC paralogous regions (regions thought to be derived from ancient duplications of a primordial immune defense complex where genes have undergone differential silencing over evolutionary time) on other chromosomes. Still others are similar to genes that define the NK complex in mammals. Many of the newly mapped genes display allelic variability and fall within the MHC-B subregion previously shown to affect the formation of Marek's disease tumors and hence are candidates for genes conferring resistance.
MHC单倍型对鸡感染致癌性马立克氏病疱疹病毒后是否形成肿瘤具有显著影响。尽管对肿瘤形成的抗性已定位到鸡MHC - B区域的一个子区域,但相关的一个或多个基因尚未确定。该子区域完整的基因图谱一直缺失。我们已将MHC - B区域基因图谱扩展至超过先前针对另一个单倍型报道的92 kb核心区域,揭示了原鸡单倍型中242 kb范围内存在46个基因。尽管MHC - B的结构有所不同,但许多新发现的基因与其他物种MHC中的典型基因座相关。其他MHC - B基因座是在其他染色体上MHC旁系同源区域(被认为源自原始免疫防御复合体的古代重复区域,其中基因在进化过程中经历了差异沉默)内发现的基因的同源物。还有一些与定义哺乳动物NK复合体的基因相似。许多新定位的基因表现出等位基因变异性,且位于先前显示会影响马立克氏病肿瘤形成的MHC - B子区域内,因此是赋予抗性的候选基因。