Albertella M R, Jones H, Thomson W, Olavesen M G, Campbell R D
MRC Immunochemistry Unit, Department of Biochemistry, Oxford University, South Parks Road, Oxford, OX1 3QU, United Kingdom.
Genomics. 1996 Sep 1;36(2):240-51. doi: 10.1006/geno.1996.0459.
A wide range of autoimmune and other diseases are known to be associated with the major histocompatibility complex. Many of these diseases are linked to the genes encoding the polymorphic histocompatibility antigens in the class I and class II regions, but some appear to be more strongly associated with genes in the central 1100-kb class III region, making it important to characterize this region fully for the presence of novel genes. An approximately 220-kb segment of DNA in the class III region separating the Hsp70 (HSPA1L) and BAT1 (D6S8IE) genes, which was previously known to contain 14 genes, has been analyzed for the presence of additional genes. Genomic DNA fragments spanning the gaps between the known genes were used as probes to isolate cDNAs corresponding to five new genes within this region. Evidence from Northern blot analysis and exon trapping experiments that suggested the presence of at least two more new genes was also obtained. Partial cDNA and complete exonic genomic sequencing of one of the new genes has identified it as the casein kinase II beta subunit (CSNK2B). Two of the other novel genes lie within a region syntenic to that implicated in susceptibility to experimental allergic orchitis in the mouse, an autoimmune disease of the testis, and represent additional candidates for the Orch-1 locus associated with this disease. In addition, characterization of the 13-kb intergenic gap separating the RD (D6545) and G11 (D6S60E) genes has revealed the presence of a gene encoding a 1246-amino-acid polypeptide that shows significant sequence similarity to the yeast anti-viral Ski2p gene product.
已知多种自身免疫性疾病和其他疾病与主要组织相容性复合体相关。其中许多疾病与编码I类和II类区域多态性组织相容性抗原的基因有关,但有些疾病似乎与中央1100 kb III类区域的基因关联更为紧密,因此全面表征该区域以寻找新基因显得尤为重要。对III类区域中位于热休克蛋白70(HSPA1L)基因和BAT1(D6S8IE)基因之间的一段约220 kb的DNA片段进行了分析,该片段先前已知包含14个基因,此次分析其是否存在其他基因。跨越已知基因之间间隙的基因组DNA片段被用作探针,以分离该区域内对应于五个新基因的cDNA。通过Northern印迹分析和外显子捕获实验也获得了证据,表明至少还存在另外两个新基因。对其中一个新基因的部分cDNA和完整外显子基因组测序已确定其为酪蛋白激酶IIβ亚基(CSNK2B)。其他两个新基因位于与小鼠实验性过敏性睾丸炎(一种睾丸自身免疫性疾病)易感性相关区域的同线区域内,是与该疾病相关的Orch-1位点的额外候选基因。此外,对分隔RD(D6545)基因和G11(D6S60E)基因的13 kb基因间间隙的表征揭示了一个编码1246个氨基酸多肽的基因的存在,该多肽与酵母抗病毒Ski2p基因产物具有显著的序列相似性。