Spies T, Blanck G, Bresnahan M, Sands J, Strominger J L
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138.
Science. 1989 Jan 13;243(4888):214-7. doi: 10.1126/science.2911734.
A 435-kilobase (kb) DNA segment, which is centromeric to HLA-B in the human major histocompatibility complex, was isolated by chromosome walking with overlapping cosmids. Within the cloned region, the genes for the tumor necrosis factors (TNFs) alpha and beta and HLA-B were 210 kb apart. The human homolog of a mouse gene, B144, was located next to TNF alpha. Moreover, the presence of additional genes was suggested by a large cluster of CpG islands. With cosmid probes, several distinct transcripts were detected in RNA samples from a variety of cell lines. Altogether, five novel genes were identified by isolation of corresponding complementary DNA clones. These "HLA-B-associated transcripts" (BATs) were mapped to different locations within a 160-kb region that includes the genes for TNF alpha and TNF beta. The presence of the genes for BAT1 and BAT5 in the vicinity of HLA-B again raises the question of which gene in this region determines susceptibility to ankylosing spondylitis.
通过使用重叠黏粒进行染色体步移,分离出了一段435千碱基对(kb)的DNA片段,该片段位于人类主要组织相容性复合体中HLA - B的着丝粒侧。在克隆区域内,肿瘤坏死因子(TNF)α和β的基因与HLA - B相距210 kb。小鼠基因B144的人类同源物位于TNFα旁边。此外,一大簇CpG岛提示存在其他基因。使用黏粒探针,在来自多种细胞系的RNA样本中检测到了几种不同的转录本。通过分离相应的互补DNA克隆,总共鉴定出了五个新基因。这些“与HLA - B相关的转录本”(BATs)被定位到一个160 kb区域内的不同位置,该区域包括TNFα和TNFβ的基因。BAT1和BAT5基因在HLA - B附近的存在再次提出了该区域中哪个基因决定强直性脊柱炎易感性的问题。