Genomic structure of the human MHC class I MICB gene
Genomic structure of the human MHC class I MICB gene
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DOI：
10.1007/s002510050184
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发表时间：
1996-01-01
期刊：
影响因子：
3.2
通讯作者：
Inoko, H
中科院分区：
文献类型：
--
作者：
Bahram, S;Shiina, T;Inoko, H
人类主要组织相容性复合体(MHC)除了包含众所周知的人类白细胞抗原I类基因外，还包含高度分化的MHC I类链相关(MIC)基因家族(巴赫拉姆等人。1994年；巴赫拉姆和间谍组织1996a)。在该家族中，密切相关的MICA和MICB基因分别编码1382和2376个碱基对(BP)的转录本(巴赫拉姆等人。1994年；巴赫拉姆和间谍组织1996b)。MICA分子由一个11722个碱基的异常大的基因编码，位于人类白细胞抗原-B基因座的着丝粒约40千碱基(Kb)(巴拉姆等人)。1996年)。在此，我们报道了MICB基因的12930个核苷酸序列，位于MICA的着丝粒附近约70kb。该序列是从从粘粒TY2A9获得的枪枪亚克隆DNA片段获得的，粘粒TY2A9是覆盖该HLA亚区的粘粒重叠群的成员，并从从B-LCL，BOLETH分离的YAC克隆产生(H.Inoko，未发表的数据)。MICB的基因组结构与MICA相似(巴赫拉姆等人)。1996；图1)，并且有别于其他I类基因(Malissen等人)。1982年)。特别是，一个7352bp的大内含子(MICA中为6840bp)分隔了前两个外显子，而一个1338bp的6个外显子(MICA中为302bp)同时编码细胞质尾部和39个未翻译的(39UT)序列。因此，过量的39UT序列是MICA和MICB转录本之间约1kb长度差异的原因(巴赫拉姆等人。1994年，巴赫拉姆和间谍组织1996b)。正如预期的那样，在MICA和MICB的编码序列中观察到的高度相似性延伸到了这两个基因。实际上，将MICB的单个外显子和内含子与它们在MICA中的对应相比较提供了以下序列相似性程度(基于采用MegAlign程序Lasergene Navigator(DNAStar，Madison，WI)的Clustal方法的默认参数的比对：外显子1的80%、内含子1的52%、外显子2的91%、内含子2的86%、外显子3的90%、内含子3的87%、外显子4的98%、内含子4的97%、外显子5的73%、内含子5的83%，将MICB基因组序列与先前发表的cDNA序列进行比较，发现有4个非同义核苷酸替换：121：GAA(E)？GGA(G)，243：aAG(K)？-GAG(E)(均在α1内)，第411：Gat(D)？AAT(N)(α2)和904GTG(V)？GCG(A)(TM)。有趣的是，这些位置都不与先前定义的MICA多态残基匹配(Fodil等人。1996年)。MICA和MICB基因核苷酸组成的可用性增加了我们对人类MHC这一特定片段的了解，这一片段与许多风湿性疾病的易感性特别相关。
The human major histocompatibility complex (MHC) contains, in addition to the well known HLA class I genes, the highly divergent MHC class I chain-related (MIC) gene family (Bahram et al. 1994; Bahram and Spies 1996a). Within this family, the closely related MICA and MICB genes encode transcripts of 1382 and 2376 base pairs (bp), respectively (Bahram et al. 1994; Bahram and Spies 1996b). The MICA molecule is encoded by an unusually large gene of 11722 bp, located about 40 kilobases (kb) centromeric to the HLA-B locus (Bahram et al. 1996). Here we report the 12930 bp nucleotide sequence of the MICB gene, located approximately 70 kb centromeric to MICA. The sequence was obtained from shot-gun subcloned DNA fragments derived from the cosmid TY2A9, a member of a cosmid contig covering this HLA sub-region and generated from a YAC clone isolated from the B-LCL, BOLETH (H. Inoko, unpublished data). The genomic organization of MICB is similar to that of MICA (Bahram et al. 1996; Fig. 1) and distinct from other class I genes (Malissen et al. 1982). In particular, a large intron of 7352 bp (6840 bp in MICA) separates the first two exons, and a single six exon of 1338 bp (302 bp in MICA) encodes both the cytoplasmic tail and the 39 untranslated (39UT) sequence. Excess 39UT sequence is therefore responsible for the approximately 1 kb length difference between the MICA and MICB transcripts (Bahram et al. 1994, Bahram and Spies 1996b). As expected, the high degree of similarity observed within the coding sequences of MICA and MICB extends throughout both genes. Indeed, comparing individual exons and introns of MICB with their counterparts in MICA provides the following degrees of sequence similarity (based on an alignment employing the default parameters of the Clustal method of the MegAlign program, Lasergene Navigator (DNASTAR, Madison, WI): 80% for exon 1, 52% for intron 1, 91% for exon 2, 86% for intron 2, 90% for exon 3, 87% for intron 3, 98% for exon 4, 97% for intron 4, 73% for exon 5, 83% for intron 5, and finally 82% for exon 6. Comparing the MICB genomic sequence with the previously published cDNA sequence reveals four non-synonymous nucleotide substitutions [numbers correspond to nucleotide positions reported in Bahram and Spies (1996 b)]: 121: GAA (E)? GGA (G), 243: AAG (K)?-GAG (E)(both within α1), 411: GAT (D)? AAT (N)(α2) and 904 GTG (V)? GCG (A)(TM). Interestingly, none of these positions match the previously defined MICA polymorphic residues (Fodil et al. 1996). Availability of the nucleotide composition of the MICA and MICB genes adds to our knowledge of this particular segment of the human MHC, which is specifically associated with susceptibility to a number of rheumatic disorders.