THE IGA HEAVY-CHAIN GENE FAMILY IN RABBIT - CLONING AND SEQUENCE-ANALYSIS OF 13 C-ALPHA-GENES

THE IGA HEAVY-CHAIN GENE FAMILY IN RABBIT - CLONING AND SEQUENCE-ANALYSIS OF 13 C-ALPHA-GENES
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DOI:
10.1002/j.1460-2075.1989.tb08587.x
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发表时间:
1989-12-20
期刊:
影响因子:
11.4
通讯作者:
KNIGHT, KL
KNIGHT, KL
中科院分区:
生物学1区
文献类型:
--
作者:
BURNETT, RC;HANLY, WC;KNIGHT, KL

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Southern分析此前曾显示,兔子基因组包含多个基因,编码IgA重链的恒定区域。在本研究中,包含这些C.已经从粘粒和噬菌体文库中分离出基因。对克隆进行限制性内切酶图谱分析和Southern分析,鉴定出13个非等位基因。基因;11个基因聚集在单独的或重叠的克隆中。聚在一起的基因之间有8-18kb的距离,总共是C.pha。基因跨越至少160kb的DNA。Southern分析表明,一个簇中的所有基因都有相同的转录方向,13个基因中至少有12个基因的开关序列是5‘’。每个C.pha的核苷酸序列。基因被测定,似乎所有的基因都是有功能的;因此,兔可能有多达13个IgA亚型。13C.Alpha编码的蛋白质序列的比较。基因研究表明,α-链的CH2和CH3结构域高度保守,而CH1和铰链区高度多样化。来自兔形目其他物种的基因组DNA样本的Southern分析表明,所有样本都有多个C.杂交的片段。因此,很可能所有的兔儿型都有多种IgA亚型,因此具有复杂的分泌型免疫系统。
Southern analysis has previously shown that the rabbit genome contains multiple genes coding for the constant regions of IgA heavy chains. In the present study, clones containing these C.alpha. genes have been isolated from cosmid and phage libraries. Restriction mapping and Southern analysis of the clones identified 13 non-allelic C.alpha. genes; 11 of the genes were clustered in individual or over- lapping clones. The clustered genes are separated by 8-18 kb, and in total, the C.alpha. genes span a minimum of 160 kb of DNA. Southern analysis has shown that all genes within a cluster have the same transcriptional orientation, and that switch sequences are present 5'' of at least 12 of the 13 genes. The nucleotide sequence of each C.alpha. gene was determined, and it appears that all genes are functional; thus, rabbit may have as many as 13 IgA isotypes. Comparisons of the protein sequences encoded by the 13 C.alpha. genes showed that the CH2 and CH3 domains of the .alpha.-chains are highly conserved, whereas the CH1 and hinge regions are highly diverse. Southern analysis of genomic DNA samples from other species within the order Lagomorpha showed that all samples had multiple C.alpha. hybridizing fragments. Thus, it is likely that all lagomorphs have multiple IgA isotypes and hence complex secretory immune systems.