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跨越绵羊TRB基因座D-J-C区域的41kb基因组DNA的组织、结构与进化

Organization, structure and evolution of 41kb of genomic DNA spanning the D-J-C region of the sheep TRB locus.

作者信息

Antonacci R, Di Tommaso S, Lanave C, Cribiu E P, Ciccarese S, Massari S

机构信息

Dipartimento di Genetica e Microbiologia, Universita' degli Studi di Bari, Italy.

出版信息

Mol Immunol. 2008 Jan;45(2):493-509. doi: 10.1016/j.molimm.2007.05.023. Epub 2007 Jul 27.

DOI:10.1016/j.molimm.2007.05.023
PMID:17673294
Abstract

A genomic region of 41,045 bp encompassing the 3'-end of the sheep T cell receptor beta chain was sequenced. Extensive molecular analysis has revealed that this region retains a unique structural feature for the presence of a third D-J-C cluster, never detected in any other mammalian species examined so far. A total of 3 TRBD, 18 TRBJ and 3 substantially identical TRBC genes were identified in about 28kb. At 13kb, downstream from the last TRBC gene, in an inverted transcriptional orientation, lies a TRBV gene. Sequence comparison and phylogenetic analyses have demonstrated that the extra D-J-C cluster originated from an unequal crossing over between the two ancestral TRBC genes. Interspersed repeats spanning 22.2% of the sequence, contribute to the wider size of the sheep TRB locus with respect to the other mammalian counterparts, without modifying the general genomic architecture. The nucleotide and predicted amino acid sequences from peripheral T cells cDNA clones indicated that the genes from cluster 3 are fully implicated in the beta chain recombination machinery. Closer inspections of the transcripts have also shown that inter-cluster rearrangements and splice variants, involving the additional cluster, increase the functional diversity of the sheep beta chain repertoire.

摘要

对包含绵羊T细胞受体β链3'末端的41,045 bp基因组区域进行了测序。广泛的分子分析表明,该区域因存在第三个D-J-C簇而保留了独特的结构特征,这在迄今为止检查的任何其他哺乳动物物种中均未检测到。在约28kb中总共鉴定出3个TRBD、18个TRBJ和3个基本相同的TRBC基因。在最后一个TRBC基因下游13kb处,以反向转录方向存在一个TRBV基因。序列比较和系统发育分析表明,额外的D-J-C簇起源于两个祖先TRBC基因之间的不等交换。散布的重复序列占序列的22.2%,与其他哺乳动物对应物相比,导致绵羊TRB基因座的大小更宽,但不改变总体基因组结构。来自外周血T细胞cDNA克隆的核苷酸和预测氨基酸序列表明,来自簇3的基因完全参与β链重组机制。对转录本的进一步检查还表明,涉及额外簇的簇间重排和剪接变体增加了绵羊β链库的功能多样性。

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