Genomic and cDNA analysis of the bovine TCRß gene repertoire
Genomic and cDNA analysis of the bovine TCRß gene repertoire
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牛 TCRα 基因库的基因组和 cDNA 分析
DOI：
10.1016/j.vetimm.2008.10.010
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发表时间：
2009
影响因子：
1.8
通讯作者：
Connelley T
中科院分区：
文献类型：
--
作者：
Connelley T
TCR 库的多样性是有效 aá T 细胞功能不可或缺的一部分，是通过变量 (V)、多样性（仅 D-á 链）和成分 a 和 á 链的连接 (J) 基因片段的体细胞重组产生的。为了促进牛 T 细胞反应检测技术的开发，我们对基因组和 cDNA 数据进行了广泛的分析，以表征牛 TCRá 基因库。对第三次牛基因组组装的分析表明，尽管 TCRB 基因座仍不完整，但牛的 TCRá 基因库明显大于人类或小鼠。最值得注意的是，Vá亚科的几个亚科，例如Vá1、10和13经历了广泛的复制，分别包含35、16和40名成员。这种扩展的大部分似乎是由于包含多个基因的“盒”的复制导致串联排列的重复，其中包含两个或多个亚科的成员（例如Vá18-Vá17-Vá2-Vá10）。迄今为止，已在基因组中鉴定出分布在 24 个亚科的 130 个 Vá 基因。与所检查的其他物种相比，由于 TCRB 基因座 DJC 区域的三重副本而不是重复副本，牛基因组还扩展了 Dá 和 Já 基因库。基因组组装中存在的大多数 (126/130) Vá 基因以及所有 Dá、Já 和 Cá 基因位于 4 个大支架上，其中 3 个已定位到 4 号染色体。对我们实验室完成的 cDNA 研究生成的 900 多个 TCRá 链序列进行了广泛分析，发现了 30 多个 Vá 基因在当前牛基因组组装中不存在，表明完整的基因组 Vá 库仍未定义。相反，与 cDNA 和 EST 数据的比较表明，完整的 Já 指令在基因组组装中得到了体现。 cDNA 和基因组分析相结合表明，功能性牛 TCRá 基因库由 100 多个 Vá 基因、3 个 Dá 基因和 17 个 Já 基因组成。这项工作的结果表明，牛 TCRá 基因库是迄今为止最大的特征库。某些 Vá 亚家族成员数量的急剧增加以及与人类和小鼠 TCRá 基因库的比较，提出了关于影响这一免疫学重要基因座进化的力量的有趣问题。
The diversity of the TCR repertoire that is integral to effective aá T-cell function is generated by somatic recombination of variable (V), diversity (D-á chains only) and joining (J) gene segments of the component a and á chains. To facilitate the development of techniques to examine bovine T-cell responses we undertook an extensive analysis of genomic and cDNA data to characterise the bovine TCRá gene repertoire. Analysis of the third bovine genome assembly demonstrates that although the TCRB locus is still incomplete, the TCRá gene repertoire in cattle is significantly larger than that of either humans or mice. Most notably, several of the Vá subfamilies, such as Vá1, 10 and 13 have undergone extensive duplication, containing 35, 16 and 40 members respectively. Much of this expansion appears to be due to duplication of'cassettes' containing multiple genes leading to tandemly arranged duplicates incorporating members of two or more subfamilies (eg Vá18-Vá17-Vá2-Vá10). In all, 130 Vá genes distributed over 24 subfamilies have been identified in the genome so far. Compared to other Species examined, the bovine genome also has expanded Dá and Já gene repertoires due to triplicate rather than duplicate copies of the DJC region of the TCRB locus. The majority (126/130) of the Vá genes and all of the Dá, Já and Cá genes present in the genome assembly are located of 4 large scaffolds, 3 of which have been mapped to chromosome 4. Extensive analysis of over 900 TCRá chain sequences generated from cDNA studies completed in our laboratory have identified more than 30 Vá genes that are not present in the current bovine genome assembly, indicating that the full genomic Vá repertoire remains undefined. In contrast, comparison to cDNA and EST data suggests that the full Já repertoire is represented in the genome assembly. Combination of the cDNA and genomic analyses suggest that the functional bovine TCRá gene repertoire is composed of over 100 Vá genes, 3 Dá genes and 17 Já genes. The results of this work indicate that the bovine TCRá gene repertoire is the largest yet characterised. The dramatic expansion of membership of certain Vá subfamilies and comparison to the human and murine TCRá gene repertoires raises interesting questions concerning the forces influencing the evolution of this immunologically important locus.