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牛λ轻链基因座的组织与基因组复杂性

Organization and genomic complexity of bovine lambda-light chain gene locus.

作者信息

Pasman Yfke, Saini Surinder S, Smith Elspeth, Kaushik Azad K

机构信息

Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G 2W1.

出版信息

Vet Immunol Immunopathol. 2010 Jun 15;135(3-4):306-13. doi: 10.1016/j.vetimm.2009.12.012. Epub 2010 Feb 2.

Abstract

Complete characterization and physical mapping of bovine lambda (lambda) light chain locus, spanning 412kbp, on chromosome 17, has revealed twenty-five V(lambda) genes, seventeen being functional, organized in three sub-clusters 23.7kbp 5' of the J(lambda)-C(lambda) units. Three V(lambda) sub-clusters are separated by two large introns of 126.8 and 138.3kbp. The predominantly expressed V(lambda)1 genes are present in the two 5' sub-clusters, while J(lambda)-proximal V(lambda) sub-cluster comprises rarely expressed V(lambda)2 and V(lambda)3 genes. The preferential expression of V(lambda)1 genes in the bovine immunoglobulin repertoire is influenced by the composition of recombination signal sequences (RSS). Of the J(lambda)-C(lambda) cluster, it is mainly J(lambda)3-C(lambda)3 unit that is expressed in reading frame 2, though J(lambda)2 and J(lambda)3 have identical RSS. The predominant expression of J(lambda)3-C(lambda)3 genes over J(lambda)2-C(lambda)2 is likely due to endogenous counter selection for J(lambda)2 encoded CDR3 and framework 4 regions. Differences in the genomic complexity of V(lambda) genes in Hereford and Holstein cattle are due to polymorphism at the lambda-light chain gene locus. Despite more potential germline encoded combinatorial diversity, restricted V(lambda)1-J(lambda)3-C(lambda)3 recombinations encode the most lambda-light chain repertoire in cattle.

摘要

对位于17号染色体上跨度为412kbp的牛λ轻链基因座进行的完整表征和物理图谱绘制,揭示了25个V(λ)基因,其中17个具有功能,它们在J(λ)-C(λ)单元5'端的23.7kbp处组织成三个亚簇。三个V(λ)亚簇被两个分别为126.8kbp和138.3kbp的大内含子隔开。主要表达的V(λ)1基因存在于两个5'端亚簇中,而靠近J(λ)的V(λ)亚簇包含很少表达的V(λ)2和V(λ)3基因。牛免疫球蛋白库中V(λ)1基因的优先表达受重组信号序列(RSS)组成的影响。在J(λ)-C(λ)簇中,主要是J(λ)3-C(λ)3单元在阅读框2中表达,尽管J(λ)2和J(λ)3具有相同的RSS。J(λ)3-C(λ)3基因比J(λ)2-C(λ)2基因的优势表达可能是由于对J(λ)2编码的互补决定区3(CDR3)和构架区4的内源性反向选择。赫里福德牛和荷斯坦牛V(λ)基因的基因组复杂性差异是由于λ轻链基因座的多态性。尽管有更多潜在的种系编码组合多样性,但受限的V(λ)1-J(λ)3-C(λ)3重组编码了牛中最多的λ轻链库。

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