Internal Duplications of DH, JH, and C Region Genes Create an Unusual IgH Gene Locus in Cattle
Internal Duplications of DH, JH, and C Region Genes Create an Unusual IgH Gene Locus in Cattle
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DH、JH 和 C 区基因的内部重复在牛中产生了不寻常的 IgH 基因位点
DOI：
10.4049/jimmunol.1600158
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发表时间：
2016-05-15
影响因子：
4.4
通讯作者：
Zhao，Yaofeng
中科院分区：
文献类型：
--
作者：
Ma，Li;Qin，Tong;Zhao，Yaofeng
多年来，人们一直怀疑牛具有两个功能性IgH基因位点，分别位于普通牛常染色体（BTA）21和BTA 11上。在本研究中，基于荧光原位杂交和额外的实验，我们发现，所有功能的牛IgH基因都位于BTA 21，只有一个截短的μ CH 2外显子存在于BTA 11。通过对从Hostein牛细菌人工染色体文库中筛选的7个细菌人工染色体克隆进行测序，我们产生了678-kb的连续基因组序列，其覆盖牛IGHV、IGHD、IGHJ和IGHC基因，其组织为IGHVn-IGHDn-IGHJn-IGHM 1-（IGHDP-IGHV 3-IGHDn）3-IGHJn-IGHM 2-IGHD-IGHG 3-IGHG 1-IGHG 2-IGHE-IGHA。虽然两个功能性IGHM基因IGHM 1和IGHM 2都可以通过独立的VDJ重组表达，但IGHM 2也可以通过类别转换重组表达。可能是因为更多的IGHD片段可以参与IGHM 2的表达，IGHM 2基因显示在整个不同发育阶段的大多数组织中占主导地位。根据编码序列的长度和同一性，在该基因座中鉴定的23个IGHD片段可分为9个亚组（称为IGHD 1至IGHD 9）。IGHD 9基因除两个成员（14 bp）外，其余功能片段均大于30 bp，其中IGHD 8基因最长（149 bp）。这些非常长的生殖系IGHD区段在牛中产生异常大的H链CDR 3长度变异性中起关键作用。
It has been suspected for many years that cattle possess two functional IgH gene loci, located on Bos taurus autosome (BTA) 21 and BTA11, respectively. In this study, based on fluorescence in situ hybridization and additional experiments, we showed that all functional bovine IgH genes were located on BTA21, and only a truncated μCH2 exon was present on BTA11. By sequencing of seven bacterial artificial chromosome clones screened from a Hostein cow bacterial artificial chromosome library, we generated a 678-kb continuous genomic sequence covering the bovine IGHV, IGHD, IGHJ, and IGHC genes, which are organized as IGHVn-IGHDn-IGHJn-IGHM1-(IGHDP-IGHV3-IGHDn)3-IGHJn-IGHM2-IGHD-IGHG3-IGHG1-IGHG2-IGHE-IGHA. Although both of two functional IGHM genes, IGHM1 and IGHM2, can be expressed via independent VDJ recombinations, the IGHM2 can also be expressed through class switch recombination. Likely because more IGHD segments can be involved in the expression of IGHM2, the IGHM2 gene was shown to be dominantly expressed in most tissues throughout different developmental stages. Based on the length and identity of the coding sequence, the 23 IGHD segments identified in the locus could be divided into nine subgroups (termed IGHD1 to IGHD9). Except two members of IGHD9 (14 nt in size), all other functional IGHD segments are longer than 30 nt, with the IGHD8 gene (149 bp) to be the longest. These remarkably long germline IGHD segments play a pivotal role in generating the exceptionally great H chain CDR 3 length variability in cattle.