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人类Vκ基因座。通过黏粒克隆对扩展免疫球蛋白基因区域的表征。

The human V kappa locus. Characterization of extended immunoglobulin gene regions by cosmid cloning.

作者信息

Pohlenz H D, Straubinger B, Thiebe R, Pech M, Zimmer F J, Zachau H G

出版信息

J Mol Biol. 1987 Jan 20;193(2):241-53. doi: 10.1016/0022-2836(87)90216-6.

DOI:10.1016/0022-2836(87)90216-6
PMID:3037085
Abstract

As part of the ongoing work in our laboratory on the structural organization of the human V kappa locus we screened cosmid libraries with V kappa gene probes and obtained numerous V kappa gene-containing cosmid clones. Several genomic regions of the V kappa locus were reconstructed from overlapping cosmid inserts and were extended by one step of chromosomal walking. The regions that are called Wa, Wb, Oa, Ob and Ob' comprise about 370 kb (10(3) bases) of DNA and contain 24 V kappa genes and pseudogenes. The V kappa genes belong to the three dominant subgroups (V kappa I, V kappa II, V kappa III) and are arranged to form mixed clusters with members of the different subgroups being intermingled with each other. The distances between the genes range from 1 to 15 kb. Three genes of the Wa and Wb regions that were sequenced turned out to be pseudogenes. Terminal parts of the regions Wa and Ob that do not contain V kappa genes of one of the known subgroups may represent extended spacer regions within the V kappa locus. Wa and Wb are duplicated regions located at different positions of the locus. Region Wb was found to comprise inversely repeated sections of at least 14 kb each that contain V kappa genes oriented in opposite polarity. This finding is consistent with inversion-deletion models of V-J joining; it also shows that the V kappa locus contains not only unique and duplicated but also triplicated parts. The data on the W and O regions are discussed together with those on the L regions and on other regions established in our laboratory. Although the picture of the human V kappa locus with, to date, about 70 different non-allelic V kappa genes is still incomplete, some general features with respect to the organization of the genes and the limited duplication of genomic regions have emerged.

摘要

作为我们实验室正在进行的关于人类Vκ基因座结构组织研究工作的一部分,我们用Vκ基因探针筛选了黏粒文库,并获得了许多含Vκ基因的黏粒克隆。Vκ基因座的几个基因组区域由重叠的黏粒插入片段重建而成,并通过染色体步移进一步延伸。被称为Wa、Wb、Oa、Ob和Ob'的区域包含约370 kb(10³个碱基)的DNA,含有24个Vκ基因和假基因。Vκ基因属于三个主要亚组(VκI、VκII、VκIII),它们排列形成混合簇,不同亚组的成员相互交织。基因之间的距离在1至15 kb之间。对Wa和Wb区域的三个测序基因结果显示为假基因。Wa和Ob区域不包含已知亚组之一的Vκ基因的末端部分可能代表Vκ基因座内的延伸间隔区。Wa和Wb是位于基因座不同位置的重复区域。发现区域Wb包含至少14 kb的反向重复片段,其中含有极性相反的Vκ基因。这一发现与V-J连接的倒位-缺失模型一致;它还表明Vκ基因座不仅包含独特和重复的部分,还包含三倍重复的部分。将关于W和O区域的数据与关于L区域以及我们实验室确定的其他区域的数据一起进行了讨论。尽管目前关于人类Vκ基因座约70个不同非等位Vκ基因的情况仍不完整,但关于基因组织和基因组区域有限重复的一些一般特征已经显现出来。

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The human V kappa locus. Characterization of extended immunoglobulin gene regions by cosmid cloning.人类Vκ基因座。通过黏粒克隆对扩展免疫球蛋白基因区域的表征。
J Mol Biol. 1987 Jan 20;193(2):241-53. doi: 10.1016/0022-2836(87)90216-6.
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引用本文的文献

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Characterization of a V kappa family in Mus musculus castaneus: sequence analysis.小家鼠栗色亚种中一个Vκ家族的特征分析:序列分析
Immunogenetics. 1993;37(6):426-36. doi: 10.1007/BF00222466.
2
Characterization of a lymphoblastoid line deleted for lambda immunglobulin genes.缺失λ免疫球蛋白基因的淋巴母细胞系的特性分析
Immunogenetics. 1995;41(6):359-65. doi: 10.1007/BF00163993.
3
Organization of the T-cell antigen-receptor beta-chain locus in mice.小鼠T细胞抗原受体β链基因座的组织
Proc Natl Acad Sci U S A. 1987 Nov;84(21):7639-43. doi: 10.1073/pnas.84.21.7639.
4
Autoantibody-associated kappa light chain variable region gene expressed in chronic lymphocytic leukemia with little or no somatic mutation. Implications for etiology and immunotherapy.自身抗体相关的κ轻链可变区基因在体细胞突变很少或没有体细胞突变的慢性淋巴细胞白血病中表达。对病因学和免疫治疗的意义。
J Exp Med. 1988 Mar 1;167(3):840-52. doi: 10.1084/jem.167.3.840.
5
Physical map of the human immunoglobulin K locus and its implications for the mechanisms of VK-JK rearrangement.人类免疫球蛋白K基因座的物理图谱及其对VK-JK重排机制的影响。
Nucleic Acids Res. 1987 Dec 10;15(23):9667-76. doi: 10.1093/nar/15.23.9667.
6
Linking of the human immunoglobulin VK and JKCK regions by chromosomal walking.通过染色体步移连接人类免疫球蛋白VK和JK基因座的恒定区。
Nucleic Acids Res. 1987 Dec 10;15(23):9655-65. doi: 10.1093/nar/15.23.9655.
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Organization of the murine immunoglobulin VH complex in the inbred strains.近交系小鼠免疫球蛋白VH复合体的组织架构
EMBO J. 1987 Oct;6(10):2931-7. doi: 10.1002/j.1460-2075.1987.tb02597.x.
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N segment insertion and region-directed somatic hypermutation in a kappa gene of a t(2;8) chromosomal translocation.t(2;8)染色体易位的κ基因中的N片段插入和区域定向体细胞超突变。
Nucleic Acids Res. 1987 Jun 25;15(12):4877-88. doi: 10.1093/nar/15.12.4877.
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Three transposed elements in the intron of a human VK immunoglobulin gene.人类VK免疫球蛋白基因内含子中的三个转座元件。
Nucleic Acids Res. 1987 Nov 25;15(22):9567-75. doi: 10.1093/nar/15.22.9567.
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Genomic organization and sequences of immunoglobulin light chain genes in a primitive vertebrate suggest coevolution of immunoglobulin gene organization.一种原始脊椎动物中免疫球蛋白轻链基因的基因组组织和序列表明免疫球蛋白基因组织的共同进化。
EMBO J. 1989 Dec 1;8(12):3733-9. doi: 10.1002/j.1460-2075.1989.tb08549.x.