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The Complete Nucleotide Sequence of the Human Immunoglobulin Heavy Chain Variable Region Locus

人免疫球蛋白重链可变区基因座的完整核苷酸序列

基本信息

批准号：
09670335
负责人：
TASHIRO Kei
金额：
$ 1.79万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

The complete nucleotide sequence of the 957-kb DNA of the human immunoglobulin heavy chain variable (V_H) region locus was determined and 43 novel V_H segments were identified. The region contains 123 V_H segments classifiable into seven different families, of which 79 are pseudogenes. Of the 44 V_H segments with an open reading Frame, 39 are expressed as heavy chain proteins and 1 as mRNA, while the remaining 4 are not found in immunoglobulin cDNAs. Combinatorial diversity of V_H region was calculated to be -6,000. Conservation of the promoter and recombination signal sequences was observed to be higher in functional V_H segments than in pseudogenes. Phylogenetic analysis of 114 V_H segments clearly showed clustering of the V_H segments of each family. However, an independent branch in the tree contained a single V_H, V4-44.1P, sharing similar levels of homology to human V_H families and to those of other vertebrates. Comparison between different copies of homologous units that appear repeatedly across the locus clearly demonstrates that dynamic DNA reorganization of the locus took place at least eight times between 133 and 10 million years ago. One nonimmunoglobulin gene of unknown function was identified in the intergenic region.

测定了人免疫球蛋白重链可变位点（V_H） 957 kb DNA的全核苷酸序列，鉴定出43个新的V_H片段。该区域包含123个V_H片段，可分为7个不同的科，其中79个为假基因。在44个具有开放阅读框的V_H片段中，39个表达为重链蛋白，1个表达为mRNA，其余4个不存在于免疫球蛋白cdna中。V_H区域的组合多样性计算为- 6000。在功能性V_H片段中，启动子和重组信号序列的保守性高于假基因。对114个V_H片段的系统发育分析表明，各科V_H片段具有明显的聚类性。然而，该树中的一个独立分支包含一个V_H， V4-44.1P，与人类V_H家族和其他脊椎动物的V_H家族具有相似的同源性。对重复出现在基因座上的同源单位的不同拷贝的比较清楚地表明，在1.33亿至1000万年前，基因座的动态DNA重组至少发生了8次。在基因间区发现了一个功能未知的非免疫球蛋白基因。