Shin E K, Matsuda F, Nagaoka H, Fukita Y, Imai T, Yokoyama K, Soeda E, Honjo T
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
EMBO J. 1991 Dec;10(12):3641-5. doi: 10.1002/j.1460-2075.1991.tb04930.x.
We have constructed the physical map of the 3' region of the human immunoglobulin heavy chain variable region (VH) genes. DNA segments extending to 200 kb upstream of the JH segment were isolated in two YAC clones. Five VH segments were identified in this region in the 5' to 3' order, V(II-5), V(IV-4), V(I-3), V(I-2), and V(VI-1) segments which were all structurally normal and orientated in the same direction as the JH segments. From DNA of a different cell line we have isolated a cosmid contig containing the same DNA region which has extraordinary polymorphism. The YAC and cosmid DNAs were called haplotypes A and B, respectively. Haplotype B contained an additional VH-I segment (V(I-4.1b)) between the V(II-5) and V(IV-4) segments. V(I-4.1b) segment is almost identical to a previously published VH sequence encoding a rheumatoid factor. Another VH segment in the B haplotype (V(I-3b)) corresponding to the V(I-3) segment also showed 99.7% nucleotide sequence homology with an anti-DNA autoantibody VH sequence. However, none of the VH sequences in haplotype A showed such strong homology with autoantibody VH sequences. The results suggest that VH haplotypes may have linkage with autoantibody production.
我们构建了人类免疫球蛋白重链可变区（VH）基因3'区域的物理图谱。在两个酵母人工染色体（YAC）克隆中分离出了延伸至JH片段上游200 kb的DNA片段。在该区域按5'至3'顺序鉴定出五个VH片段，即V（II - 5）、V（IV - 4）、V（I - 3）、V（I - 2）和V（VI - 1）片段，它们在结构上均正常，且与JH片段方向相同。我们从另一种细胞系的DNA中分离出了一个包含相同DNA区域的黏粒重叠群，该区域具有非凡的多态性。YAC和黏粒DNA分别被称为单倍型A和B。单倍型B在V（II - 5）和V（IV - 4）片段之间包含一个额外的VH - I片段（V（I - 4.1b））。V（I - 4.1b）片段与先前发表的编码类风湿因子的VH序列几乎相同。B单倍型中的另一个VH片段（V（I - 3b））与V（I - 3）片段对应，它与抗DNA自身抗体VH序列也显示出99.7%的核苷酸序列同源性。然而，单倍型A中的VH序列均未与自身抗体VH序列显示出如此强的同源性。结果表明，VH单倍型可能与自身抗体产生存在连锁关系。
