DELETION OF COMPLEMENT C-4 AND STEROID 21-HYDROXYLASE GENES IN THE HLA CLASS-III REGION
DELETION OF COMPLEMENT C-4 AND STEROID 21-HYDROXYLASE GENES IN THE HLA CLASS-III REGION
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DOI：
10.1002/j.1460-2075.1985.tb03969.x
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发表时间：
1985-01-01
期刊：
影响因子：
11.4
通讯作者：
PORTER, RR
中科院分区：
文献类型：
--
作者：
CARROLL, MC;PALSDOTTIR, A;PORTER, RR
使用 C4A 或 C4B 两种形式缺陷 (QO) 个体的 DNA，绘制了人类 6 号染色体上的 HLA 区域的分子图谱，其中包括补体 C4 和类固醇 21-羟化酶基因 (21-OH)。总之，通过 Southern 分析检查了 18 个具有 C4A QO 的单倍型，其中两个具有 28-30 kb 的缺失，其中包括 C4A 和 21-OHA 基因。在六种 C4B QO 单倍型中，一种具有包含 C4B 和 21-OHA 基因的缺失。因此，一些 C4 无效等位基因是由于基因删除造成的，但该样本中的大多数等位基因并非如此。两种常见单倍型中发生缺失，表明在整个人群中，C4A 缺陷是由于大约一半的 C4A QO 单倍型缺失所致。由于 C4A 或 C4B 基因重复确实发生，因此通过从个体 C4A QO 分型的 DNA 制备粘粒克隆来检查不等交换可以解释 C4 缺失的可能性。分离出含有单个 C4B 基因的克隆基因组片段，发现其与来自携带 C4A 基因的正常个体的粘粒的同源区域相似。这表明如果发生了交叉，则发生在两个基因相同的区域。讨论了 C4A 或 C4B 缺失以及伴随的 21-OHA 基因缺失的单倍型群体中相当频繁出现的生物学意义。
Molecular maps have been prepared of the HLA region on human chromosome 6 that includes the complement C4 and steroid 21-hydroxylase genes (21-OH), using DNA of individuals deficient (QO) in either of the two forms C4A or C4B. In all, 18 haplotypes with C4A QO were examined by Southern analysis and two had deletions of 28-30 kb that included both the C4A and 21-OHA genes. Of six C4B QO haplotypes, one had a deletion that included both the C4B and 21-OHA genes. Thus, some of the C4 null alleles are due to deletion of the gene but the majority in this sample are not. Deletion occurred in two common haplotypes suggesting that in the population as a whole, C4A deficiency is due to deletion in about one-half the C4A QO haplotypes. As duplication of C4A or C4B genes does occur, the possibility that unequal cross-over could explain the C4 deletion was examined by preparing cosmid clones from the DNA of an individual typed C4A QO. A cloned genomic fragment containing the single C4B gene was isolated and found to be similar to the homologous region of a cosmid from a normal individual carrying a C4A gene. This suggests that if a crossover has occurred it is in a region where the two genes are identical. The biological significance of the rather frequent occurrence in the population of haplotypes with C4A or C4B deletion together with the accompanying deletion of the 21-OHA gene is discussed.