2 GENES ENCODING STEROID 21-HYDROXYLASE ARE LOCATED NEAR THE GENES ENCODING THE 4TH COMPONENT OF COMPLEMENT IN MAN
2 GENES ENCODING STEROID 21-HYDROXYLASE ARE LOCATED NEAR THE GENES ENCODING THE 4TH COMPONENT OF COMPLEMENT IN MAN
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DOI：
10.1073/pnas.82.4.1089
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
STROMINGER, JL
中科院分区：
文献类型：
--
作者：
WHITE, PC;GROSSBERGER, D;STROMINGER, JL
编码类固醇21-羟化酶[21-OHase;类固醇21-单加氧酶;类固醇，氢供体：氧氧化还原酶（21-羟基化）; EC 1.14.99.10]（一种细胞色素P-450酶）的两个基因位于HLA主要组织相容性复合体内。先天性肾上腺皮质增生症是一种常见的遗传性皮质醇合成障碍，与某些扩展的HLA单倍型存在遗传连锁不平衡。这些单倍型包括特征性血清补体同种异型。通过使用编码补体C4部分的探针从人基因组文库中分离一系列粘粒克隆。这些克隆还与编码大部分人21-OH酶的探针杂交。限制性内切酶图谱和杂交分析表明，该菌株有2个21-OHase基因，每个基因位于其中一个C4基因的3“末端附近。与21-OHase基因5“和3”端特异性探针的杂交表明，21-OHase和C4基因都具有相同的方向。C4 A和C4 B的3“端的21-OHase基因分别携带3.2和3.7 kb的Taq I片段。这两个片段都存在于大多数个体的基因组DNA中。在HLA-A3; Bw 47; C4 A *1; C4 B *QO（null）; DR 7纯合子的严重盐耗型21-OHase缺乏症个体的DNA中，3.7-kb Taq I片段缺失，而HLA-A1;B8; C4 A * QO; C4 B *1; DR 3纯合子的正常个体不携带3.2-kb Taq I片段。21-OHase“B”基因（3.7-kb Taq I片段）有功能，但21-OHase“A”基因（3.2-kb Taq I片段）无功能。
Two genes encoding steroid 21-hydroxylase [21-OHase; steroid 21-monooxygenase; steroid, hydrogen-donor:oxygen oxidoreductase (21-hydroxylating); EC 1.14.99.10], a cytochrome P-450 enzyme, were located within the HLA major histocompatibiity complex. Congenital adrenal hyperplasia due to 21-OHase deficiency is a common inherited disorder of cortisol biosynthesis which is in genetic linkage disequilibrium with certain extended HLA haplotypes. These haplotypes include characteristic serum complement allotypes. A series of cosmid clones was isolated from a human genomic library by using a probe encoding part of complement C4. These clones also hybridized with a probe encoding most of human 21-OHase. Restriction mapping and hybridization analysis showed that there are 2 21-OHase genes, each located near the 3'' end of one of the 2 C4 genes. Hybridization with probes specific for the 5'' and 3'' ends of the 21-OHase gene showed that the 21-OHase and C4 genes all have the same orientation. The 21-OHase genes 3'' to C4A and C4B carry Taq I fragments of 3.2 and 3.7 kilobases (kb), respectively. Both of these fragments are found in genomic DNA of most individuals. In DNA from an individual with the severe, salt-wasting form of 21-OHase deficiency who was homozygous for HLA-A3;Bw47;C4A*1;C4B*QO(null);DR7, the 3.7-kb Taq I fragment is absent, whereas hormonally normal individuals homozygous for HLA-A1;B8;C4A* QO;C4B*1;DR3 do not carry the 3.2-kb Taq I fragment. The 21-OHase "B" gene (3.7-kb Taq I fragment) is functional, but the 21-OHase "A" gene (3.2-kb Taq I fragment) is not.