Deficiencies of human complement component C4A and C4B and heterozygosity in length variants of RP-C4-CYP21-TNX (RCCX) modules in caucasians. The load of RCCX genetic diversity on major histocompatibility complex-associated disease.
Deficiencies of human complement component C4A and C4B and heterozygosity in length variants of RP-C4-CYP21-TNX (RCCX) modules in caucasians. The load of RCCX genetic diversity on major histocompatibility complex-associated disease.
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人类补体成分C4A和C4B的缺乏以及高加索人RP-C4-CYP21-TNX（RCCX）模块的长度变体中的杂合性。 RCCX遗传多样性在主要组织相容性复合物相关疾病上的负载。
DOI：
10.1084/jem.191.12.2183
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发表时间：
2000-06-19
期刊：
影响因子：
--
通讯作者：
Yung Yu C
中科院分区：
文献类型：
--
作者：
Blanchong CA;Zhou B;Rupert KL;Chung EK;Jones KN;Sotos JF;Zipf WB;Rennebohm RM;Yung Yu C
位于主要组织相容性复合体（MHC）III类区域的补体成分C4基因在基因数量、基因大小和核苷酸多态性方面表现出异常复杂的变异模式。C4基因的重复或缺失总是与其邻近的基因丝氨酸/苏氨酸核蛋白激酶RP、类固醇21-羟化酶（CYP 21）和腱生蛋白（TNX）同时发生，它们一起形成称为RCCX模块的遗传单位。对150例正常高加索人C4 A、C4 B和RCCX模块排列进行了详细的分子遗传学分析，并与C4 A和C4 B蛋白多态性的免疫化学研究进行了相关性分析。结果表明，双模RCCX的频率为69%，而单模和三模RCCX结构分别占17.0%和14.0%。四分之三的C4基因携带内源性逆转录病毒HERV-K（C4）。C4 A和C4 B的部分缺陷，主要是由于基因缺失和C4 A蛋白的同源表达，具有31.6%的组合频率。这可能是人类基因组中基因剂量和基因大小的最常见变异。7个RCCX物理变体创建了一个伟大的单倍型和二倍体组合的剧目，杂合性频率为69.4%。这种现象促进了RCCX组分之间的遗传信息交换，这对于研究C4 A和C4 B蛋白的结构和功能差异是重要的。然而，这样的长度变异可能导致不等的染色体间交叉，导致MHC相关疾病。对22例失盐性先天性肾上腺皮质增生患者的RCCX结构的分析显示，与假基因CYP 21 A相关的长C4基因的单模块结构和两个CYP 21 A的双模块结构显著增加，这可能是由杂合RCCX长度变体之间的重组产生的。
The complement component C4 genes located in the major histocompatibility complex (MHC) class III region exhibit an unusually complex pattern of variations in gene number, gene size, and nucleotide polymorphism. Duplication or deletion of a C4 gene always concurs with its neighboring genes serine/threonine nuclear protein kinase RP, steroid 21-hydroxylase (CYP21), and tenascin (TNX), which together form a genetic unit termed the RCCX module. A detailed molecular genetic analysis of C4A and C4B and RCCX modular arrangements was correlated with immunochemical studies of C4A and C4B protein polymorphism in 150 normal Caucasians. The results show that bimodular RCCX has a frequency of 69%, whereas monomodular and trimodular RCCX structures account for 17.0 and 14.0%, respectively. Three quarters of C4 genes harbor the endogenous retrovirus HERV-K(C4). Partial deficiencies of C4A and C4B, primarily due to gene deletions and homoexpression of C4A proteins, have a combined frequency of 31.6%. This is probably the most common variation of gene dosage and gene size in human genomes. The seven RCCX physical variants create a great repertoire of haplotypes and diploid combinations, and a heterozygosity frequency of 69.4%. This phenomenon promotes the exchange of genetic information among RCCX constituents that is important in homogenizing the structural and functional diversities of C4A and C4B proteins. However, such length variants may cause unequal, interchromosomal crossovers leading to MHC-associated diseases. An analyses of the RCCX structures in 22 salt-losing, congenital adrenal hyperplasia patients revealed a significant increase in the monomodular structure with a long C4 gene linked to the pseudogene CYP21A, and bimodular structures with two CYP21A, which are likely generated by recombinations between heterozygous RCCX length variants.
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DOI：
10.1159/000463134
发表时间：
1990-03-01
期刊：
COMPLEMENT AND INFLAMMATION
影响因子：
--
作者：
MOULDS, JM;ARNETT, FC;HAMILTON, RG
通讯作者：
HAMILTON, RG
影响因子：
11.4
作者：
CARROLL, MC;PALSDOTTIR, A;PORTER, RR
通讯作者：
PORTER, RR
DOI：
10.1111/j.1445-5994.1983.tb02699.x
发表时间：
1983-01-01
期刊：
AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE
影响因子：
--
作者：
CHRISTIANSEN, FT;DAWKINS, RL;ZILKO, PJ
通讯作者：
ZILKO, PJ
影响因子：
64.8
作者：
Dodds, AW;Ren, XD;Law, SKA
通讯作者：
Law, SKA
DOI：
10.1159/000019079
发表时间：
1998-01-01
期刊：
EXPERIMENTAL AND CLINICAL IMMUNOGENETICS
影响因子：
--
作者：
Mauff, G;Luther, B;Moulds, JM
通讯作者：
Moulds, JM