The molecular genetics of components of complement.
The molecular genetics of components of complement.
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DOI：
10.1016/s0065-2776(08)60007-3
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发表时间：
1986-01-01
影响因子：
--
通讯作者：
Porter, R R
中科院分区：
文献类型：
--
作者：
Campbell, R D;Carroll, M C;Porter, R R
在建立连锁和在染色体上分配大约9种补体成分的基因方面取得了迅速的进展。在MHC中，C2、因子B和两个C4或C4相关基因已经在人和小鼠中被详细地定位。编码细胞色素P-450 21-羟化酶的基因已被证明是重复的，并且紧邻两个C4基因的3'，尽管它似乎在功能上和结构上与补体成分无关。因此，六个基因已经被定位到这个区域，其中特定的单倍型与对许多疾病的易感性增加有关，其中一些是自身免疫性的。因子B的完整基因结构已经在人类中得到解决，并且在C2和C4基因方面正在取得快速进展。这些基因多态性的结构基础正在建立。在C4中，多态性异常复杂，具有不同数量的基因座，并且可能在人类中存在50多种同种异型。还发现了人类中某些C4同种异型生物学活性的巨大差异的结构基础。除了MHC中的基因外，还发现了编码C4 bp、CR 1和H因子的基因之间的连锁。值得注意的是，这些蛋白质与C2和因子B之间存在序列同源性，这可能与结合结构相似的蛋白质C3 B和C4 B中的一种或另一种的能力有关。小鼠和人C3和C4的完整cDNA序列提供了许多关于这些蛋白质的许多翻译后修饰的信息。已获得C3基因的部分结构，并显示C3、C4、C5、α 2-巨球蛋白和妊娠带蛋白之间的同源性。尽管补体成分的分子遗传学的详细信息量正在迅速积累，但似乎有一个合理的前景，即连锁和同源性将把数据分类为可理解的形式。
Rapid progress has been made in establishing linkages and in chromosome allocation of the genes of some 9 complement components. In the MHC, C2, Factor B, and two C4 or C4 related genes have been placed in some detail in both man and mouse. The gene coding for the cytochrome P-450 21-hydroxylase has been shown to be duplicated and immediately 3' to the two C4 genes, though it appears to be functionally and structurally unrelated to the complement components. Thus six genes have been mapped to this region where particular haplotypes are associated with increased susceptibility to a number of diseases, some of which are autoimmune in character. The complete gene structure of Factor B has been solved in man and rapid progress is being made with the C2 and C4 genes. The structural basis of the polymorphisms of these genes is being established. In C4, the polymorphism is exceptionally complex with varying numbers of loci and probably more than 50 allotypes occurring in man. A structural basis has also been found for the big differences in the biological activity of some of the C4 allotypes in man. Apart from the genes in the MHC, linkage has been found between the genes coding for C4bp, CR1, and Factor H. Remarkably there are sequence homologies between these proteins and C2 and Factor B, probably related to the ability to bind to one or other of the structurally similar proteins C3b and C4b. The complete cDNA sequences of C3 and C4 in mouse and man have given much information on the many posttranslational modifications of these proteins. A partial structure has been obtained for the C3 gene and the homology shown between C3, C4, C5, alpha 2-macroglobulin, and pregnancy zone protein. Although the amount of detailed information in the molecular genetics of complement components is accumulating rapidly, there appears to be a reasonable prospect that linkages and homologies will classify the data into a comprehensible form.