Alper C A, Awdeh Z L, Yunis E J
Center for Blood Research, Dana-Farber Cancer Institute, Boston, Mass.
Complement Inflamm. 1989;6(1):8-18. doi: 10.1159/000463067.
The region on the short arm of the sixth human chromosome encoding class I and class II histocompatibility antigens involved in immune recognition also encodes a group of molecules unrelated to HLA termed class III which includes C2, C4, and factor B. The four genes encoding the complement proteins occupy about 120 kb of genomic DNA between HLA-B and HLA-DR and are closer to HLA-DR. The four genes are inherited as a single unit, without observed crossover, called a complotype, designated by its BF, C2, C4A, and C4B alleles. There are about fifteen complotypes with frequencies of 0.01 or higher on normal caucasian chromosomes. Analysis of linkage disequilibrium between HLA-B, HLA-DR alleles, and complotypes reveals that about 30% of normal caucasian chromosomes consist of fixed sets called extended or fixed haplotypes. There are over a dozen such extended haplotypes defined by their HLA-B, DR and complotype alleles. They appear to contribute most of the previously described linkage disequilibrium between HLA-A/HLA-B and HLA-B/HLA-DR allelic pairs as well as most of the known HLA marker-disease associations. It is postulated that extended haplotypes consist of fixed DNA over at least the 10(6) base pairs of the HLA-B-DR interval, and independent examples in apparently unrelated individuals are thus identical or nearly identical over this interval. A practical consequence of this concept is the possible prediction of successful tissue transplantation donor-recipient pairs.
人类第六条染色体短臂上编码参与免疫识别的I类和II类组织相容性抗原的区域，还编码了一组与HLA无关的分子，称为III类分子，其中包括C2、C4和B因子。编码补体蛋白的四个基因在HLA - B和HLA - DR之间占据约120 kb的基因组DNA，且更靠近HLA - DR。这四个基因作为一个单一单元遗传，未观察到交叉现象，称为补体单倍型，由其BF、C2、C4A和C4B等位基因指定。在正常白种人的染色体上，约有十五种补体单倍型，其频率为0.01或更高。对HLA - B、HLA - DR等位基因和补体单倍型之间连锁不平衡的分析表明，约30%的正常白种人染色体由称为扩展或固定单倍型的固定组合组成。有超过一打这样的扩展单倍型，由它们的HLA - B、DR和补体单倍型等位基因定义。它们似乎构成了先前描述的HLA - A/HLA - B和HLA - B/HLA - DR等位基因对之间的大部分连锁不平衡，以及大部分已知的HLA标记与疾病的关联。据推测，扩展单倍型至少在HLA - B - DR区间的10(6)个碱基对上由固定的DNA组成，因此在明显不相关个体中的独立实例在这个区间上是相同或几乎相同的。这一概念的一个实际后果是可能预测成功的组织移植供体 - 受体对。
