Wilton A N, Johnstone R W, McKenzie I F, Purcell D F
School of Biological Sciences, Macquarie University, NSW, Australia.
Immunogenetics. 1992;36(2):79-85. doi: 10.1007/BF00215283.
Human CD46 (membrane cofactor protein) is a cell surface glycoprotein with cofactor activity for the factor I mediated cleavage of components C3b and C4b. Using a CD46 cDNA clone, three restriction enzymes give simple two allele restriction fragment length polymorphisms (RFLPs) in samples of over 300 Caucasians. For Pvu II, P1 with a 16.5 kilobase (kb) fragment and P2 with 14.8 kb + 1.9 kb fragments have frequencies of .40 and .60. For Hin dIII, H1 with a 4.3 kb fragment and H2 with a 2.3 kb fragment have similar frequencies. For Bgl. II, B1 with a 10 kb fragment and B2 with 8.3 kb + 1.8 kb fragments have frequencies of 0.08 and 0.92. There is strong linkage disequilibrium between these polymorphic sites. Designating haplotypes by Hin dIII, Pvu II, Bgl II alleles, there are two common haplotypes P2, H2, B2 and P1, H1, B2, expected at frequencies of .6 and .32, one less common haplotype P1, H1, B1 expected at a frequency .08. The two major protein isoforms of CD46, as detected on peripheral blood lymphocytes by western blot, of Mr 66,000 (alpha) and 56,000 (beta) are determined by differential splicing in production of the mRNA. A strong association between protein isoform and RFLP haplotypes in 30 unrelated subjects suggests that the splicing preference site is in linkage disequilibrium with the RFLPs. The results are consistent with haplotypes P2, H2, B2 and P1, H1, B1 producing predominantly alpha; P1, H1, B2 producing predominantly beta in about 72% of cases and alpha in 28% of cases.
人类CD46（膜辅因子蛋白）是一种细胞表面糖蛋白，对I因子介导的C3b和C4b成分裂解具有辅因子活性。利用一个CD46 cDNA克隆，三种限制酶在300多名高加索人的样本中产生了简单的双等位基因限制性片段长度多态性（RFLP）。对于Pvu II，带有16.5千碱基（kb）片段的P1和带有14.8 kb + 1.9 kb片段的P2的频率分别为0.40和0.60。对于Hin dIII，带有4.3 kb片段的H1和带有2.3 kb片段的H2频率相似。对于Bgl. II，带有10 kb片段的B1和带有8.3 kb + 1.8 kb片段的B2的频率分别为0.08和0.92。这些多态性位点之间存在很强的连锁不平衡。用Hin dIII、Pvu II、Bgl II等位基因指定单倍型，有两种常见单倍型P2、H2、B2和P1、H1、B2，预期频率分别为0.6和0.32，一种不太常见的单倍型P1、H1、B1预期频率为0.08。通过蛋白质免疫印迹在外周血淋巴细胞上检测到的CD46的两种主要蛋白质异构体，分子量分别为66,000（α）和56,000（β），是由mRNA产生过程中的差异剪接决定的。在30名无关个体中，蛋白质异构体与RFLP单倍型之间存在很强的关联，这表明剪接偏好位点与RFLP处于连锁不平衡状态。结果表明，单倍型P2、H2、B2和P1、H1、B1主要产生α；P1、H1、B2在约72%的情况下主要产生β，在28%的情况下产生α。
