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Strong associations between RFLP and protein polymorphisms for CD46.

Wilton AN, Johnstone RW, McKenzie IF, Purcell DF

  • Journal Immunogenetics

  • Published 24 Jul 1992

  • Volume 36

  • ISSUE 2

  • Pagination 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.