Hereditary C5 Deficiency in Man: Genetic Linkage Studies

Abstract

Abstract Genetic linkage studies were performed on the only reported kindred with genetic deficiency of the fifth component of complement (C5). Thirty family members in four generations were studied for C5 deficiency and 32 genetic marker systems. Of these marker loci, 13 were informative in this pedigree. Most importantly, C5 deficiency was excluded (lod score < -2.0) from linkage with the major histocompatibility locus (HLA) for a recombination frequency of <15% (in females). Other marker systems excluded from linkage with C5 deficiency included the ceruloplasmin and Duffy loci at a recombination frequency of <15%, and the erythrocyte glyoxalase, MN, and Lewis loci at a recombination frequency of <5%. The most positive lod score (1.07, ϑ=0.05) was for linkage between C5 and haptoglobin, but this score does not reach statistical significance. Thus, among the genes for complement components which can be mapped because of deficiency states or polymorphic gene products, C5 joins C1r, C3 and C6 in not being closely linked to HLA. In contrast, close HLA linkage has been demonstrated for C2, C4, properdin factor B and, in one of two families, C8.