title: Complement component C6 and C7 haplotypes associated with deficiencies of C6.
abstract: Both complete C6-deficiency (C6*Q0) and subtotal C6-deficiency (C6*SD) have been described as simple recessive traits and C6*SD has been described in combination with subtotal deficiency of the C7 coded at an adjacent locus. The trace of C6 protein found in both C6*SD traits is phenotypically indistinguishable, being smaller than normal C6 and having different isoelectric properties. A defect has been found in the C6 gene which plausibly explains the C6*SD phenotype, and this defect is also common to both C6*SD traits. We present data from seven DNA markers of the C6 and C7 genes which show that although at least four haplotypes are associated with C6*Q0, most South African C6*Q0 patients carry a common defective haplotype. The most common haplotype associated with C6*Q0 has been observed only once among unaffected haplotypes of relatives. In one family, the cases of C6*SD share a complete haplotype with both cases of combined deficiency and are probably heterozygous for this condition and complete deficiency of C6. In another family, the C6*SD is on a slightly different haplotype and C7 is normally expressed. Thus, the C6 defect is not sufficient on its own to explain the C7 deficiency in the combined deficient haplotype. The haplotype associated with the combined deficiency is found not only in normal control subjects, but also in one case of complete C6 deficiency. In this case the molecular defect seen in combined or C6*SD cases is absent.
authors.affiliation: Molecular Immunopathology Unit, MRC Centre, Cambridge, U.K.
authors.forename: B A
authors.initials: BA
authors.lastname: Fernie
authors.forename: A
authors.initials: A
authors.lastname: Orren
authors.forename: R
authors.initials: R
authors.lastname: Würzner
authors.forename: A M
authors.initials: AM
authors.lastname: Jones
authors.forename: P C
authors.initials: PC
authors.lastname: Potter
authors.forename: P J
authors.initials: PJ
authors.lastname: Lachmann
authors.forename: M J
authors.initials: MJ
authors.lastname: Hobart
mesh_terms: D000483:Alleles; D003183:Complement C6 / Q000172:deficiency* / Q000235:genetics*; D003184:Complement C7 / Q000172:deficiency / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D003183:Complement C6; D003184:Complement C7; D005819:Genetic Markers