title: Association of a 12.5-kilobase allele of the MspI restriction fragment length polymorphism of the C6 gene in patients with total deficiency of the sixth component of complement.
abstract: The distribution of MspI restriction fragment length polymorphism (RFLP) alleles was investigated using the C6-PVX probe of the sixth component of complement (C6) and DNA from lymphocytes of 11 patients with homozygous C6 deficiency (C6Q0), 18 of their family members, 3 patients with subtotal C6 deficiency (C6SD) and 28 normal C6-sufficient controls. A biallelic polymorphism of 12.5- and 8.2-kb RFLP alleles was observed, and co-dominant inheritance of the two alleles was demonstrated in family studies. All 11 C6Q0 patients were homozygous for the 12.5-kb allele; this includes 8 unrelated propositi. The gene frequencies for both the 12.5- and 8.2-kb alleles in control subjects were 0.5, and the association of C6*Q0 with the 12.5-kb allele was found to be highly significant (p = 0.0001). Family studies in a C6Q0 family demonstrated that the MspI polymorphism may be used to trace C6*Q0 heterozygous carriers. Studies in families with C6SD, when considered with the results of C6 and C7 allotyping, showed definite co-segregation of C6*SD with the MspI 8.2-kb allele in one family and very probable co-segregation in another. All 11 South African C6Q0 subjects were homozygous for the C6Q0/MspI 12.5-kb/C7 M haplotype. Our data describe new associations of C6 deficiency genes which may assist in the future identification of the molecular defects.
authors.affiliation: Department of Clinical Science and Immunology, University of Cape Town, Groote Schuur Hospital and Medical Research Council of South Africa.
authors.forename: P C
authors.initials: PC
authors.lastname: Potter
authors.forename: C
authors.initials: C
authors.lastname: Warburton
authors.forename: R
authors.initials: R
authors.lastname: Würzner
authors.forename: A
authors.initials: A
authors.lastname: Orren
authors.forename: R
authors.initials: R
authors.lastname: Di Scipio
mesh_terms: D000483:Alleles; D001345:Autoradiography; D015139:Blotting, Southern; D003183:Complement C6 / Q000172:deficiency* / Q000235:genetics*; D003184:Complement C7 / Q000096:biosynthesis; D004247:DNA / Q000302:isolation & purification; D015342:DNA Probes; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D013019:South Africa
chemical_list: D003183:Complement C6; D003184:Complement C7; D015342:DNA Probes; D004247:DNA; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific