title: Polymorphism of human complement component C6: an amino acid substitution (Glu/Ala) within the second thrombospondin repeat differentiates between the two common allotypes C6 A and C6 B.
abstract: Component C6 of the human complement system exhibits a genetic polymorphism in all populations tested so far. Using isoelectric focusing two common allotypes, C6 A ('acidic') and C6 B ('basic') and a number of rare variants have been described. A comparison of the two published cDNA sequences of C6 suggests a polymorphism in codon 98. Using polymerase chain reaction (PCR) we amplified a segment of the human C6 gene encompassing the presumably polymorphic codon. According to the restriction fragment patterns obtained after DdeI digestion of the PCR product, three genotypes were distinguished. The polymorphism is caused by a nucleotide substitution (C-->A) in the second position of codon 98; allele 1 (GCG) codes for Ala, allele 2 (GAG) for Glu. Sequencing of PCR products confirmed the mutation. For 46 unrelated individuals genotyped by this PCR-based method we also determined C6 protein phenotype. Three phenotypes were observed (C6 A, C6 AB, C6 B). There was an absolute concordance between C6 protein typing and DNA typing. We thus conclude that the C6 A allotype is characterized by a Glu and the C6 B allotype by an Ala residue in position 98 of the C6 polypeptide chain.
authors.affiliation: Institute of Human Genetics, University of Bonn, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Dewald
authors.forename: M M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: S
authors.initials: S
authors.lastname: Cichon
mesh_terms: D000409:Alanine; D000595:Amino Acid Sequence; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003001:Cloning, Molecular; D003183:Complement C6 / Q000235:genetics* / Q000302:isolation & purification; D005838:Genotype; D005971:Glutamates; D018698:Glutamic Acid; D006801:Humans; D007525:Isoelectric Focusing; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011994:Recombinant Proteins / Q000302:isolation & purification; D012091:Repetitive Sequences, Nucleic Acid; D019699:Thrombospondins
chemical_list: D015815:Cell Adhesion Molecules; D003183:Complement C6; D005971:Glutamates; D009838:Oligodeoxyribonucleotides; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins; D019699:Thrombospondins; D018698:Glutamic Acid; D000409:Alanine