Screening for polymorphism in the tyrosine-sulfated region of human C4

• Published in: Human molecular genetics 1993-10, Vol.2 (10), p.1733-1734
• Main Authors: Mejia, José, Lahsaini, Khalid, Tongio, Marie-Marthe, Hauptmann, Georges
• Format: Article
• Language: English
• Subjects: Base Sequence; Biological and medical sciences; Chromosomes, Human, Pair 6; Classical genetics, quantitative genetics, hybrids; Complement C4 - genetics; complement component C4; Fundamental and applied biological sciences. Psychology; Genes; Genetics of eukaryotes. Biological and molecular evolution; haplotypes; Haplotypes - genetics; Human; Humans; Major Histocompatibility Complex - genetics; man; Molecular Sequence Data; Polymerase Chain Reaction; polymorphism; Polymorphism, Genetic; screening; sulfation; tyrosine; Tyrosine - analogs & derivatives
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/2.10.1733

The human Major Histocompatibility Complex (MHC) is located in the short arm of chromosome 6. MHC class I (HLA-A, B, and C) and class II (HLA-DP, DQ, and DR) genes encode highly polymorphic surface glycoproteins involved in the induction and regulation of immune response. C4, the fourth component of complement, is encoded in the class III region of the MHC. C4 is also highly polymorphic, as more than 30 allotypes of C4 have been described. C4 is unique among complement proteins in that three tyrosine-O-sulfation sites are clustered near the C-terminal end of its alpha chain. Sulfation of tyrosine residues has been recognized as a post-translational modification of many plasma proteins and other secretory proteins. Experiments with sulfation inhibitors showed that in vitro hemolytic activity of nonsulfated C4 was markedly decreased, probably from impaired interaction with C1s, the complement protease that physiologically activates C4. It is intriguing that a C4 cDNA clone has been described which lacks the codons for an Asp-Tyr-Glu tripeptide containing one of the three consecutive sulfation sites. It has been proposed that this may reflect additional genetic polymorphism of the C4 molecule. The association between C4 deficiency and auto-immune diseases prompted us to explore this possibility. We have used the polymerase chain reaction (PCR) to screen 56 MHC "extended" haplotypes (HLA plus class III polymorphic markers) of Caucasians, on the basis of the expected 9-bp length difference in the PCR products.