Inherited Structural Polymorphism of the Fourth Component of Human Complement

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1980 Jun 1

PMID 6932037

Citations 158

Authors

Z L Awdeh

C A Alper

Affiliations

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Abstract

Human fourth component of complement (C4) was found to be highly polymorphic by agarose gel electrophoresis of neuraminidase-treated plasma. The system allows clear-cut separation of the products of the two C4 genetic loci, C4A (acidic or Rodgers) and C4B (basic or Chido). There are at least six structural variants and a deletion allele at the C4A locus and two structural variants and a deletion allele at the C4B locus. Close linkage with no crossovers was found between the two C4 loci, allowing the definition of C4AB haplotypes, and between C4 haplotypes and the C2 and BF loci of the human histocompatibility complex. Nine C4 haplotypes, each with a frequency of 0.005 or more in Caucasians, were found. These studies provide direct evidence for two distinct but closely linked genetic loci for human C4 in the major histocompatibility complex on the short arm of chromosome 6.

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References

Awdeh Z, Williamson A, Askonas B . Isoelectric focusing in polyacrylamide gel and its application to immunoglobulins. Nature. 1968; 219(5149):66-7. DOI: 10.1038/219066a0. View

Rosenfeld S, Ruddy S, Austen K . Structural polymorphism of the fourth component of human complement. J Clin Invest. 1969; 48(12):2283-92. PMC: 297485. DOI: 10.1172/JCI106194. View

Passmore H, Shreffler D . A sex-limited serum protein variant in the mouse: inheritance and association with the H-2 region. Biochem Genet. 1970; 4(3):351-65. DOI: 10.1007/BF00485752. View

Alper C, BOENISCH T, Watson L . Genetic polymorphism in human glycine-rich beta-glycoprotein. J Exp Med. 1972; 135(1):68-80. PMC: 2139116. DOI: 10.1084/jem.135.1.68. View

Middleton J, CROOKSTON M, Falk J, Robson E, Cook P, Batchelor J . Linkage of Chido and HL-A. Tissue Antigens. 1974; 4(4):366-73. DOI: 10.1111/j.1399-0039.1974.tb00262.x. View

Longster G, Giles C . A new antibody specificity, anti-Rga, reacting with a red cell and serum antigen. Vox Sang. 1976; 30(3):175-80. DOI: 10.1111/j.1423-0410.1976.tb02810.x. View

Giles C, Gedde-Dahl Jr T, Robson E, Thorsby E, Olaisen B, Arnason A . Rga (Rodgers) and the HLA region: linkage and associations. Tissue Antigens. 1976; 8(2):143-9. View

Alper C . Inherited structural polymorphism in human C2: evidence for genetic linkage between C2 and Bf. J Exp Med. 1976; 144(4):1111-5. PMC: 2190428. DOI: 10.1084/jem.144.4.1111. View

Teisberg P, Akesson I, Olaisen B, Gedde-Dahl Jr T, Thorsby E . Genetic polymorphism of C4 in man and localisation of a structural C4 locus to the HLA gene complex of chromosome 6. Nature. 1976; 264(5583):253-4. DOI: 10.1038/264253a0. View

10.

Ochs H, Rosenfeld S, Thomas E, GIBLETT E, Alper C, DuPont B . Linkage between the gene (or genes) controlling synthesis of the fourth component of complement and the major histocompatibility complex. N Engl J Med. 1977; 296(9):470-5. DOI: 10.1056/NEJM197703032960902. View

11.

Bitter-Suermann D, Kronke M, Brade V, HADDING U . Inherited polymorphism of guinea pig factor B and C4: evidence for genetic linkage between the C4 and Bf loci. J Immunol. 1977; 118(5):1822-6. View

12.

Teisberg P, Olaisen B, Jonassen R, Gedde-Dahl Jr T, Thorsby E . The genetic polymorphism of the fourth component of human complement: methodological aspects and a presentation of linkage and association data relevant to its localization in the HLA region. J Exp Med. 1977; 146(5):1380-9. PMC: 2180975. DOI: 10.1084/jem.146.5.1380. View

13.

Mauff G, Bender K, Fischer B . Genetic polymorphism of the fourth component of human complement. Vox Sang. 1978; 34(5):296-301. DOI: 10.1111/j.1423-0410.1978.tb02485.x. View

14.

ONEILL G, Yang S, Tegoli J, Berger R, DuPont B . Chido and Rodgers blood groups are distinct antigenic components of human complement C4. Nature. 1978; 273(5664):668-70. DOI: 10.1038/273668a0. View

15.

Roos M, Atkinson J, Shreffler D . Molecular characterization of the Ss and Slp (C4) proteins of the mouse H-2 complex: subunit composition, chain size polymorphism, and an intracellular (PRO-Ss) precursor. J Immunol. 1978; 121(3):1106-15. View

16.

Ferreira A, NUSSENZWEIG V, Gigli I . Structural and functional differences between the H-2 controlled Ss and Slp proteins. J Exp Med. 1978; 148(5):1186-97. PMC: 2185059. DOI: 10.1084/jem.148.5.1186. View

17.

ONEILL G, Yang S, DuPont B . Two HLA-linked loci controlling the fourth component of human complement. Proc Natl Acad Sci U S A. 1978; 75(10):5165-9. PMC: 336285. DOI: 10.1073/pnas.75.10.5165. View

18.

Raum D, Alper C, Stein R, GABBAY K . Genetic marker for insulin-dependent diabetes mellitus. Lancet. 1979; 1(8128):1208-10. DOI: 10.1016/s0140-6736(79)91895-6. View

19.

Olaisen B, Teisberg P, Nordhagen R, Michaelsen T, Gedde-Dahl Jr T . Human complement C4 locus is duplicated on some chromosomes. Nature. 1979; 279(5715):736-7. DOI: 10.1038/279736a0. View

20.

ONEILL G, DuPont B . Serum C4 levels, Chido, Rodgers, and allotypes of C4 component of complement. Transplant Proc. 1979; 11(1):1102-6. View