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. 1976 Nov;58(5):1240–1248. doi: 10.1172/JCI108578

The chromosomal order of genes controlling the major histocompatibility complex, properdin factor B, and deficiency of the second component of complement.

D Raum, D Glass, C B Carpenter, C A Alper, P H Schur
PMCID: PMC333293  PMID: 993342

Abstract

The relationship of the genes coding for HLA to those coding for properdin Factor B allotypes and for deficiency of the second component of complement (C2) was studied in families of patients with connective tissue disorders. Patients were selected because they were heterozygous or homozygous for C2 deficiency. 12 families with 15 matings informative for C2 deficiency were found. Of 57 informative meioses, two crossovers were noted between the C2 deficiency gene and the HLA-B gene, with a recombinant fraction of 0.035. A lod score of 13 was calculated for linkage between C2 deficiency and HLA-B at a maximum likelihood value of the recombinant fraction of 0.04. 18 families with 21 informative matings for both properdin Factor B allotype and HLA-B were found. Of 72 informative meioses, three recombinants were found, giving a recombinant fraction of 0.042. A lod score of 16 between HLA-B and Factor B allotypes was calculated at a maximum likelihood value of the recombinant fraction of 0.04. A crossover was shown to have occurred between genes for Factor B and HLA-D, in which HLA-D segregared with HLA-A and B. These studies suggest that the genes for Factor B and C2 deficiency are located outside those for HLA, that the order of genese is HLA-A, -B, -D, Factor B allotype, C2 deficiency, that the genes coding for C2 deficiency and Factor B allotypes are approximately 3--5 centimorgans from the HLA-A and HLA-B loci, and that the apparent lack of recombinants between the Factor B gene and C2 deficiency gene suggests that these two genes lie in close proximity to one another.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen F. H., Jr Linkage of HL-A and GBG. Vox Sang. 1974;27(4):382–384. doi: 10.1111/j.1423-0410.1974.tb02433.x. [DOI] [PubMed] [Google Scholar]
  2. Alper C. A., Boenisch T., Watson L. Genetic polymorphism in human glycine-rich beta-glycoprotein. J Exp Med. 1972 Jan;135(1):68–80. doi: 10.1084/jem.135.1.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Alpert E., Monroe M., Schur P. H. A method for increasing the sensitivity of radial-immunodiffusion assay. Lancet. 1970 May 23;1(7656):1120–1120. doi: 10.1016/s0140-6736(70)92796-0. [DOI] [PubMed] [Google Scholar]
  4. Borsos T., Rapp H. J. Immune hemolysis: a simplified method for the preparation of EAC'4 with guinea pig or with human complement. J Immunol. 1967 Aug;99(2):263–268. [PubMed] [Google Scholar]
  5. Curman B., Ostberg L., Sandberg L., Malmheden-Eriksson I., Stålenheim G., Rask L., Peterson P. A. H-2 linked Ss protein is C4 component of complement. Nature. 1975 Nov 20;258(5532):243–245. doi: 10.1038/258243a0. [DOI] [PubMed] [Google Scholar]
  6. Day N. K., L'Esperance R., Good R. A., Michael A. F., Hansen J. A., Dupont B., Jersild C. Hereditary C2 deficiency: Genetic studies and association with the HL-A system. J Exp Med. 1975 Jun 1;141(6):1464–1469. doi: 10.1084/jem.141.6.1464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dorf M. E., Maurer P. H., Merryman F., Benacerraf B. Inclusion group systems and cis-trans effects in responses controlled by the two complementing Ir-GLphi genes. J Exp Med. 1976 Apr 1;143(4):889–896. doi: 10.1084/jem.143.4.889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Démant P., Capková J., Hinzová E., Vorácová B. The role of the histocompatibility-2-linked Ss-Slp region in the control of mouse complement. Proc Natl Acad Sci U S A. 1973 Mar;70(3):863–864. doi: 10.1073/pnas.70.3.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fearon D. T., Ruddy S., Schur P. H., McCabe W. R. Activation of the properdin pathway of complement in patients with gram-negative of bacteremia. N Engl J Med. 1975 May 1;292(18):937–940. doi: 10.1056/NEJM197505012921802. [DOI] [PubMed] [Google Scholar]
  10. Ferreira A., Nussenweig V. Control of C3 levels in mice during ontogeny by a gene in the central region of the H-2 complex. Nature. 1976 Apr 15;260(5552):613–615. doi: 10.1038/260613a0. [DOI] [PubMed] [Google Scholar]
  11. Fu S. M., Kunkel H. G., Brusman H. P., Allen F. H., Jr, Fotino M. Evidence for linkage between HL-A histocompatibility genes and those involved in the synthesis of the second component of complement. J Exp Med. 1974 Oct 1;140(4):1108–1111. doi: 10.1084/jem.140.4.1108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fu S. M., Stern R., Kunkel H. G., Dupont B., Hansen J. A., Day N. K., Good R. A., Jersild C., Fotino M. Mixed lymphocyte culture determinants and C2 deficiency: LD-7a associated with C2 deficiency in four families. J Exp Med. 1975 Aug 1;142(2):495–506. doi: 10.1084/jem.142.2.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gibson D. J., Glass D., Carpenter C. B., Schur P. H. Hereditary C2 deficiency: diagnosis and HLA gene complex associations. J Immunol. 1976 Apr;116(4):1065–1070. [PubMed] [Google Scholar]
  14. Glass D., Raum D., Gibson D., Stillman J. S., Schur P. H. Inherited deficiency of the second component of complement. Rheumatic disease associations. J Clin Invest. 1976 Oct;58(4):853–861. doi: 10.1172/JCI108538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hartzman R. J., Segall M., Bach M. L., Bach F. H. Histocompatibility matching. VI. Miniaturization of the mixed leukocyte culture test: a preliminary report. Transplantation. 1971 Mar;11(3):268–273. doi: 10.1097/00007890-197103000-00005. [DOI] [PubMed] [Google Scholar]
  16. Hauptmann G., Sasportes M., Tongio M. M., Mayer S., Dausset J. The localization of the Bf locus within the MHS region on chromosome no. 6. Tissue Antigens. 1976 Jan;7(1):52–54. doi: 10.1111/j.1399-0039.1976.tb01029.x. [DOI] [PubMed] [Google Scholar]
  17. Jongsma A., van Someren H., Westerveld A., Hagemeijer A., Pearson P. Localization of genes on human chromosomes by studies of human-Chinese hamster somatic cell hybrids. Assignment of PGM3 to chromosome C6 and regional mapping of the PGD, PGM1 and pep-C genes on chromosome A1. Humangenetik. 1973 Dec 10;20(3):195–202. doi: 10.1007/BF00385730. [DOI] [PubMed] [Google Scholar]
  18. Keuning J. J., van den Tweel J. G., Gabb B. W., Termijtelen A., Goulmy E., Blokland E., Elferink B. G., van Rood J. J. An estimation of the recombination fraction between the MLC locus and the FOUR locus. Tissue Antigens. 1975 Sep;6(3):107–115. doi: 10.1111/j.1399-0039.1975.tb00623.x. [DOI] [PubMed] [Google Scholar]
  19. Lachmann P. J., Grennan D., Martin A., Demant P. Identification of Ss protein as murine C4. Nature. 1975 Nov 20;258(5532):242–243. doi: 10.1038/258242a0. [DOI] [PubMed] [Google Scholar]
  20. Lamm L. U., Friedrich U., Petersen C. B., Jorgensen J., Nielsen J., Therkelsen A. J., Kissmeyer-Nielsen F. Assignment of the major histocompatibility complex to chromosome No. 6 in a family with a pericentric inversion. Hum Hered. 1974;24(3):273–284. doi: 10.1159/000152660. [DOI] [PubMed] [Google Scholar]
  21. Lamm L. U., Jorgensen F., Kissmeyer-Nielsen F. Bf maps between the HLA--A and D loci. Tissue Antigens. 1976 Feb;7(2):122–124. doi: 10.1111/j.1399-0039.1976.tb01041.x. [DOI] [PubMed] [Google Scholar]
  22. Lamm L. U., Kissmeyer-Nielsen F., Svejgaard A., Petersen G. B., Thorsby E., Mayr W., Högman C. On the orientation of the HL-A region and the PGM3 locus in the chromosome. Tissue Antigens. 1972;2(3):205–214. doi: 10.1111/j.1399-0039.1972.tb00137.x. [DOI] [PubMed] [Google Scholar]
  23. Lamm L. U., Thorsen I. L., Petersen G. B., Jorgensen J., Henningsen K., Bech B., Kissmeyer-Nielsen F. Data on the HL-A linkage group. Ann Hum Genet. 1975 May;38(4):383–390. doi: 10.1111/j.1469-1809.1975.tb00628.x. [DOI] [PubMed] [Google Scholar]
  24. MORTON N. E. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318. [PMC free article] [PubMed] [Google Scholar]
  25. Meo T., Krasteff T., Shreffler D. C. Immunochemical characterization of murine H-2 controlled Ss (serum substance) protein through identification of its human homologue as the fourth component of complement. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4536–4540. doi: 10.1073/pnas.72.11.4536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mittal K. K., Mickey M. R., Singal D. P., Terasaki P. I. Serotyping for homotransplantation. 18. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation. 1968 Nov;6(8):913–927. doi: 10.1097/00007890-196811000-00006. [DOI] [PubMed] [Google Scholar]
  27. Rittner C., Grosse-Wilde H., Netzel B., Scholz S., Lorenz H., Albert E. D. Linkage group HL-A-MLC-BF (properdin factor B). The site of the Bf locus at the immunogenetic linkage group on chromosome 6. Humangenetik. 1975;27(3):173–183. doi: 10.1007/BF00278344. [DOI] [PubMed] [Google Scholar]
  28. Rubinstein P., Suciu-Foca N., Nicholson J. F., Fotino M., Molinaro A., Harisiadis L., Hardy M. A., Reemtsma K., Allen F. H., Jr The HLA system in the families of patients with juvenile diabetes mellitus. J Exp Med. 1976 May 1;143(5):1277–1282. doi: 10.1084/jem.143.5.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ruddy S., Klemperer M. R., Rosen F. S., Austen K. F., Kumate J. Hereditary deficiency of the second component of complement (C2) in man: correlation of C2 haemolytic activity with immunochemical measurements of C2 protein. Immunology. 1970 Jun;18(6):943–954. [PMC free article] [PubMed] [Google Scholar]
  30. Schur P. H., Connelly A., Jones T. C. Phylogeny of complement components in non-human primates. J Immunol. 1975 Jan;114(1 Pt 2):270–273. [PubMed] [Google Scholar]
  31. Sturt E. The use of lod scores for the determination of the order of loci on a chromosome. Ann Hum Genet. 1975 Oct;39(2):255–260. doi: 10.1111/j.1469-1809.1975.tb00127.x. [DOI] [PubMed] [Google Scholar]
  32. Tartof K. D. Redundant genes. Annu Rev Genet. 1975;9:355–385. doi: 10.1146/annurev.ge.09.120175.002035. [DOI] [PubMed] [Google Scholar]
  33. Teisberg P., Olaisen B., Gedde-Dahl T., Jr, Thorsby E. On the localization of the Gb locus within the MHS region of chromosome No. 6. Tissue Antigens. 1975 May;5(4):257–261. doi: 10.1111/j.1399-0039.1975.tb01472.x. [DOI] [PubMed] [Google Scholar]
  34. Weitkamp L. R., Van Rood J. J., Thorsby E., Bias W., Fotino M., Lawler S. D., Dausset J., Mayr W. R., Bodmer J., Ward F. E. The relation of parental sex and age to recombination in the HL-A system. Hum Hered. 1973;23(3):197–205. doi: 10.1159/000152574. [DOI] [PubMed] [Google Scholar]
  35. Wolski K. P., Schmid F. R., Mittal K. K. Genetic linkage between the HL-A system and a deficit of the second component (C2) of complement in four generations of a family. Tissue Antigens. 1976 Jan;7(1):35–38. doi: 10.1111/j.1399-0039.1976.tb01026.x. [DOI] [PubMed] [Google Scholar]
  36. Ziegler J. B., Alper C. A., Balner H. Properdin factor B and histocompatibility loci linked in the rhesus monkey. Nature. 1975 Apr 17;254(5501):609–611. doi: 10.1038/254609a0. [DOI] [PubMed] [Google Scholar]

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