Inherited structural polymorphism of the fourth component of human complement.
Zuheir L. Awdeh,Chester A. Alper +1 more
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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.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.read more
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Book ChapterDOI
Systemic lupus erythematosus, complement deficiency, and apoptosis.
TL;DR: It was found that inherited complement deficiency is strongly associated with the development of SLE, and downstream events following complement activation could explain theDevelopment of autoantibodies to complement and to erythrocyte CR1 consumption.
Journal ArticleDOI
Gene Copy-Number Variation and Associated Polymorphisms of Complement Component C4 in Human Systemic Lupus Erythematosus (SLE): Low Copy Number Is a Risk Factor for and High Copy Number Is a Protective Factor against SLE Susceptibility in European Americans
Yan Yang,Erwin K. Chung,Yee Ling Wu,Stephanie L. Savelli,Haikady N. Nagaraja,Bi Zhou,Maddie Hebert,Karla N. Jones,Yaoling Shu,Kathryn J. Kitzmiller,Carol A. Blanchong,Kim L. McBride,Gloria C. Higgins,Robert M. Rennebohm,Robert R. Rice,Kevin V. Hackshaw,Robert Roubey,Jennifer M. Grossman,Betty P. Tsao,Daniel J. Birmingham,Brad H. Rovin,Lee A. Hebert,C. Yung Yu +22 more
TL;DR: Family-based association tests suggested that a specific haplotype with a single short C4B in tight linkage disequilibrium with the -308A allele of TNFA was more likely to be transmitted to patients with SLE.
Journal ArticleDOI
Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility.
A. H. L. Fielder,Mark Walport,J. R. Batchelor,R. I. Rynes,Carol M. Black,I. A. Dodi,Grv Hughes +6 more
TL;DR: The known association of systemic lupus erythematosus with uncommon inherited and acquired deficiencies of complement components suggests, however, that the presence of null alleles for C4A and C4B, as well as C2, found in most of the patients, is relevant to their genetic susceptibility to this disease.
Journal ArticleDOI
Genetic prediction of nonresponse to hepatitis B vaccine.
Chester A. Alper,Margot S. Kruskall,Deborah Marcus-Bagley,Donald E. Craven,Aubrey J. Katz,Stuart J. Brink,Jules L. Dienstag,Zuheir L. Awdeh,Edmond J. Yunis +8 more
TL;DR: It is concluded that the usual response to hepatitis B surface antigen is due to the presence of a dominant immune-response gene in the MHC and that a low response isdue to the absence of such a gene and the presence on both chromosomes of MHC haplotypes that indicate such a response.
Journal ArticleDOI
The structural basis of the multiple forms of human complement component C4
TL;DR: Comparison with partial sequences of a second C4A allele and a C4B allele has led to the tentative identification of some class differences in nucleotide sequences between C3A and C3B and of allelic differences between C4 a and B alleles in this highly polymorphic system.
References
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Journal ArticleDOI
Genetic polymorphism in human glycine-rich beta-glycoprotein.
TL;DR: Electrophoretic studies of fragments from defined types of GBG suggested that GBG cleavage induced by complement or properdin activation in serum occurred through this C moiety, since two variants were detectable in one fragment and two were found in the other fragment.
Journal ArticleDOI
Isoelectric Focusing in Polyacrylamide Gel and its Application to Immunoglobulins
TL;DR: In this form the technique has been successfully applied to studies on the heterogeneity of myoglobins, cytochrome c6, lactoperoxidase7 and a number of other proteins (see review by Haglund8).
Journal ArticleDOI
Two HLA-linked loci controlling the fourth component of human complement
TL;DR: Family studies showed that this polymorphism of C4 did not segregate with HLA histocompatibility genes in a fashion governed by two codominant alleles at a single genetic locus, in agreement with the hypothesis that two different genetic loci control the electrophoretic patterns of C 4.
Journal ArticleDOI
Inherited structural polymorphism in human C2: evidence for genetic linkage between C2 and Bf.
TL;DR: Structural variation in the second component of human complement was identified in about 4% of serum samples from random unrelated individuals of all the major races and suggestive evidence for close linkage between C2 and Bf was obtained.
Journal ArticleDOI
α -Globin gene organisation in blacks precludes the severe form of α -thalassaemia
Andrée M. Dozy,Yuet Wai Kan,Stephen H. Embury,Stephen H. Embury,William C. Mentzer,William C. Mentzer,Wei Wang,Wei Wang,Bertram H. Lubin,J. R. Davis,H. M. Koenig +10 more
TL;DR: Characterised α-thalassaemia in people of African origin is characterised using the restriction endonuclease mapping technique of Southern to delineate the nature of the deletion of the α-globin genes.
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