Genetic polymorphism of human complement C4 and detection of heterozygotes [8]

Z. L. Awdeh, Donald Douglas Raum, C. A. Alper

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Many components of complement exhibit inherited structural polymorphism, with at least two alleles being common in one or more of the major races of man1-9. However, definition of genetic polymorphism in human C4 has proved a difficult task. Differences between the electrophoretic patterns of C4 in EDTA plasma from different individuals were detected by Rosenfeld and co-workers10,11, but these differences could not be explained by any simple genetic model. O'Neill and co-workers12, using a system similar to that of a previous study13, interpreted the electrophoretic patterns in a completely different way from previous workers13,14, stating that there were three: F, FS and S. They also found that C4 F carried Rodgers or Rg(a + ) serologie reactivity and C4 S carried Chido or Ch(a + ) reactivity15. These 'blood group' antigens had previously been shown to be closely linked to HLA16,17. O'Neill proposed15 that C4 is genetically controlled by two closely linked loci, one for C4 F and one for C4 S, and postulated that deficiency states for one or the other locus are common but rarely occur together. The sets of haplotypes were postulated to be C4Fs° (or C4F), C4f °S (or C4S) and C4FS. In this model, the C4 F individuals are Rg(a +)Ch(a -), C4 S individuals are Rg(a -)Ch(a +) and C4 FS persons are Rg(a +)Ch(a +). The chief problem with the methods of typing, both electrophoretic and serologie, is that C4Fs° and C4f°S can usually only be detected in the homozygous state, thus severely limiting their usefulness. We have now developed a method of C4 typing that allows detection of C4Fs° and C4f°S in heterozygotes, and permits the study of genetic polymorphism of C4 in the general population. Our observations confirm and extend the two-locus genetic model of O'Neill and coworkers.

Original languageEnglish (US)
Pages (from-to)205-207
Number of pages3
JournalNature
Volume282
Issue number5735
DOIs
StatePublished - 1979
Externally publishedYes

Fingerprint

Heterozygote Detection
Complement C4
Genetic Models
Genetic Polymorphisms
Heterozygote
Blood Group Antigens
Edetic Acid
Haplotypes
Alleles
Population

ASJC Scopus subject areas

  • General

Cite this

Genetic polymorphism of human complement C4 and detection of heterozygotes [8]. / Awdeh, Z. L.; Raum, Donald Douglas; Alper, C. A.

In: Nature, Vol. 282, No. 5735, 1979, p. 205-207.

Research output: Contribution to journalArticle

Awdeh, Z. L. ; Raum, Donald Douglas ; Alper, C. A. / Genetic polymorphism of human complement C4 and detection of heterozygotes [8]. In: Nature. 1979 ; Vol. 282, No. 5735. pp. 205-207.
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abstract = "Many components of complement exhibit inherited structural polymorphism, with at least two alleles being common in one or more of the major races of man1-9. However, definition of genetic polymorphism in human C4 has proved a difficult task. Differences between the electrophoretic patterns of C4 in EDTA plasma from different individuals were detected by Rosenfeld and co-workers10,11, but these differences could not be explained by any simple genetic model. O'Neill and co-workers12, using a system similar to that of a previous study13, interpreted the electrophoretic patterns in a completely different way from previous workers13,14, stating that there were three: F, FS and S. They also found that C4 F carried Rodgers or Rg(a + ) serologie reactivity and C4 S carried Chido or Ch(a + ) reactivity15. These 'blood group' antigens had previously been shown to be closely linked to HLA16,17. O'Neill proposed15 that C4 is genetically controlled by two closely linked loci, one for C4 F and one for C4 S, and postulated that deficiency states for one or the other locus are common but rarely occur together. The sets of haplotypes were postulated to be C4Fs° (or C4F), C4f °S (or C4S) and C4FS. In this model, the C4 F individuals are Rg(a +)Ch(a -), C4 S individuals are Rg(a -)Ch(a +) and C4 FS persons are Rg(a +)Ch(a +). The chief problem with the methods of typing, both electrophoretic and serologie, is that C4Fs° and C4f°S can usually only be detected in the homozygous state, thus severely limiting their usefulness. We have now developed a method of C4 typing that allows detection of C4Fs° and C4f°S in heterozygotes, and permits the study of genetic polymorphism of C4 in the general population. Our observations confirm and extend the two-locus genetic model of O'Neill and coworkers.",
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