, Volume 40, Issue 6, pp 425–436

The dichotomous size variation of human complement C4 genes is mediated by a novel family of endogenous retroviruses, which also establishes species-specific genomic patterns among Old World primates

  • Andrew W. Dangel
  • Anna R. Mendoza
  • C. D. Menachery
  • Bradley J. Baker
  • Charles M. Daniel
  • Michael C. Carroll
  • Lai-Chu Wu
  • C. Yung Yu
Original Paper


The human complement C4 genes in the HLA exhibit an unusual, dichotomous size polymorphism and a four-gene, modular variation involving novel gene RP, complement C4, steroid 21-hydroxylase (CYP21), and tenascin-like Gene X (RCCX). The C4 gene size dichotomy is mediated by an endogenous retrovirus, HERV-K(C4). Nearly identical sequences for this retrotransposon are present precisely at the same location in the long C4 genes from the tandem RCCX Module I and Module II. Specific nucleotide substitutions between the long and short C4 genes have been identified and used for diagnosis. Southern blot analyses revealed that HERV-K(C4) is present at more than 30 locations in the human genome, exhibits variations in the population, and its analogs exist in the genomes of Old World primates with species-specific patterns. Evidence of intrachromosomal recombination between the two long terminal repeats of HERV-K(C4) is found near the huntingtin locus on chromosome 4. It is possible that members of HERV-K(C4) are involved in genetic instabilities including the RCCX modules, and in protecting the host genome from retroviral attack through an antisense strategy.


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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Andrew W. Dangel
    • 1
  • Anna R. Mendoza
    • 1
  • C. D. Menachery
    • 2
  • Bradley J. Baker
    • 1
    • 2
    • 3
  • Charles M. Daniel
    • 1
  • Michael C. Carroll
    • 4
  • Lai-Chu Wu
    • 2
    • 5
  • C. Yung Yu
    • 1
    • 2
    • 3
    • 6
  1. 1.Children's Hospital Research FoundationColumbusUSA
  2. 2.The Ohio State University Biochemistry ProgramColumbusUSA
  3. 3.Department of PediatricsThe Ohio State UniversityColumbusUSA
  4. 4.Department of PathologyHarvard Medical SchoolBostonUSA
  5. 5.Departments of Internal Medicine and Medical BiochemistryThe Ohio State UniversityColumbusUSA
  6. 6.Department of Medical Microbiology and ImmunologyThe Ohio State UniversityColumbusUSA

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