title: 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.
abstract: 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.
authors.affiliation: Children's Hospital Research Foundation, Columbus, OH 43205.
authors.forename: A W
authors.initials: AW
authors.lastname: Dangel
authors.forename: A R
authors.initials: AR
authors.lastname: Mendoza
authors.forename: B J
authors.initials: BJ
authors.lastname: Baker
authors.forename: C M
authors.initials: CM
authors.lastname: Daniel
authors.forename: M C
authors.initials: MC
authors.lastname: Carroll
authors.forename: L C
authors.initials: LC
authors.lastname: Wu
authors.forename: C Y
authors.initials: CY
authors.lastname: Yu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002520:Cercopithecidae / Q000235:genetics* / Q000821:virology; D003181:Complement C4 / Q000235:genetics*; D004247:DNA; D004279:DNA, Viral; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009154:Mutation; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D012190:Retroviridae / Q000235:genetics*; D016415:Sequence Alignment; D013045:Species Specificity
chemical_list: D003181:Complement C4; D004279:DNA, Viral; D004247:DNA