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
Aw. Dangel et al., 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, Immunogenetics, 40(6), 1994, pp. 425-436
The human complement C4 genes in the HLA exhibit an unusual, dichotomo
us size polymorphism and a four-gene, modular variation involving nove
l gene RP, complement C4, steroid 21-hydroxylase (CYP21), and tenascin
-like Gene X (RCCX). The C4 gene size dichotomy is mediated by an endo
genous retrovirus, HERV-K(C4). Nearly identical sequences for this ret
rotransposon are present precisely at the same location in the long C4
genes from the tandem RCCX Module I and Module II. Specific nucleotid
e substitutions between the long and short C4 genes have been identifi
ed and used for diagnosis. Southern blot analyses revealed that HERV-K
(C4) is present at more than 30 locations in the human genome, exhibit
s variations in the population, and its analogs exist in the genomes o
f Old World primates with species-specific patterns. Evidence of intra
chromosomal recombination between the two long terminal repeats of HER
V-K(C4) is found near the hunting-tin locus on chromosome 4. It is pos
sible that members of KERV-K(C4) are involved in genetic instabilities
including the RCCX modules, and in protecting the host genome from re
troviral attack through an antisense strategy.