Genetic recombination at the human RH locus: a family study of the red-cell Evans phenotype reveals a transfer of exons 2-6 from the RHD to the RHCE gene

Am J Hum Genet. 1996 Oct;59(4):825-33.


The human RH locus appears to consist of two structural genes, D and CE, which map on the short arm p34-36 of chromosome 1 and specify a most complex system of blood-group genetic polymorphisms. Here we describe a family study of the Evans (also known as "D..") phenotype, a codominant trait associated with both qualitative and quantitative changes in D-antigen expression. A cataract-causing mutation was also inherited in this family and was apparently cotransmitted with Evans, suggesting a chromosomal linkage of these two otherwise unrelated traits. Southern blot analysis and allele-specific PCR showed the linkage of Evans with a SphI RFLP marker and the presence of a hybrid gene in the RH locus. To delineate the pattern of gene expression, the composition and structure of Rh-polypeptide transcripts were characterized by reverse transcriptase-PCR and nucleotide sequencing. This resulted in the identification of a novel Rh transcript expressed only in the Evans-positive erythroid cells. Sequence analysis showed that the transcript maintained a normal open reading frame but occurred as a CE-D-CE composite in which exons 2-6 of the CE gene were replaced by the homologous counterpart of the D gene. This hybrid gene was predicted to encode a CE-D-CE fusion protein whose surface expression correlates with the Evans phenotype. The mode and consequence of such a recombination event suggest the occurrence, in the RH locus, of a segmental DNA transfer via the mechanism of gene conversion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alleles
  • Base Sequence
  • Cataract / genetics
  • Chromosomes, Human, Pair 1*
  • DNA, Complementary / chemistry
  • Exons*
  • Female
  • Genetic Linkage
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Recombination, Genetic
  • Rh-Hr Blood-Group System / genetics*


  • DNA, Complementary
  • Rh-Hr Blood-Group System
  • Rho(D) antigen