title: Characterization of the recombination hot spot involved in the genomic rearrangement leading to the hybrid D-CE-D gene in the D(VI) phenotype.
abstract: In the Caucasian population, the RH locus of RhD-positive individuals is composed of two homologous genes, RHD and RHCE, arranged in tandem but of a single gene, RHCE, in RhD-negative individuals. Many variants recently characterized carry rearranged RH genes, most often by an unidirectional segmental DNA-exchange (gene-conversion) event. In D(VI) variants of type II, RHD is a D-CE-D hybrid gene in which the DNA fragment carrying exons 4-6 has been replaced by the corresponding sequences from the RHCE gene. To identify precisely and characterize the two transition sites, we have studied, by both PCR and sequence analysis, a genomic region between the 3' end of intron 3 and exon 7 in normal RHCE and RHD genes as well as in D(VI) DNA. We show that the D-CE breakpoint is located in intron 3, within a 250-bp fragment comprising an Alu S sequence, and that the CE-D breakpoint lies within a 39-bp fragment in intron 6. This Alu S sequence (and the 100-bp region immediately downstream) most likely defines a recombination hot spot, since there lies also the 5' breakpoint of different rearrangement events leading to D-CE and CE-D transitions in hybrid D(VI),DFR and Dc-,R(N) gene complexes, respectively.
authors.affiliation: INSERM U76, Institut National de la Transfusion Sanguine, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Matassi
authors.forename: B
authors.initials: B
authors.lastname: Chérif-Zahar
authors.forename: I
authors.initials: I
authors.lastname: Mouro
authors.forename: J P
authors.initials: JP
authors.lastname: Cartron
mesh_terms: D001483:Base Sequence; D005091:Exons / Q000235:genetics; D015321:Gene Rearrangement; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D015183:Restriction Mapping; D012204:Rh-Hr Blood-Group System / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid
chemical_list: D012204:Rh-Hr Blood-Group System