title: Recombination breakpoints in the human beta-globin gene cluster.
abstract: The human beta-globin gene complex spans a region of 70 kb and contains numerous sequence variants. These variant sites form a 5' cluster (5' beta-haplotype) and a 3' cluster (3' beta-haplotype) with strong linkage disequilibrium among the sites within each cluster, but not between the two clusters. The 9-kb region between the 5' and 3' clusters has been estimated to have rates of recombination that are 3 to 30 times normal, and the region has therefore been proposed as a 'hotspot' of recombination. We describe three families with evidence of meiotic recombination within this 'hotspot' of the beta-globin gene cluster and in which the cross-over breakpoints have been defined at the sequence level. In one family, the recombination has occurred in the maternal chromosome within a region of 361 bp between positions -911 and -550 5' to the beta-globin gene. In the other two families, the recombination has occurred in the paternal chromosome within a region of approximately 1,100 bp between positions -542 and +568 relative to the beta-globin gene cap site. Both regions occur within the 2-kb region of replication initiation (IR) in the beta-globin gene domain with no overlap. The IR region contains a consensus sequence for a protein (Pur), which binds preferentially to single-stranded DNA, a role implicated in recombination events.
authors.affiliation: MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Smith
authors.forename: P J
authors.initials: PJ
authors.lastname: Ho
authors.forename: J B
authors.initials: JB
authors.lastname: Clegg
authors.forename: J R
authors.initials: JR
authors.lastname: Kidd
authors.forename: S L
authors.initials: SL
authors.lastname: Thein
mesh_terms: D002874:Chromosome Mapping; D005260:Female; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D005810:Multigene Family; D011995:Recombination, Genetic
chemical_list: D005914:Globins