title: A recurrent breakpoint in the most common deletion of the Ig heavy chain locus (del A1-GP-G2-G4-E).
abstract: Human Ig heavy chain constant regions are encoded by a cluster of genes, the IGHC locus, on 14q32.3. Several forms of IGHC deletions and duplications spanning one to five genes have been described in different populations, with frequencies of 1.5-3.5% and 4.5-44%, respectively. Despite the common occurrence of these gene rearrangements, little is known about the breakpoint sites; evidence obtained from deletions in the IGHC locus and in other regions of the human genome suggests that they preferentially occur in highly homologous regions and might be favored by a variety of recombinogenic signals. We present here a detailed study of three homozygotes for the most common type of IGHC multiple gene deletion, spanning the A1-GP-G2-G4-E genes. Using a combination of Southern blotting, long-range PCR, and automated sequencing, the unequal crossover events of all of the six studied haplotypes have been mapped to a region of approximately 2 kb with almost complete homology between EP1-A1 and E-A2, flanked by two minisatellites. These results are consistent with the hypothesis that segments of complete homology may be required for efficient homologous recombination in humans. The possible role of minisatellites as recombination signals is inferred, in agreement with current knowledge.
authors.affiliation: Dipartimento di Genetica, Biologia e Biochimica, Università di Torino, Italy. a.brusco@cios.to.cnr.it
authors.forename: A
authors.initials: A
authors.lastname: Brusco
authors.forename: S
authors.initials: S
authors.lastname: Saviozzi
authors.forename: F
authors.initials: F
authors.lastname: Cinque
authors.forename: A
authors.initials: A
authors.lastname: Bottaro
authors.forename: M
authors.initials: M
authors.lastname: DeMarchi
mesh_terms: D015139:Blotting, Southern; D002874:Chromosome Mapping; D003434:Crossing Over, Genetic / Q000276:immunology; D017353:Gene Deletion; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007137:Immunoglobulin alpha-Chains / Q000235:genetics; D007139:Immunoglobulin epsilon-Chains / Q000235:genetics; D007142:Immunoglobulin gamma-Chains / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology*; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA
chemical_list: D007143:Immunoglobulin Heavy Chains; D007137:Immunoglobulin alpha-Chains; D007139:Immunoglobulin epsilon-Chains; D007142:Immunoglobulin gamma-Chains