title: Allelic recombination between distinct genomic locations generates copy number diversity in human beta-defensins.
abstract: Beta-defensins are small secreted antimicrobial and signaling peptides involved in the innate immune response of vertebrates. In humans, a cluster of at least 7 of these genes shows extensive copy number variation, with a diploid copy number commonly ranging between 2 and 7. Using a genetic mapping approach, we show that this cluster is at not 1 but 2 distinct genomic loci approximately 5 Mb apart on chromosome band 8p23.1, contradicting the most recent genome assembly. We also demonstrate that the predominant mechanism of change in beta-defensin copy number is simple allelic recombination occurring in the interval between the 2 distinct genomic loci for these genes. In 416 meiotic transmissions, we observe 3 events creating a haplotype copy number not found in the parent, equivalent to a germ-line rate of copy number change of approximately 0.7% per gamete. This places it among the fastest-changing copy number variants currently known.
authors.affiliation: Institute of Genetics, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
authors.forename: Suhaili
authors.initials: S
authors.lastname: Abu Bakar
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hollox
authors.forename: John A L
authors.initials: JA
authors.lastname: Armour
mesh_terms: D000483:Alleles; D018628:Gene Dosage; D006801:Humans; D009154:Mutation; D011995:Recombination, Genetic; D020080:Tandem Repeat Sequences; D023083:beta-Defensins / Q000235:genetics*
chemical_list: D023083:beta-Defensins