Allelic recombination between distinct genomic locations generates copy number diversity in human beta-defensins.
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.
Abu Bakar
Suhaili
S
Institute of Genetics, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
Hollox
Edward J
EJ
Armour
John A L
JA
D000483:Alleles; D018628:Gene Dosage; D006801:Humans; D009154:Mutation; D011995:Recombination, Genetic; D020080:Tandem Repeat Sequences; D023083:beta-Defensins / Q000235:genetics*
D023083:beta-Defensins