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Allelic recombination between distinct genomic locations generates copy number diversity in human β-defensins

Bakar, Suhaili Abu, Hollox, Edward J., Armour, John A.L.
Proceedings of the National Academy of Sciences of the United States of America 2009 v.106 no.3 pp. 853-858
chromosome mapping, diploidy, genes, genome assembly, haplotypes, humans, innate immunity, loci, meiosis, signal peptide
β-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 [almost equal to]5 Mb apart on chromosome band 8p23.1, contradicting the most recent genome assembly. We also demonstrate that the predominant mechanism of change in β-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 [almost equal to]0.7% per gamete. This places it among the fastest-changing copy number variants currently known.