title: Mutation mechanisms that underlie turnover of a human telomere-adjacent segmental duplication containing an unstable minisatellite.
abstract: Subterminal regions, juxtaposed to telomeres on human chromosomes, contain a high density of segmental duplications, but relatively little is known about the evolutionary processes that underlie sequence turnover in these regions. We have characterized a segmental duplication adjacent to the Xp/Yp telomere, each copy containing a hypervariable array of the DXYS14 minisatellite. Both DXYS14 repeat arrays mutate at a high rate (0.3 and 0.2% per gamete) but linkage disequilibrium analysis across 27 SNPs and a direct crossover assay show that recombination during meiosis is suppressed. Therefore instability at DXYS14a and b is dominated by intra-allelic processes or possibly conversion limited to the repeat arrays. Furthermore some chromosomes (14%) carry only one copy of the duplicon, including one DXYS14 repeat array that is also highly mutable (1.2% per gamete). To explain these and other observations, we propose there is another low-rate mutation process that causes copy number change in part or all of the duplicon.
authors.affiliation: Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Hills
authors.forename: Jennie N
authors.initials: JN
authors.lastname: Jeyapalan
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Foxon
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Royle
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D003434:Crossing Over, Genetic; D020440:Gene Duplication; D006801:Humans; D007700:Kinetics; D015810:Linkage Disequilibrium; D018598:Minisatellite Repeats; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D016615:Telomere / Q000378:metabolism*