title: Evidence for a fast, intrachromosomal conversion mechanism from mapping of nucleotide variants within a homogeneous alpha-satellite DNA array.
abstract: Assuming that patterns of sequence variants within highly homogeneous centromeric tandem repeat arrays can tell us which molecular turnover mechanisms are presently at work, we analyzed the alpha-satellite tandem repeat array DXZ1 of one human X chromosome. Here we present accurate snapshots from this dark matter of the genome. We demonstrate stable and representative cloning of the array in a P1 artificial chromosome (PAC) library, use samples of higher-order repeats subcloned from five unmapped PACs (120-160 kb) to identify common variants, and show that such variants are presently in a fixed transition state. To characterize patterns of variant spread throughout homogeneous array segments, we use a novel partial restriction and pulsed-field gel electrophoresis mapping approach. We find an older large-scale (35-50 kb) duplication event supporting the evolutionarily important unequal crossing-over hypothesis, but generally find independent variant occurrence and a paucity of potential de novo mutations within segments of highest homogeneity (99.1%-99.3%). Within such segments, a highly nonrandom variant clustering within adjacent higher-order repeats was found in the absence of haplotypic repeats. Such variant clusters are hardly explained by interchromosomal, fixation-driving mechanisms and likely reflect a fast, localized, intrachromosomal sequence conversion mechanism.
authors.affiliation: Institute of Human Genetics, Technical University of Munich, Munich, Germany. dirk@pedgen.med.uni-muenchen.de
authors.forename: Dirk
authors.initials: D
authors.lastname: Schindelhauer
authors.forename: Tobias
authors.initials: T
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D002503:Centromere / Q000235:genetics; D027042:Chromosomes, Artificial, P1 Bacteriophage / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics*; D005785:Gene Conversion / Q000235:genetics*; D020440:Gene Duplication; D014644:Genetic Variation / Q000235:genetics*; D006071:Gorilla gorilla; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011995:Recombination, Genetic / Q000235:genetics; D015183:Restriction Mapping / Q000379:methods*; D014960:X Chromosome / Q000235:genetics
chemical_list: D004276:DNA, Satellite; D009711:Nucleotides