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Meiotic recombination and flanking marker exchange at the highly unstable human minisatellite CEB1 (D2S90)

By Jérôme Buard, Angela C. Shone and Alec J. Jeffreys

Abstract

©2000 by The American Society of Human Genetics. Also available from the journal website at http://www.journals.uchicago.edu/AJHG/home.htmlUnequal crossover has long been suspected to play a role in the germline-specific instability of tandem-repeat DNA, but little information exists on the dynamics and processes of unequal exchange. We have therefore characterized new length alleles associated with flanking-marker exchange at the highly unstable human minisatellite CEB1, which mutates in the male germline by a complex process often resulting in the gene conversion–like transfer of repeats between alleles. DNA flanking CEB1 is rich in single-nucleotide polymorphisms (SNPs) and shows extensive haplotype diversity, consistent with elevated recombinational activity near the minisatellite. These SNPs were used to recover mutant CEB1 molecules associated with flanking-marker exchange, directly from sperm DNA. Mutants with both proximal and distal flanking-marker exchange were shown to contribute significantly to CEB1 turnover and suggest that the 5' end of the array is very active in meiotic unequal crossover. Coconversions involving the interallelic transfer of repeats plus immediate flanking DNA were also common, were also polarized at the 5' end of CEB1, and appeared to define a conversion gradient extending from the repeat array into adjacent DNA. Whereas many mutants associated with complete exchange resulted in simple recombinant-repeat arrays that show reciprocity, coconversions were highly gain-biassed and were, on average, more complex, with allele rearrangements similar\ud to those seen in the bulk of sperm mutants. This suggests distinct recombination-processing pathways producing, on the one hand, simple crossovers in CEB1 and, on the other hand, complex conversions that sometimes extend into flanking DNA

Publisher: University of Chicago Press
Year: 2000
OAI identifier: oai:lra.le.ac.uk:2381/340

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  1. (1998). Analysis of distribution in the human, pig, and rat genomes points toward a general sub-telomeric origin of minisatellite structures. doi
  2. (1988). Clustering of hypervariable minisatellites in the proterminal regions of human autosomes. doi
  3. (1997). Somatic mutation processes at a human minisatellite. Hum Mol Genet 6:129–136 doi
  4. (2000). tional Research Scholars Award from the Howard Hughes Medical Institute and in part by grants from the Wellcome Trust, the Medical Research Council, and the Royal Society (all to A.J.J.). J.B. is a Medical Research Council fellow.

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