title: Discontinuities and unsynapsed regions in meiotic chromosomes have a cis effect on meiotic recombination patterns in normal human males.
abstract: During meiosis, homologous chromosome pairing is essential for subsequent meiotic recombination (crossover). Discontinuous chromosome regions (gaps) or unsynapsed chromosome regions (splits) in the synaptonemal complex (SC) indicate anomalies in chromosome synapsis. Recently developed immunofluorescence techniques (using antibodies against SC proteins and the crossover-associated MLH1 protein) were combined with fluorescence in situ hybridization (using centromere-specific DNA probes) to identify bivalents with gaps/splits and to examine the effect of gaps/splits on meiotic recombination patterns during the pachytene stage of meiotic prophase from three normal human males. Gaps were observed only in the heterochromatic regions of chromosomes 9 and 1, with 9q gaps accounting for 90% of these events. Most splits were also found in chromosomes 9 and 1, with 58% of splits occurring on 9q. Gaps and splits significantly altered the distribution of MLH1 foci on the SC. On gapped SC 9q, the frequency of MLH1 foci was decreased compared with controls, and single 9q crossovers tended toward a more distal distribution. Furthermore, the larger the gap the more distal the location of the MLH1 focus closest to the q arm's telomere. MLH1 foci on split SC 9 had distributions similar to those of gapped SC 9; however, splits did not change the frequencies of MLH1 foci on SC 9. This is the first demonstration that gaps and splits have an effect on meiotic recombination in humans.
authors.affiliation: Department of Medical Genetics, University of Calgary, Alberta, Canada.
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.forename: Maria
authors.initials: M
authors.lastname: Oliver-Bonet
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Heike
authors.initials: H
authors.lastname: Starke
authors.forename: Kiril
authors.initials: K
authors.lastname: Trpkov
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ko
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
authors.forename: Renée H
authors.initials: RH
authors.lastname: Martin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics; D002503:Centromere / Q000235:genetics; D023902:Chromosome Pairing / Q000235:genetics / Q000502:physiology; D002877:Chromosomes, Human / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000378:metabolism; D002899:Chromosomes, Human, Pair 9 / Q000378:metabolism; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics*; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D013090:Spermatocytes / Q000166:cytology; D013573:Synaptonemal Complex / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1