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Human Molecular Genetics Advance Access published online on September 9, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi332
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© The Author 2005. Published by Oxford University Press. All rights reserved
Received August 3, 2005
Revised August 26, 2005
Accepted August 26, 2005

Article

Discontinuities and unsynapsed regions in meiotic chromosomes have a cis effect on meiotic recombination patterns in normal human males

Fei Sun 1, Maria Oliver-Bonet 1, Thomas Liehr 2, Heike Starke 2, Kiril Trpkov 3, Evelyn Ko 4, Alfred Rademaker 5, and Renée H. Martin 6*

1 Department of Medical Genetics, University of Calgary, Calgary, Canada T2N 4N1; Department of Genetics, Alberta Children's Hospital, Calgary, Canada T2T 5C7
2 Institute of Human Genetics and Anthropology, 07743 Jena, Germany
3 Department of Pathology, Rockyview Hospital, Calgary, Canada, T2V 1P9
4 Department of Genetics, Alberta Children's Hospital, Calgary, Canada T2T 5C7
5 Cancer Center Biometry Section, Northwestern University Medical School, Chicago, USA, 60611-4402
6 Department of Medical Genetics, University of Calgary, Calgary, Canada T2N 4N1; Department of Genetics, Alberta Children's Hospital, 1820 Richmond Road S.W., Calgary, Alberta, Canada T2T 5C7

* To whom correspondence should be addressed.
Renée H. Martin, E-mail: rhmartin{at}ucalgary.ca


  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 to 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.


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