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Human Molecular Genetics Advance Access originally published online on June 27, 2006
Human Molecular Genetics 2006 15(15):2376-2391; doi:10.1093/hmg/ddl162
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Variation in MLH1 distribution in recombination maps for individual chromosomes from human males

Fei Sun1,2, Maria Oliver-Bonet1,2, Thomas Liehr3, Heike Starke3, Paul Turek4,5, Evelyn Ko2, Alfred Rademaker6 and Renée H. Martin1,2,*

1 Department of Medical Genetics, University of Calgary, Calgary, Canada T2N 4N1, 2 Department of Genetics, Alberta Children's Hospital, 1820 Richmond Road S.W., Calgary, Alberta, Canada T2T 5C7, 3 Institute of Human Genetics and Anthropology, 07743 Jena, Germany, 4 Department of Urology, University of California San Francisco, San Francisco, CA 94143-1695, USA, 5 Department of Obstetrics and Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143-1695, USA and 6 Department of Preventive Medicine, Northwestern University Medical School, Chicago, IL 60611-4402, USA

* To whom correspondence should be addressed. Tel: +1 4039437369; Fax: +1 4035439100; Email: rhmartin{at}ucalgary.ca

Received April 18, 2006; Revised May 22, 2006; Accepted June 22, 2006

Meiotic recombination is essential for the segregation of homologous chromosomes and the formation of normal haploid gametes. Little is known about patterns of meiotic recombination in human germ cells or the mechanisms that control these patterns. Documentation of the normal range of variability of recombination distribution over the genome among individuals is an essential prerequisite for understanding abnormal recombination patterns, which may be associated with non-disjunction and chromosome rearrangements. In this article, variation in recombination maps for individual chromosomes among 10 normal human males is examined for the first time. An immunocytogenetic approach allowed analysis of pachytene cells, using antibodies to detect the mature synaptonemal complex (SCP1/SCP3), the centromere (CREST) and sites of crossing over (MLH1). Individual bivalents were identified with centromere-specific multicolor fluorescence in situ hybridization. Significant heterogeneity in MLH1 focus frequency across donors was observed for larger chromosome arms (P<0.05, one-way ANOVA). Significant inter-donor variation in the overall crossover frequency per cell was also found (P<0.0001, one-way ANOVA). Furthermore, several chromosome arms showed significant differences in crossover distribution along the SCs among donors. Inter-individual variation in interference distances was observed for all chromosomes. The significance of altered recombination patterns among individuals and the role of interference are discussed.


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