Human Molecular Genetics Advance Access originally published online on May 23, 2008
Human Molecular Genetics 2008 17(17):2583-2594; doi:10.1093/hmg/ddn158
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Variation in crossover interference levels on individual chromosomes from human males
1 Hefei National Laboratory for Physical Sciences at Microscale 2 School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China 3 Department of Medical Genetics, University of Calgary, Calgary, Canada T2 N 4N1 4 Institute of Human Genetics and Anthropology, 07743 Jena, Germany 5 Department of Urology 6 Department of Obstetrics and Gynecology 7 Department of Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143-1695, USA
* To whom correspondence should be addressed at: Department of Medical Genetics, University of Calgary, 3330 Hospital Dr, NW, Calgary, AB, Canada T2 N 1N4. Tel: +1 4032207520; Fax: +1 4032107931; Email: rhmartin{at}ucalgary.ca or feisun{at}ustc.edu.cn
Received April 7, 2008; Accepted May 20, 2008
Crossovers (COs) generated by homologous recombination ensure the proper segregation of chromosomes during meiosis. COs exhibit interference, which leads to widely spaced COs along chromosomes. Strong positive CO interference has been found in humans. However, little is known about the extent of human CO interference. In this study, variations in CO interference over the entire human genome and among individuals were analyzed by immunofluorescence combined with fluorescence in situ hybridization of testicular biopsies from 10 control men. These methods allow for direct identification of the frequency and location of COs in specific chromosomes of pachytene cells. The strength of CO interference was estimated by fitting the frequency distribution of inter-CO distances to the gamma model. Positive interference among CO on chromosomes was observed in these men, and the strength of inter-arm interference was significantly stronger than that for intra-arm CO. In addition, interference was observed to act across the centromere. Significant inter-individual and inter-chromosomal variations in the levels of interference were found, with smaller chromosomes exhibiting stronger interference. Discontinuous chromosome regions (gaps) and unsynapsed chromosome regions (splits) in chromosome 9 had both cis and trans effects on CO interference levels. This is the first report that the interference level varies significantly across the whole genome and that, at least in the human male, anomalies in chromosome synapsis play an important role in altering CO interference levels.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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