Hotspots of homologous recombination in mouse meiosis |
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| Institution: | 1. Department of Medicine, University of Washington, Seattle, WA, USA;2. South African Tuberculosis Vaccine Initiative and Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa;3. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA;4. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;1. D S Kothari Centre for Research and Innovation in Science Education, Miranda House, and Department of Zoology, Miranda House, University of Delhi, Delhi 110007, India;2. Open Source Drug Discovery Unit, Council of Scientific and Industrial Research (CSIR), Delhi 110001, India;1. Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands;2. Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands |
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| Abstract: | The molecular mapping of recombinational breakpoints in the proximal region of the mouse MHC has revealed four hotspots at which breakpoints are clustered. A direct comparison of the nucleotide sequences of two independent hotspots revealed common molecular elements: a consensus sequence of the middle-repetitive MT-family, a repeat of tetramer sequences and a sequence homologous to a solitary LTR of mouse retroviruses. Extremely high frequency of recombination is observed at these hotspots when particular MHC haplotypes are used in genetic crosses. Wild mouse-derived wm7 haplotype instigates recombination at the hotspot located at the 3′-end of the Lmp-2 gene only during female meiosis. Fine genetic analysis demonstrated that the wm7 haplotype carries a genetic factor to instigate recombination and another factor to suppress recombination specifically during male meiosis. In addition, there is no dose effect of the hotspot on frequency of recombination. Finally, we described an attempt to establish an efficient in vitro assay system for monitoring recombination using plasmid DNAs that contain the Lmp-2 hotspot and nuclear extracts prepared from mouse testis. |
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