Abstract

Understanding the genomic distribution of mammalian recombination is a matter of considerable importance for 1) optimizing strategies for association studies mapping human disease genes by linkage disequilibrium, 2) optimizing experimental strategies for mapping and cloning genes in experimental mammals, 3) understanding the role of recombinational hotspots in evolutionary processes, and 4) understanding genetic recombination as a biological process. ? ? The purpose of the proposed research is to provide a molecular description of the locations and properties of hotspots in a sample of the mouse genome. We will map to a resolution of 1.5 Kb, the locations of 900-1000 crossovers occurring in five 5-megabase regions of the mouse genome, selected for specific characteristics. The crossovers, which we expect to describe nearly 80 recombinational hotspots, will be identified in DNAs from (C57BL/6J x CAST/EiJ) F2 progeny. Our hotspot characterizations will provide the locations and recombination frequencies of all hotspots down to a level of 0.02 cM/hotspot, and will include the haplotype and sex specificity of each hotspot. To our knowledge, this will be the first such large-scale effort for a mammal. Informatics studies will attempt to identify key hotspot sequences and chromosomal features that define hotspot locations. Additionally, for one of the chromosomal regions, we will carry out a genetic test for the existence of trans-acting genes required for hotspot activity. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM078643-02
Application #
7163014
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Portnoy, Matthew
Project Start
2006-01-01
Project End
2009-12-31
Budget Start
2007-01-01
Budget End
2007-12-31
Support Year
2
Fiscal Year
2007
Total Cost
$309,943
Indirect Cost

  Institution

Name
Jackson Laboratory
Department
Type
DUNS #
042140483
City
Bar Harbor
State
ME
Country
United States
Zip Code
04609

  Publications

Parvanov, Emil D; Tian, Hui; Billings, Timothy et al. (2017) PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis. Mol Biol Cell 28:488-499
Baker, Christopher L; Kajita, Shimpei; Walker, Michael et al. (2015) PRDM9 drives evolutionary erosion of hotspots in Mus musculus through haplotype-specific initiation of meiotic recombination. PLoS Genet 11:e1004916
Walker, Michael; Billings, Timothy; Baker, Christopher L et al. (2015) Affinity-seq detects genome-wide PRDM9 binding sites and reveals the impact of prior chromatin modifications on mammalian recombination hotspot usage. Epigenetics Chromatin 8:31
Baker, Christopher L; Petkova, Pavlina; Walker, Michael et al. (2015) Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots. PLoS Genet 11:e1005512
Baker, Christopher L; Walker, Michael; Kajita, Shimpei et al. (2014) PRDM9 binding organizes hotspot nucleosomes and limits Holliday junction migration. Genome Res 24:724-32
Billings, Timothy; Parvanov, Emil D; Baker, Christopher L et al. (2013) DNA binding specificities of the long zinc-finger recombination protein PRDM9. Genome Biol 14:R35
Paigen, Kenneth; Petkov, Petko (2012) Meiotic DSBs and the control of mammalian recombination. Cell Res 22:1624-6
Paigen, Kenneth; Petkov, Petko (2010) Mammalian recombination hot spots: properties, control and evolution. Nat Rev Genet 11:221-33
Parvanov, Emil D; Petkov, Petko M; Paigen, Kenneth (2010) Prdm9 controls activation of mammalian recombination hotspots. Science 327:835
Parvanov, Emil D; Ng, Siemon H S; Petkov, Petko M et al. (2009) Trans-regulation of mouse meiotic recombination hotspots by Rcr1. PLoS Biol 7:e36

Showing the most recent 10 out of 13 publications