Chromosome-Wide Mapping of Recombinational Activity

$356,812P50FY2007GMNIH

Jackson Laboratory, Bar Harbor ME

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Abstract

Our goal is to generate the first high-resolution maps of mammalian recombination activity for an entire[unreadable] chromosome as a representative of the genome as a whole, including the variation in hotspot location and[unreadable] activity within and between species, and how this differs in F1 animals from reciprocal crosses and between[unreadable] male and female meiosis. For this we will map recombinants arising in 3000 meioses from each of six genetic[unreadable] crosses at under 50-Kb resolution, enabling us to distinguish individual hotspots and detect activities as low as[unreadable] 0.03 cM/hotspot. These data will go far in helping us understand mammalian recombination as a biological[unreadable] process as well as relationships between parameters of recombination and other aspects of chromosome[unreadable] dynamics.[unreadable] Aim 5a. we will map the location of every crossover on Chromosome 8 arising in six genetic crosses, 3000[unreadable] offspring each for a total of 18,000 meioses, at under 50 kb resolution. Four of the crosses will be female F1[unreadable] hybrids created in a daisy-chain design (C57BL/6J x PWD/PhJ x WSB/EiJ x CAST/EiJ x C57BL/6J) and then[unreadable] backcrossed to C57BL/6J. F1 male hybrids from crosses of C57BL/6J x PWD/PhJ and WSB/EiJ x CAST/EiJ[unreadable] will also be backcrossed to C57BL/6J. Whenever possible, equal numbers of meioses will be derived from F1[unreadable] animals created by reciprocal crosses of the original parents (AxB and BXA). This design is optimal for[unreadable] gathering data on genetic variability, sex specificity, and possible imprinting effects in these crosses.[unreadable] Aim 5b. using the data of aim 5a, we will analyze the strain, sex and cross direction specificity of the location,[unreadable] distribution and activity of the recombination hotspots along the length of Chromosome 8. For understanding[unreadable] evolutionary processes, we will also provide a consensus map of Chromosome 8 hotspots across subspecies.[unreadable] Aim 5c. we will make the 18,000 backcross DMA samples available to the scientific community via a[unreadable] repository, and the 3000 SNP assays that will be newly developed on Chromosome 8 will be posted on our[unreadable] web site and made available to others for QTL and gene mapping studies.

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