Chromosome-Wide Mapping of Recombinational Activity

我们的目标是产生第一个高分辨率的哺乳动物重组活动的地图， 染色体作为整个基因组的代表，包括热点位置的变化， 种内和种间的活性，以及这在F1动物中与相互杂交和种间杂交的差异 雄性和雌性减数分裂。为此，我们将绘制来自六个遗传标记中的每一个的3000次减数分裂中产生的重组体。 交叉点的分辨率低于50 Kb，使我们能够区分各个热点，并检测低至 0.03 cM/热点。这些数据将有助于我们理解哺乳动物重组作为一种生物学行为， 过程以及重组参数与染色体其他方面的关系 动力学 目标5a。我们将绘制出6个遗传杂交中8号染色体上每个杂交的位置， 每个后代总共18，000次减数分裂，分辨率低于50 kb。其中四个十字架将是女性F1 以菊花链设计（C57 BL/6 J x PWD/PhJ x WSB/EiJ x CAST/EiJ x C57 BL/6 J）创建的混合动力车，然后 回交转育到C57 BL/6 J。来自C57 BL/6 J × PWD/PhJ和WSB/EiJ × CAST/EiJ杂交的F1雄性杂种 也将回交到C57 BL/6 J。尽可能从F1中获得相同数量的减数分裂 通过原始亲本（AxB和BXA）的相互杂交产生的动物。该设计最适合于 收集关于这些杂交中的遗传变异性、性别特异性和可能的印记效应的数据。 目标5 b。利用aim 5a的数据，我们将分析位置的菌株，性别和横向特异性， 重组热点沿着8号染色体长度的分布和活性。对于理解 在进化过程中，我们还将提供一个跨亚种的8号染色体热点的共识图。 目标5c。我们将使18，000个回交DMA样本通过一个科学界提供给科学界。 知识库，将在8号染色体上新开发的3000种SNP检测方法将发布在我们的 网站，并提供给其他QTL和基因定位研究。

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