Chromosome-Wide Mapping of Recombinational Activity

重组活动的染色体范围图谱

• 批准号: 7299598
• 负责人: Petko M Petkov
• 金额: $ 31.93万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7299598
• 关键词: biochemical evolution; bioinformatics; chromosomes; computational biology; cytogenetics; functional /structural genomics; gender difference; genetic mapping; genetic recombination; meiosis; species difference

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.

我们的目标是生成整个哺乳动物重组活动的第一个高分辨率图谱 染色体作为整个基因组的代表，包括热点位置和变化 物种内和物种间的活动，以及 F1 代动物与互交和物种间的活动有何不同 雄性和雌性减数分裂。为此，我们将绘制 6 个遗传基因中每一个的 3000 个减数分裂中产生的重组体图谱。 交叉分辨率低于 50 Kb，使我们能够区分各个热点并检测低至 0.03 厘米/热点。这些数据将极大地帮助我们理解哺乳动物的重组作为一种生物学行为。 重组过程以及参数与染色体其他方面之间的关系 动力学。 目标 5a。我们将绘制 6 次遗传杂交中 8 号染色体上每次交叉的位置，共 3000 个 每个后代总共有 18,000 个减数分裂，分辨率低于 50 kb。其中四个杂交将是雌性 F1 以菊花链设计创建的混合体（C57BL/6J x PWD/PhJ x WSB/EiJ x CAST/EiJ x C57BL/6J），然后 与C57BL/6J回交。来自 C57BL/6J x PWD/PhJ 和 WSB/EiJ x CAST/EiJ 杂交的 F1 雄性杂种 还将与 C57BL/6J 回交。只要有可能，F1 就会产生相同数量的减数分裂 由原始亲本（AxB 和 BXA）互交产生的动物。该设计最适合 收集有关这些杂交中遗传变异性、性别特异性和可能的​​印记效应的数据。 目标 5b。使用目标5a的数据，我们将分析该位置的应变、性别和横向特异性， 重组热点沿 8 号染色体长度的分布和活性。用于理解 进化过程，我们还将提供跨亚种 8 号染色体热点的共识图。 目标5c。我们将通过以下方式向科学界提供 18,000 个回交 DMA 样本 存储库，并且将在 8 号染色体上新开发的 3000 个 SNP 检测将发布在我们的 网站并提供给其他人进行 QTL 和基因图谱研究。