The 200 mammals project: sequencing genomes by a novel cost-effective method, yielding a high resolution annotation of the human genome.

遗传学研究确定了人类基因组中与疾病相关的区域， 潜在致病变异的数量。优先考虑这些变体进行后续功能研究是一个 这是当今遗传研究中最重要的问题，但现有的数据集缺乏所需的精确度。 我们建议使用一种新的具有成本效益的基因组组装方法， 胎盘哺乳动物，然后为人类基因组制作一个全面的注释资源， 以及灵长类、啮齿类和狗。这将增加对功能和进化的理解 并使优先突变，疾病和生物功能， 在不同的时间尺度上出现。 我们将选择150个胎盘哺乳动物与圣地亚哥动物园合作进行测序。在 结合约50个现有的高质量胎盘哺乳动物组件，我们的目标是实现 每个家族一个测序的胎盘哺乳动物。我们将使用新的组装方法：DISCOVAR de novo， 其允许仅使用单次测序来产生高质量的新基因组组装体 库类型。因此，我们将把新基因组组装的测序成本降低十倍， 需要少量正常质量的DNA，解决了这类项目的两个主要问题。 我们将把我们新的150个胎盘哺乳动物装配体，沿着与已经存在的50个装配体对齐 一起，然后将使用它来注释人类的许多蛋白质编码和非编码特征。 基因组，沿着保守性（相似性）得分。我们将进行类似的分析， 人类基因组的所有组件，小鼠基因组的所有啮齿动物组件和所有Laurasiatheria 组装到狗的基因组上此外，我们将分析大规模疾病遗传学数据集， 优先考虑致病变异，确定转录因子结合位点转换率，并检查 趋同进化和胎盘哺乳动物之间的基因型-表型相关。 总的来说，这项工作将为基因组学界带来重要的新资源： 哺乳动物基因组和保护跟踪和分析，以帮助发现进化上重要的 和致病变种。合作者包括生物学和保护专家莱德博士， 布罗德研究所和SciLifeLab基因组学平台，测序专家，Haussler博士， UCSC基因组浏览器和一个分析师联盟：Bejerano博士，Marques-Bonet，Lewin，Taipale， 和庞廷，他们都是比较基因组学领域杰出的计算生物学家。

Genetic studies identify regions of the human genome associated with disease, and containing large numbers of potentially causative variants. Prioritizing these variants for follow-up functional studies is one of the foremost issues in genetic research today, but existing datasets lack the precision that is needed. We propose to use a new cost-effective genome assembly method in the sequencing of 150 additional placental mammals, and then to produce a comprehensive annotation resource for the human genome as well as for primates, rodents, and dogs. This will increase the understanding of the function and evolution of the human genome and enable the prioritization mutations that diseases and biological functions that have emerged over a variety of time-scales. We will select 150 placental mammals for sequencing in collaboration with the San Diego Zoo. In combination with the ~50 already existing high quality placental mammalian assemblies, we aim to achieve one sequenced placental mammal per family. We will use the new assembly method: DISCOVAR de novo, which allows the production of a good quality novel genome assembly using only a single sequencing library type. We will thus reduce the sequencing costs of new genome assemblies ten-fold and will only require small amounts of normal-quality DNA, solving two of the major problems for projects of this nature. We will align our new 150 placental mammalian assemblies, along with the 50 already existing assemblies together, and will then use this to annotate many protein-coding and non-coding features of the human genome, along with a conservation (similarity) score. We will perform a similar analysis aligning all primate assemblies to the human genome, all rodent assemblies to the mouse genome and all Laurasiatheria assemblies to the dog genome. In addition, we will analyse large-scale disease genetics datasets to prioritize causative variants, determine rates of transcription factor binding site turnover and examine convergent evolution and genotype-phenotype correlation across placental mammals. Overall, this work will yield important new resources for the genomics community: a wealth of new mammalian genomes and conservation tracks and analysis to aid the discovery of evolutionarily important and disease-causing variants. Collaborators include Dr. Ryder, an expert in phylogeny and conservation, the Broad Institute and SciLifeLab Genomics Platforms, experts in sequencing, Dr. Haussler, leader of the UCSC Genome Browser, and a consortium of analysts: Drs. Bejerano, Marques-Bonet, Lewin, Taipale, and Ponting, all of whom are outstanding computational biologists in the field of comparative genomics.