Generating the next generation of genomics resources for biomedical investigation using a powerful and cost-effective genome assembly strategy

 描述（由申请人提供） 揭开人类健康和疾病的遗传基础需要高质量的基因组信息。因此，该社区依赖于一个单一的，单倍体人类参考序列，不代表任何单个人的实际基因组序列。虽然这种资源对于绘制许多导致人类正常和疾病变异的遗传变异非常有益，但它可能会限制许多类型的分析。此外，这种单一参考模型可能导致分析所有人群的遗传变异的能力不均衡。 同样，非人类灵长类动物的基因组对于理解我们自己的基因组也至关重要。虽然有许多灵长类动物基因组草图，包括所有的类人猿，但这些基因组的质量和连续性都低于人类参考基因组。重要的是，这些基因组的染色体尺度支架通常是通过与人类参考进行比较来完成的。虽然这种近似通常是正确的，但知道哪里是错误的至关重要。 使用一种彻底创新和简单的方法，我们现在可以生成人类和非人类灵长类动物基因组的高度连续的从头组装。这种方法需要亚微克数量的DNA，可以在几个月内从头到尾完成，包括测序时间。我们的方法使用来自体外组装的染色质的邻近连接的基因组邻接信息。它利用高通量测序的速度和成本效益来产生大量的单倍型定相的邻接数据，长度超过100个碱基。使用这种方法，我们将从50个人类和12个非人类灵长类动物中产生从头组装的基因组，这些基因组具有高准确性，部分单倍型定相，支架N50的长度预计在10到20 Mb之间。

 DESCRIPTION (provided by applicant) Unravelling the genetic basis of human health and disease requires high-quality genome information. Heretofore, the community has relied on a single, haploid human reference sequence that does not represent the actual genome sequence of any single person. While this resource has been enormously beneficial for mapping many of the genetic variants responsible for human normal and disease variation, it can limit many types of analyses. Further, this single-reference model can cause uneven power to analyze genetic variation across all human populations. Similarly, non-human primate genomes are also fundamentally important for understanding our own genome. While many draft primate genome assemblies are available, including for all great apes, these genomes are all of lower quality and contiguity than the human reference genome. Importantly, chromosome-scale scaffolding of these genomes was often done by comparison to the human reference. While this approximation is generally correct, knowing where this is wrong is critically important. Using a radically innovative and simple approach, we can now generate highly contiguous de novo assemblies of human and non-human primate genomes. The approach requires sub- microgram quantities of DNA and can be carried done from start to finish within a few months, including sequencing time. Our approach uses genome contiguity information as derived from proximity ligation of in vitro assembled chromatin. It harnesses the speed and cost-effectiveness of high-throughput sequencing to generate large amounts of haplotype-phased contiguity data spanning well over 100 kilobases in length. Using this approach we will generate de novo assembled genomes from 50 humans and 12 non-human primates of high accuracy, partially haplotype phased, with scaffold N50s expected to be between 10 and 20 Mb in length.