16 ERA-CAPS: 1001 Genomes Plus

了解遗传变异如何转化为表型变异，以及这种转化如何依赖于环境，是现代生物学的一个重大挑战。它是人类遗传学和农业以及进化生物学的基础。由于技术的进步，现在可以通过对整个人群进行测序并将这些信息与表型数据联系起来来回答这个问题，无论这些表型数据是公共卫生记录，作物产量数据还是在受控实验或自然界中承受压力的能力。（经常被高度宣传）的努力：我们仍然远远没有完全描述种群规模的遗传变异。“下一代”测序方法使筛选大量个体（几乎是神话般的“1000美元人类基因组”）在经济上可行，但实际上并不产生完整的基因组序列-它们产生大量非常短的序列片段，必须与参考基因组进行比对以识别变体。正因为如此，只有简单的变异（单核苷酸和非常短的插入/缺失多态性）被报道，结果总是有偏见的参考基因组中存在或缺失。大的或复杂的结构变体，以及复杂变体中的简单变体通常会被完全忽略。目前还不知道这个问题有多严重，原因很简单，找到答案需要完全组装大量的基因组，并将结果与使用标准方法生成的数据进行比较。这就是1001 G+提案的目标。长读段测序现在已经发展到可以为大样本生成几乎完整的基因组的阶段-至少对于基因组相对较小的生物体来说。在我们成功完成“1001基因组计划”的基础上，我们将从不同的拟南芥菌株中收集至少50个基因组，用转录组和表观基因组信息注释它们，并开发工具将结果提供给社区。这将大大有助于回答我们目前看不到的基因组部分中隐藏着什么的问题--当然是在A。thaliana但是我们的结果（以及我们开发的用于发现、解释和分享序列变异完整信息的工具和概念）将为在基因组更大的生物体中进行类似研究铺平道路，在这些生物体中，隐藏的部分可能相对更大，甚至可能更重要。该项目汇集了一个具有互补技能的研究人员团队，相当多的管理专业知识和良好的合作记录，为社区提供成果。此外，与其他组织的互补努力的领导人定期举行会议，将确保该项目具有更广泛的相关性。

Understanding how genetic variation translates into phenotypic variation, and how this translation depends on the environment, is a major challenge for modern biology. It is fundamental to human genetics and agriculture, as well as evolutionary biology. Thanks to advances in technology, it is now possible to start answering this question by sequencing entire populations and connecting this information to phenotypic data, whether this be public health records, crop yield data, or the ability to withstand stress in a controlled experiment or in nature.There is, however, an important aspect that is often glossed over in all these (often highly publicized) efforts: we are still far from fully describing genetic variation on a population scale. The "next-generation" sequencing methods that have made it economically feasible to screen large numbers of individuals (the almost mythical "$1000 Human Genome") do not actually produce complete genome sequences - they produce massive numbers of very short sequence fragments that must be aligned to a reference genome in order to identify variants. Because of this, only simple variants (single nucleotide and very short insertion/deletion polymorphisms) are reported, and the results are invariably biased with respect to what is present or missing in the reference genome. Large or complex structural variants, as well as simple variants inside complex variants are generally missed completely. It is currently not known how serious this problem is, for the simple reason that finding out requires completely assembling large number of genomes, and comparing the result to data generated using standard methods. This is the objective of the 1001G+ proposal. Long-read sequencing has now advanced to a stage where generating nearly complete genomes for large samples is feasible - at least for organisms with relatively small genomes. Building on our success with the "1001 Genomes Project", we will assemble at least 50 genomes from a diverse collection of Arabidopsis thaliana strains, annotate them with transcriptome and epigenome information, and develop tools to make the results available to the community. This will go a long way toward answering the question of what is hidden in the part of the genome we currently cannot see - certainly in A. thaliana, but our results (and the tools and concepts we develop to find, interpret, and share complete information on sequence variants) will pave the way for similar studies in organisms with larger genomes, where the hidden part is likely to be relatively larger, and perhaps even more important.The project brings together a team of a researchers with complementary skills, considerable management expertise and a strong track record of collaborating to deliver results for the community. In addition, regular meetings with leaders of complementary efforts in other organisms will ensure the broader relevance of the project.