HIGH QUALITY HUMAN AND NON-HUMAN PRIMATE GENOME ASSEMBLIES

高品质人类和非人类灵长类动物基因组组装

• 批准号: 9132558
• 负责人: SUSAN K DUTCHER
• 金额: $ 164.42万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-03 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9132558
• 关键词: Cell Line; Chromosomes; Collection; Communities; Complementary DNA; Complex; Consensus; Data; Data Set; Disease; Evolution; Gene Expression Regulation; Genes; Genetic Predisposition to Disease; Genetic Variation; Genome; Genomic Library; Genomics; Goals; Haplotypes; Hereditary Disease; Human; Human Genetics; Human Genome; Individual; Lead; Length; Libraries; Maps; Methods; Modeling; Phase; Phylogeny; Population Heterogeneity; Primates; Production; Reading; Reference Standards; Research; Research Personnel; Research Project Grants; Resolution; Resources; Sampling; Structure; Technology; Time; Tissues; Transcript; Variant; Work; base; genetic resource; genome annotation; genome browser; human disease; human genome sequencing; human reference genome; improved; indexing; induced pluripotent stem cell; interest; meetings; mouse genome; nonhuman primate; public health relevance; reference genome; scaffold; single molecule; time use; transcriptome sequencing

 DESCRIPTION (provided by applicant): A collection of diverse and highly accurate primate genomes are critical to further our understanding of human variation and the evolutionary context of genetic disease. The main goal of this proposal is to generate high quality reference genomes that better represent the complexity of human diversity (i.e., continental human reference genomes) and that significantly improve the quality of index non-human primate (NHP) genomes, reaching a quality level more in line with the current human genome (GRCh38). We have selected 8 human genomes and 8 NHP for de novo sequencing and assembly using single molecule real-time sequencing followed by extensive higher-level resolution using experimental approaches. The end-result will be a set of NHP genomes that represent a >10-20 fold improvement in assembly continuity and representation of each and human genomes where >95% of euchromatic unique regions are fully sequenced, annotated, and phased. This project includes a special emphasis on gaps and gene-rich complex sequence structure, which have been the most intractable euchromatic regions of primate genomes. While there are many metrics of genome assembly completion and sequencing, ours is a practical one. The goal of this project is complete euchromatic sequence where >95% of the bases are ordered and oriented, and >95% of gene models are complete and annotated. Assemblies based on improved genome scaffolding or simple phasing of short read data using synthetic long reads add value but do not meet the needs of most researchers who are interested in studying gene models, gene regulation, and genetic variation. The community requires that sequence gaps are resolved and each genome is assembled at high contiguity. Our strategy is to deliver quality over quantity, and as such we are focused on a smaller subset of genomes delivered at the highest quality, building upon very recent advances in sequencing technology and assembly.

 描述（由适用提供）：多样性和高度准确的灵长类动物基因组的集合对于进一步了解人类变异和遗传疾病的进化环境至关重要。该提案的主要目标是产生高质量的参考基因组，更好地代表人类多样性的复杂性（即大陆人类参考基因组），并显着提高索引非人类灵长类动物（NHP）基因组的质量，与当前的人类基因组（GRCH38）更加一致。我们选择了8个人类基因组和8个NHP进行从头测序和组装，并使用单分子实时测序，然后使用实验方法进行广泛的高级分辨率。最终结果将是一组NHP基因组，代表> 10-20倍的组装连续性以及每个和人类基因组的表示，其中> 95％的构想独特区域中的95％是完全测序，注释和分阶段的。该项目包括对差距和富基因的复合序列结构的特别强调，这些序列结构是原代基因组中最棘手的正式区域。尽管基因组组装完成和测序有许多指标，但我们的基因组组装完成和测序是实用的。该项目的目的是完整的构想序列，其中> 95％的碱基被排序和定向，> 95％的基因模型已完成和注释。基于改进的基因组脚手架或使用合成的长读数对简短读取数据进行改进的组件增加了价值，但不能满足大多数有兴趣研究基因模型，基因调节和遗传变异的研究人员的需求。社区要求序列间隙得到解决，每个基因组都以高连续性组装。我们的策略是提供质量而不是数量，因此，我们专注于以最高质量传递的较小基因组，这是基于测序技术和组装的最新进展。