Telomere-to-telomere assemblies of human genomes

人类基因组的端粒到端粒组装

基本信息

批准号：
10670902
负责人：
Karen Hayden Miga
金额：
$ 74.91万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-14 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10670902
关键词：
Address Benchmarking Biological Assay Biomedical Research Cell Line Cells Centromere Chromosomes Collection Communities Complete Hydatidiform Moles Data Diploidy Disease Ensure Equipment Evaluation Funding Gel Genetic Variation Genome Genome Stability Genomics Haploidy Haplotypes Health Hour Human Human Chromosomes Human Genome Individual Informatics Infrastructure Length Manuals Maps Measures Methods Molecular Optics Phase Physiologic pulse Production Repetitive Sequence Research Resolution Source Structure Techniques Technology Testing United States National Institutes of Health Validation Variant Work arm base cloud based cohort computerized data processing cost cost effective design human pangenome human reference genome improved innovation nanopore novel novel strategies reference genome success technological innovation telomere whole genome

项目摘要

Project Summary Approaches to complete the human genome will benefit from careful, benchmarked advances that demonstrate the capability to fully assemble and phase diploid chromosomes. The remaining unresolved regions in our high- resolution genomic maps are known to contain long tracts of repeats. The long-term objective of our research is to develop new experimental methods to complete chromosome scale assemblies to study the sequence organization, structural diversity, and disease impact of these novel sequences. In our first aim, we demonstrate the use of new approaches to generate the first telomere-to-telomere phased assembly of a human genome using effectively haploid complete hydatidiform moles (CHMs), and demonstrate the ability to scale these methods to a panel of CHMs. In our second aim we focus on validation methods of repeat assemblies to improve upon the structural and base-level accuracy of our assemblies. In our third aim we harden haplotype phasing method using high coverage ultra long data from diploid genomes to guide phased chromosome assemblies. We propose to optimize a new, cost-effective method of improving high quality reference genomes to reach complete, telomere-to-telomere genome assemblies. This research has the additional benefit that it will add new sequence to the human genome to systematically explore genetic variation of regions frequently overlooked as part of disease association and functional studies.

项目概要完成人类基因组的方法将受益于仔细的、基准化的进展，这些进展表明完全组装和定相二倍体染色体的能力。我们的高水平中剩余的未解决的区域已知分辨率基因组图谱包含长段重复序列。我们研究的长期目标是开发新的实验方法来完成染色体规模组装以研究序列这些新序列的组织、结构多样性和疾病影响。在我们的第一个目标中，我们展示使用新方法生成人类基因组的第一个端粒到端粒的分阶段组装使用有效的单倍体完整葡萄胎（CHM），并证明了扩展这些葡萄胎的能力 CHM 小组的方法。在我们的第二个目标中，我们重点关注重复装配的验证方法，以改进基于我们组件的结构和基准精度。在我们的第三个目标中，我们强化单倍型定相使用来自二倍体基因组的高覆盖超长数据来指导定相染色体组装的方法。我们建议优化一种新的、具有成本效益的方法来提高高质量参考基因组，以达到完整的端粒到端粒基因组组装。这项研究还有一个额外的好处，那就是它会增加新的人类基因组序列，系统地探索经常被忽视的区域的遗传变异疾病关联和功能研究的一部分。