Center for Human Reference Genome Diversity

人类参考基因组多样性中心

基本信息

批准号：
10686965
负责人：
Evan Eichler
金额：
$ 398.92万
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：
2019
资助国家：
美国
起止时间：
2019-09-18 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10686965
关键词：
Address Algorithms Attention Biology Blood specimen Budgets Callback Cell Line Centromere Chromosomes Code Collection Communities Complex Consent Country DNA Data Diploidy Disease Ensure Ethics Evaluation Exclusion Feedback Fostering Future Gene Frequency Genetic Diseases Genetic Variation Genome Genomic medicine Genomics Goals Haploidy Haplotypes Health Human Human Genetics Human Genome Human Resources Individual Informatics Information Dissemination Informed Consent International Link Manuals Medical center Methods National Human Genome Research Institute New York Nucleotides Patients Persons Phase Population Production Protocols documentation Repetitive Sequence Research Research Personnel Resources Sample Size Sampling Technology Third Generation Sequencing Time Validation Variant Work biobank cloud platform cohort computerized data processing cost data repository data sharing design genetic variant genome sequencing human pangenome human reference genome improved lymphoblastoid cell line new technology novel outreach pan-genome prevent programs reference genome sample collection scaffold telomere vertebrate genome

项目摘要

Project Abstract The goal of our Center for Human Reference Genome Diversity is to generate as error-free, gapless, complete, and correctly haplotype-phased genome assemblies as possible from a set of 350 persons comprehensively capturing the full extent of human diversity. We aim to capture >99% of allelic variants with >1% allele frequency, and to provide these genomes as a resource to the international community to enable genomic medicine and research addressing fundamental unanswered questions in biology and disease. We will employ a multi-platform approach using cutting-edge long read and linked read technologies to obtain the highest quality phased genomes. Aim 1 will focus on sample collection and procuring cell lines from at least 350 individuals with a specific emphasis on filling in gaps in human diversity. Aim 2 will generate highly contiguous chromosomal level assemblies that are over 99% haplotype-phased for at least 700 haploid genomes from 350 diploid samples. Aim 3 will finish these genomes to be gapless from telomere-to-telomere (T2T) for each chromosome. Aim 4 will evaluate the genomes for accuracy and completeness and perform initial variant calling to assess the level of human diversity. We will use a novel combination of technologies, sequencing strategies, and algorithms that we and others developed to produce the highest quality and most complete genome assemblies to date. Our effort will specifically target regions that have been excluded by other efforts, including segmental duplications, centromeres, and acrocentric DNA. To achieve these aims we have assembled an exceptional team consisting of leaders from around the world in consent ethics, sample collection, sample extraction, and high-quality genome sequencing, assembly, finishing and evaluation. The team also has expertise in using genomic technologies to address a broad range of scientific questions, so is highly cognizant of the practical needs of biomedical researchers who will use this resource. The high-quality genomes produced will be passed to the Human Reference Genome Center (HGRC) and Genome Reference Representation (GRR) groups for curation and release. The result will be a pan-human genome reference, representing important human diversity not present in the current reference genome. The data we generate will enable a fundamental shift in human genetics, fostering new discoveries from the single-nucleotide to chromosomal levels and revealing a more accurate and global view of the human population.

项目摘要我们人类参考基因组多样性中心的目标是生成无错误、无间隙、完整、并尽可能从 350 人的集合中进行正确的单倍型定相基因组组装捕捉人类多样性的全部范围。我们的目标是捕获 >99% 的等位基因变异（等位基因 >1%）频率，并将这些基因组作为资源提供给国际社会，以使基因组医学和研究解决生物学和疾病中尚未解答的基本问题。我们将聘用使用尖端的长读和链接读技术的多平台方法以获得最高的质量定相基因组。目标 1 将重点关注样本采集和至少 350 个细胞系的采购特别强调填补人类多样性空白的个人。目标 2 将生成高度连续的 350 个单倍体基因组中至少 700 个单倍体基因组的染色体水平组装超过 99% 二倍体样品。目标 3 将完成这些基因组，使每个基因组从端粒到端粒 (T2T) 都无间隙。染色体。目标 4 将评估基因组的准确性和完整性并执行初始变异呼吁评估人类多样性的水平。我们将使用一种新颖的技术组合，测序我们和其他人开发的策略和算法，以产生最高质量和最完整的结果迄今为止的基因组组装。我们的努力将专门针对被其他努力排除在外的地区，包括片段重复、着丝粒和近端着丝粒 DNA。为了实现这些目标，我们有组建了一支由来自世界各地同意道德领域的领导者组成的杰出团队，样本采集、样本提取以及高质量基因组测序、组装、整理和评估。这团队还拥有使用基因组技术解决广泛科学问题的专业知识，因此高度认识到将使用该资源的生物医学研究人员的实际需求。高品质产生的基因组将传递给人类参考基因组中心（HGRC）和基因组参考用于管理和发布的代表 (GRR) 团体。结果将成为泛人类基因组参考，代表了当前参考基因组中不存在的重要人类多样性。我们生成的数据将使人类遗传学发生根本性转变，促进从单核苷酸到染色体水平并揭示对人类群体的更准确和全球性的看法。