Center for Human Reference Genome Diversity

项目摘要 我们的人类参考基因组多样性中心的目标是产生无错误，无间隙，完整， 和正确的单倍型定相的基因组组装尽可能从一组350人全面 捕捉人类多样性的全部。我们的目标是捕获>99%的等位基因变体，其中>1%的等位基因 频率，并将这些基因组作为资源提供给国际社会， 医学和研究，解决生物学和疾病的基本未回答的问题。我们会委聘 多平台的方法，使用尖端的长读和链接读技术，以获得最高的 高质量的基因组目标1将集中于样本收集和采购细胞系从至少350 特别强调填补人类多样性的空白。目标2将产生高度连续的 染色体水平的组装，超过99%的单倍型定相的至少700个单倍体基因组从350 二倍体样品目标3将完成这些基因组，使其从端粒到端粒（T2T）都是无间隙的， 染色体目标4将评估基因组的准确性和完整性，并进行初始变异 呼吁评估人类多样性的水平。我们将使用一种新的技术组合， 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 迄今为止的基因组组装。我们的努力将具体针对被其他努力排除在外的区域， 包括节段复制、着丝粒和近端着丝粒DNA。为了实现这些目标，我们 组建了一个由来自世界各地的同意伦理领导者组成的特殊团队，样本 收集、样本提取、高质量基因组测序、组装、整理和评估。的 该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， 高度认识到使用该资源的生物医学研究人员的实际需求。高质量 产生的基因组将被传递到人类参考基因组中心（HGRC）和基因组参考 用于策展和发布的表示（GRR）组。其结果将是一个泛人类基因组参考， 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 染色体水平和揭示一个更准确和全球的人口观。

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.