Center for Human Reference Genome Diversity

项目摘要 我们人类参考基因组多样性中心的目标是产生无错误、无缝隙、完整 并从一组350人中尽可能正确地进行单倍型-阶段基因组组装 捕捉到人类多样性的全部范围。我们的目标是捕获99%的等位基因变异和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，以使基因组 解决生物学和疾病中尚未回答的基本问题的医学和研究。我们将聘用 使用尖端长读和链接阅读技术的多平台方法，以获得最高 优质的阶段性基因组。AIM 1将专注于从至少350个细胞系中收集样本和获取细胞系 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 来自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合超过99%的单倍型阶段性 二倍体样本。目标3将完成这些基因组从端粒到端粒(T2T)的无缝连接 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，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 基因组组装到目前为止。我们的努力将专门针对那些被其他努力排除在外的地区， 包括片段复制、着丝粒和顶端着丝粒DNA。为了实现这些目标，我们有 组建了一个由来自世界各地的同意伦理领域的领导人组成的非凡团队，样本 采集、样本提取，以及高质量的基因组测序、组装、整理和评估。这个 团队在使用基因组技术解决广泛的科学问题方面也有专业知识，所以 高度了解将使用这一资源的生物医学研究人员的实际需求。高品质的 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 管理和放行的代表(GRR)小组。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没有的重要的人类多样性。我们生成的数据将 使人类遗传学发生根本性转变，促进新发现从单核苷酸到 染色体水平，并揭示了更准确和全球的人类人口观点。

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.