NHGRI/DIR Genomics Core

Illumina和ABI技术都被许多研究人员广泛使用。在2023财年，除了两个项目(NISC和UDP)外，共有八名NHGRI调查人员，代表七个分支机构/办事处，使用了Core基因分型服务。在NHGRI之外，来自其他研究所(NCI、NHLBI和NIMH)的四名研究人员今年也利用了核心服务。在过去四年，即2020-2023财年，核心处理的DNA样本数目分别为6,407、7,556、8,243和5,425个。在2023财年，Core产生了39.3亿个(B)基因型，而在2021财年和2022财年，核心分别产生了3.25B和4.55B。请注意，除了STRP之外，这个数字还代表给定阵列上的SNP总数乘以该阵列运行的样本数量(例如，对10个样本运行的100万个SNP阵列代表1000万个基因类型)，并跟踪数据。 基因分型数据用于与钻石-黑粉贫血、Fanconi贫血、癌症、遗传性骨髓衰竭综合征、Smith-Magenis综合征、急性髓系白血病、ADHD、先天性心脏病、肾脏疾病、眼皮肤白化病和遗传性软骨瘤病等相关的研究。通过血统、拷贝数变化、缺失间隔、甲基化状态、缺失的父母来源、嵌合体，并生成单倍型，以从序列数据中发现变异。 除了许多小项目外，核心还有以苏格兰民族党为基础的大型项目。在过去三年(2021财年至2023财年)，核心为NISC处理的样本数量分别为1,824、2,688和2,112。为NISC处理的基因分型样本属于来自其他研究所的多名研究人员，这表明基因组学核心服务于更大的科学界，而不仅仅是NHGRI。2018财年，完成了由5,056个和4,118个DNA样本组成的两个大型SNP基因分型项目。 在SNP阵列上运行的样本(3,744个样本)约占CORE今年处理的5,425个DNA样本的69%，高于过去两年的百分比(55%和61%)。这反映了人们对SNP基因分型技术的持续兴趣。其余31%的样本是使用ABI技术处理的，主要是小鼠DNA样本。CRISPR突变技术正在扩展到越来越多的小鼠突变项目。 核心还协助调查人员进行数据分析和访问软件/工具，如GoldenHelix、Nexus和GenomeStudio。核心帮助研究人员利用学习和使用这些工具以及任何相关开源软件的优势，并帮助处理、收集、评估和处理SNP和其他数据集。此外，核心还帮助排除和解决调查人员在处理数据和执行质量控制评估时可能遇到的问题。这项服务对小型项目的调查人员具有巨大的价值，核心的大多数用户也是如此，他们缺乏分析大型数据集所需的工具或专业知识。此外，还为几项研究提供了重要的数据分析支持。例如，为了对352名OCA患者进行分子诊断，并编制OCA导致变异的全面目录，从被诊断为眼皮肤白化病1B型的个体收集DNA样本，用全基因组SNP阵列分析染色体拷贝数变异。三个人被发现有TYR缺失(Loftus等人，基于单倍型的分析解决了眼皮肤白化病1B型缺失的遗传性。《美国人类遗传学杂志2023》)。

Both Illumina and ABI technologies are widely used by many investigators. This year, FY2023, in addition to two programs (NISC and UDP), a total of eight NHGRI investigators, representing seven branches/offices, used the Core genotyping services. Outside of NHGRI, four investigators from other institutes (NCI, NHLBI and NIMH) also utilized the Cores services this year. Over the past four years, FY2020-FY2023, the number of DNA samples processed by the Core were 6,407, 7,556, 8,243 and 5,425 respectively. The Core generated 3.93 billion (B) genotypes in FY2023, compared to 3.25 B and 4.55 B in FY2021 and FY2022, respectively. Please note, in addition to STRPs, this number represents the total number of SNPs on a given array multiplied by the number of samples for which that array was run (e.g., a one million SNP array run on 10 samples represents 10 million genotypes) and data was tracked. The genotyping data is used for studies related to Diamond-Blackfan anemia, Fanconi anemia, cancer, inherited bone marrow failure syndromes, Smith-Magenis syndrome, acute myeloid leukemia, ADHD, congenital heart disease, kidney disease, oculocutaneous albinism, and genochondromatosis, etc. The data are analyzed for identity by descent, copy number variation, deletion intervals, methylation status, parent-of-origin of deletions, mosaicism, and to generate haplotypes for discovering variants from sequence data. In addition to numerous small projects, the Core has large SNP-based projects. Over the last three years (FY2021 - FY2023), the number of samples the Core processed for NISC were 1,824, 2,688, and 2,112 respectively. The genotyping samples processed for NISC belong to multiple investigators from other institutes, demonstrating that the Genomics Core serves a larger scientific community than just NHGRI. In FY2018, two large SNP genotyping projects consisting of 5,056 and 4,118 DNA samples were completed. Samples run on SNP arrays (3,744 samples) represent about 69% of the total 5,425 DNA samples processed by the Core this year, which is a higher percentage than the last two years (55% and 61%). This reflects continued interest in the use of SNP genotyping technologies. The remaining 31% of samples were processed using ABI technology, primarily mouse DNA samples. The CRISPR mutagenesis technology is being extended to an increasing number of mouse mutagenesis projects. The Core also assists investigators with data analysis and access to software/tools, such as GoldenHelix, Nexus, and GenomeStudio. The Core helps researchers take advantage of learning and using these tools, and any relevant open-source software, and helps with the handling, collection, evaluation, and processing of SNP and other data sets. In addition, the Core also helps with troubleshooting and problem-solving issues investigators may have in handling their data and performing QC assessments. This service is of huge value to investigators with small projects, as are most users of the Core, who lack the required tools or expertise for the analysis of large data sets. In addition, significant data analysis support is given for several studies. As an example, in an effort to molecularly diagnose a cohort of 352 OCA patients and compile a comprehensive catalog of OCA-causing variants, DNA samples collected from individuals diagnosed with oculocutaneous albinism type 1B were analyzed by genome-wide SNP array for chromosomal copy number variations. Three individuals were found to have deletions of TYR (Loftus et al., Haplotype-based analysis resolves missing heritability in oculocutaneous albinism type 1B. American Journal of Human Genetics 2023).