NHGRI/DIR Genomics Core

NHGRI/DIR 基因组学核心

• 批准号: 10920225
• 负责人: settara chandrasekharappa
• 金额: $ 152.52万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10920225
• 关键词: Acute Myelocytic Leukemia; American; Attention deficit hyperactivity disorder; Bacterial Artificial Chromosomes; Blood capillaries; CRISPR/Cas technology; Catalogs; Clustered Regularly Interspaced Short Palindromic Repeats; Collection; Communication; Communities; Complement; Computer software; Consultations; Copy Number Polymorphism; DNA; Data; Data Analyses; Data Set; Diagnosis; Diamond-Blackfan anemia; Evaluation; Fanconi' s Anemia; Genetic; Genome; Genomic Segment; Genomics; Genotype; Haplotypes; Heritability; Human; Human Cell Line; Human Genetics; Individual; Inherited; Journals; Kidney Diseases; Learning; Ligation; Malignant Neoplasms; Methylation; Molecular Diagnosis; Mosaicism; Mus; Mutagenesis; National Heart, Lung, and Blood Institute; National Human Genome Research Institute; National Institute of Mental Health; Oculocutaneous Albinism; Parents; Patients; Problem Solving; Process; Research; Research Personnel; Resources; Running; SNP array; SNP genotyping; Sampling; Services; Smith Magenis syndrome; Speed; Technology; Testing; United States National Institutes of Health; Update; Variant; Zebrafish; bead chip; bone marrow failure syndrome; cohort; congenic; congenital heart disorder; data access; design; genome-wide; genotyping technology; identity by descent; insertion/deletion mutation; interest; large datasets; meetings; mutation screening; open source; programs; research study; tool; zinc finger nuclease technology

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).

Illumina和ABI技术都被许多研究人员广泛使用。今年，2023财年，除了两个项目（NISC和UDP）外，共有八名NHGRI研究员（代表七个分支机构/办事处）使用了核心基因分型服务。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使用了Cores服务。在过去四年（2020财政年度至2023财政年度），核心中心处理的DNA样本数目分别为6，407、7，556、8，243及5，425。Core在2023财年产生了39. 3亿个（B）基因型，而2021财年和2022财年分别为3. 25个B和4. 55个B。请注意，除了STRP之外，该数字还表示给定阵列上的SNP总数乘以该阵列运行的样品数量（例如，在10个样品上运行的100万个SNP阵列代表1000万个基因型）并跟踪数据。 基因分型数据用于与Diamond-Blackfan贫血、Fanconi贫血、癌症、遗传性骨髓衰竭综合征、Smith-Magenis综合征、急性髓性白血病、ADHD、先天性心脏病、肾脏疾病、眼皮肤白化病和基因软骨瘤病等相关的研究。以及产生用于从序列数据中发现变体的单体型。 除了众多的小项目外，Core还有基于SNP的大型项目。过去三年（2021财政年度至2023财政年度），Core为NISC处理的样本数量分别为1，824、2，688及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。于2018财政年度，完成了两个大型SNP基因分型项目，分别包括5，056份及4，118份DNA样本。 在SNP阵列上运行的样本（3，744个样本）约占今年核心处理的5，425个DNA样本的69%，这比过去两年（55%和61%）更高。这反映了对SNP基因分型技术的持续兴趣。其余31%的样本使用ABI技术处理，主要是小鼠DNA样本。CRISPR诱变技术正在扩展到越来越多的小鼠诱变项目中。 Core还协助研究人员进行数据分析和访问软件/工具，如GoldenHacker、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的开源软件，并帮助处理，收集，评估和处理SNP和其他数据集。此外，核心还有助于故障排除和解决问题的研究人员可能在处理他们的数据和执行质量控制评估。这项服务对于小项目的调查人员和核心数据库的大多数用户都具有巨大价值，因为他们缺乏分析大型数据集所需的工具或专门知识。此外，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一份全面的OCA致病变异体目录，从诊断为1B型眼皮肤白化病的个体中收集的DNA样本通过全基因组SNP阵列分析染色体拷贝数变异。发现三个个体具有TYR缺失（洛夫图斯等人，基于单体型的分析解决了眼皮肤白化病1B型缺失的遗传力美国人类遗传学杂志2023）。