NHGRI/DIR Genomics Core

基因组学核心提供资源、服务和建议，以满足 NHGRI 研究人员与基因组学研究相关的需求。 Genomics Core 提供的基因分型服务被大量研究人员广泛使用。 去年，15 位调查员提出了超过 100 项请求。 大多数请求都是针对人类基因组 SNP 基因分型。 Core 使用 1M SNP 芯片处理了 50 个基因分型请求，总共 730 个 DNA 样本。还处理了多种其他 Illumina SNP 芯片（370K、550K、610K、1M Quad、2.5M Quad 和甲基化），使全年 SNP 基因型总数达到 8.5 亿。基因型主要用于使用高密度 SNP 芯片扫描基因组变化（缺失/重复/镶嵌），然而，这些数据可用于回答与连锁、关联、拷贝数和甲基化变化相关的各种其他问题。我们的研究人员利用基因型数据研究了多种疾病：多指症、小眼症、唇腭裂、前脑无裂畸形、未确诊疾病 (UDP)、戴蒙德-布莱克凡贫血、范可尼贫血、NF1 等。核心还继续提供基于 STRP 的基因分型。尽管有 40 多个 STRP 基因分型请求，但这些请求通常针对较少数量的样本。这些 STRP 基因分型服务涵盖了各种应用，例如扫描焦点区域以精细绘制连锁基因座、拷贝数变异、删除间隔的识别、删除起源的亲本以及小鼠研究（速度同源性、识别移植匹配、表型基因座）。一般来说，SNP 和 STRP 基因分型服务用于各种全基因组研究，包括探索甲基化状态。 虽然基因分型是核心在过去一年的主要活动，但也提供了有限的物理绘图和测序服务以及 DNA 面板的访问。核心资源中添加了一个新的 DNA 组：墨西哥裔美国人 (HD 100MEX)。我们继续提供来自人类、小鼠或斑马鱼文库的 BAC 克隆。测序服务仅限于运行研究者提供的反应板。 核心人员通过参加每个实验室的会议并征求他们的意见，完成了向 NHGRI 调查人员通报核心服务的计划。这些讨论富有成效，并有助于启动将核心可用的技术用于新颖的应用程序。例如，针对斑马鱼胚胎中锌指介导的诱变开发了一种快速有效的筛选策略。因此，核心致力于提高现有技术对新颖应用的利用。 Core 购买并安装了 Illumina iScan，它可以更快、更高效地扫描更新、更高密度的 Illumina SNP 芯片（2.5M 和 5M SNP）和高通量 (Omni_Express) SNP 芯片。先进的高密度技术允许每个芯片扫描多个样本，并且核心中配备了高效扫描仪，使得核心现在能够接受中等规模的基因分型项目并在合理的时间内完成它们。

The Genomics Core provides resources, services and advice to meet the needs of the NHGRI investigators related to genomics research. The genotyping services offered by the Genomics Core were used extensively and by a large number of investigators. In the past year, there were >100 requests by 15 investigators. The majority of requests were for human genome SNP genotyping. The Core processed 50 requests for genotyping with 1M SNP chips for a total of 730 DNA samples. A wide range of other Illumina SNP chips (370K, 550K, 610K, 1M Quad, 2.5M Quad and methylation) were processed, bringing the total to 850M SNP genotypes for the year. Genotypes were primarily used for scanning for genomic changes (deletions/duplications/mosaicism) using high density SNP chips, however, the data is useful for answering a variety of other questions related to linkage, association, copy number and methylation changes. Our investigators study a variety of disease conditions where the genotype data was utilized: Polydactyly, microphthalmia, cleft lip and palate, holoprosencephaly, undiagnosed diseases (UDP), Diamond-Blackfan anemia, Fanconi anemia, NF1 among others. The Core continues to provide STRP based genotyping as well. Although there were over 40 requests for STRP genotyping, these were typically for smaller number of samples. These STRP genotyping services covered a variety of applications, such as scanning focus regions for fine mapping of linked loci, copy number variation, identification of deletion intervals, parent of origin of deletions, and mouse studies (speed congenics, identifying transplant matches, loci for phenotypes). In general, the SNP and STRP genotyping services were used for a variety of genome-wide studies including exploring methylation status. While genotyping was the main activity of the Core for this past year, limited physical mapping and sequencing services, as well as access to DNA panels were also offered. A new DNA panel, Mexican-American (HD 100MEX), was added to the Core resources. We continue to provide access to BAC clones from human, mouse or zebrafish libraries. Sequencing services are limited to running the investigator provided reaction plates. Core personnel completed the initiative to inform NHGRI investigators about the Cores services through attending a meeting with each lab and sought their input. These discussions were productive and helped initiate utilization of the technologies available at the Core for novel applications. For instance, a quick and efficient screening strategy was developed for zinc-finger mediated mutagenesis in zebrafish embryos. Thus, the Core strives to enhance the utilization of available technologies for novel applications. The Core purchased and installed an Illumina iScan which allows faster, more efficient scanning of newer, higher density Illumina SNP chips (2.5M, and 5M SNPs) and the high throughput (Omni_Express) SNP chips. Advancing high-density technologies, which allows scanning multiple samples per chip, and availability in the Core of an efficient scanner, permits the Core now to accept moderately large genotyping projects and complete them in a reasonable length of time.