CORE--MOLECULAR GENETICS CORE

核心--分子遗传学核心

• 批准号: 7670393
• 负责人: BEVERLY S EMANUEL
• 金额: $ 25.53万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670393
• 关键词: Abnormal Cell; Affect; Algorithms; Alleles; Area; Base Pair Mismatch; Binding; Biological Assay; Candidate Disease Gene; Capillary Electrophoresis; Cells; Characteristics; Chemistry; Chromosome Mapping; Chromosomes; Code; Color; Complex; Computer software; Condition; Core Facility; DNA; DNA Resequencing; DNA Sequence; DNA analysis; Data; Data Collection; Detection; Development; Diagnostic; Discrimination; Disease; Environment; Equipment; Gel; Gene Dosage; Gene Expression; Gene Family; Generations; Genes; Genetic; Genome; Genomics; Genotype; Hereditary Disease; Individual; Inheritance Patterns; Label; Laboratories; Lead; Length; Ligation; Maps; Measurement; Mental Retardation and Developmental Disabilities Research Centers; Messenger RNA; Methodology; Methods; Microsatellite Repeats; Molecular Biology; Molecular Genetics; Molecular Medicine; Molecular Profiling; Mutation; Mutation Detection; Nature; Numbers; Oligonucleotides; Output; Pattern; Personal Satisfaction; Pliability; Polymerase Chain Reaction; Population; Positioning Attribute; Preparation; Primer Extension; Product Labeling; Proteins; RNA; Reaction; Reagent; Relative (related person); Reproducibility; Research Personnel; Resources; Role; Running; Sampling; Scanning; Schedule; Scheme; Score; Series; Services; Signal Transduction; Single Nucleotide Polymorphism; Single Nucleotide Polymorphism Map; Site; Solid; Source; Staging; Staining method; Stains; Standards of Weights and Measures; Structure; Surface; System; Tail; Technical Expertise; Technology; Temperature; Time; Transcript; Zip Code; base; cellular imaging; cost; cyanine; day; density; design; desire; gene discovery; gene function; genetic analysis; inhibitor/antagonist; insertion/deletion mutation; new technology; protein function; research study; tool

As with other areas of molecular medicine, the study of underlying causes for MRDD has reached a level of complexity that will require powerful new tools to identify gene families, to map their coordinated expression and to understand how regulatory mechanisms are disrupted by disease. In the continuing commitment to support the investigators of the MRDDRC, the Molecular Genetics Core Facility has expanded its equipment and services to include those that will make the complex studies described above feasible. We have fine-tuned our other services so that they are routine, cost-effective and highly successful with rapid turnaround times. We will now focus on implementing new technologies, including high-throughput genotyping and microarrays to facilitate the study of gene expression patterns in normal and affected individuals. Some genetic diseases occur as the result of changes in DNA sequence or larger regions of genes or chromosomes, leading to missing or abnormal functioning of proteins and other gene products. However, some diseases may result from normal gene products that are expressed at abnormal levels, at inappropriate times in cell development or other more subtle aberrations. A promising approach to discovering how genes function and interact to produce normal and disease states is comparison of mRNA profiles from normal and abnormal cells or from cells at different stages of development. The altered pattern of expression that is observed may lead to identification of the roles of certain genes or could even be diagnostic for a particular disease. Ultimately the understanding of these gene systems may lead to more specific rationale-based therapies for a given disease. Parallel analyses of expression profiles on microdevices facilitates gene expression studies in several ways. First, the analysis of the complex population of cellular RNAs is well suited to the highthroughput parallel approach that microarrays provide. Such microdevices would also make efficient use of the limited amount of precious RNA isolated from cells as well as of the specialized reagents for amplification and detection. The increase in throughput and sensitivity combined with decreased cost per sample should make it possible to conduct experiments which will maximize the likelihood of detecting changes in these profiles while permitting numerous manipulations of variables and treatments. In addition to expression profiling, microarrays can be used to screen for one or numerous mutations in many individuals, determination of gene copy number and gene mapping studies. Quantitative PCR will also have a variety of applications to the projects in the Center, including relative and absolute transcript analysis and mutation detection.

与分子医学的其他领域一样，对MRDD潜在原因的研究已经达到了 这将需要强大的新工具来识别基因家族，绘制其协调表达图 并了解疾病是如何扰乱调控机制的。在继续致力于 支持MRDDRC的研究人员，分子遗传学核心设施扩大了其设备 和服务，以包括那些将使上述复杂研究可行的服务。我们已经微调了 我们的其他服务使它们成为常规的、成本效益高且非常成功的服务，周转时间很快。我们 现在将专注于实施新技术，包括高通量基因分型和微阵列 促进研究正常和受影响个体的基因表达模式。 一些遗传性疾病是由于DNA序列或更大的基因区域或 染色体，导致蛋白质和其他基因产物功能缺失或不正常。然而，一些人 疾病可能是由于正常的基因产物在不适当的时间以异常的水平表达 细胞发育或其他更微妙的异常。发现基因功能的一种很有前途的方法 而相互作用产生正常和疾病状态是正常和异常的mRNA图谱的比较 细胞或来自不同发育阶段的细胞。观察到的改变的表达模式可以 导致确定某些基因的作用，甚至可能对特定疾病进行诊断。 最终，对这些基因系统的了解可能会导致更具体的基于理论基础的治疗方法 考虑到疾病。微设备上表达谱的并行分析促进了基因表达研究 有好几种方法。首先，对复杂的细胞RNA群体的分析非常适合于高通量 微阵列提供的并行方法。这样的微型设备还将有效地利用 有限数量的从细胞中分离的珍贵RNA以及用于扩增和 侦测。产量和灵敏度的提高，加上每份样品成本的降低，应该会使它 可以进行实验，最大限度地检测到这些配置文件中的变化，同时 允许对变量和处理进行多次操作。除了表达特征外， 微阵列可用于在许多个体中筛选一个或多个突变、确定基因 拷贝数和基因作图研究。定量聚合酶链式反应也将在许多方面得到应用 该中心的项目，包括相对和绝对转录分析和突变检测。