CORE--MOLECULAR GENETICS CORE

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 复杂性将需要强大的新工具来识别基因家族，绘制它们的协调表达图， 并了解疾病是如何破坏调节机制的。在继续致力于 为了支持MRDDRC的研究人员，分子遗传学核心设施扩大了其设备 和服务，包括那些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，使他们是例行的，具有成本效益和高度成功的快速周转时间。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， 有助于研究正常和受影响个体的基因表达模式。 一些遗传性疾病的发生是由于DNA序列或更大的基因区域的变化， 染色体，导致蛋白质和其他基因产物的缺失或异常功能。但也有 疾病可能是由正常基因产物在不适当的时间以异常水平表达引起的。 细胞发育或其他更微妙的畸变。发现基因功能的一种有希望的方法 并相互作用产生正常和疾病状态的是比较正常和异常的mRNA谱 细胞或来自不同发育阶段的细胞。观察到的表达模式改变可能 从而确定某些基因的作用，甚至可以诊断特定的疾病。 最终，对这些基因系统的理解可能会导致更具体的基于合理性的治疗方法， 鉴于疾病。微设备上表达谱的并行分析促进了基因表达研究 几种方式。首先，细胞RNA的复杂群体的分析非常适合于高通量分析。 微阵列提供的并行方法。这样的微器件也将有效地利用 有限量的从细胞中分离的珍贵RNA以及用于扩增的专用试剂， 侦测通量和灵敏度的提高，加上每个样品成本的降低， 有可能进行实验，这将最大限度地提高检测这些配置文件中的变化的可能性， 允许对变量和处理进行多种操作。除了表达谱分析， 微阵列可用于在许多个体中筛选一个或多个突变，确定基因突变， 拷贝数和基因定位研究。定量PCR也将具有多种应用于 该中心的项目，包括相对和绝对转录分析和突变检测。

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.