Geisert Eldon E, Lu Lu, Freeman-Anderson Natalie E, Templeton Justin P, Nassr Mohamed, Wang Xusheng, Gu Weikuan, Jiao Yan, Williams Robert W
Department of Ophthalmology and Center for Vision Research, Memphis, TN 38163, USA.
Mol Vis. 2009 Aug 31;15:1730-63.
Individual differences in patterns of gene expression account for much of the diversity of ocular phenotypes and variation in disease risk. We examined the causes of expression differences, and in their linkage to sequence variants, functional differences, and ocular pathophysiology.
mRNAs from young adult eyes were hybridized to oligomer microarrays (Affymetrix M430v2). Data were embedded in GeneNetwork with millions of single nucleotide polymorphisms, custom array annotation, and information on complementary cellular, functional, and behavioral traits. The data include male and female samples from 28 common strains, 68 BXD recombinant inbred lines, as well as several mutants and knockouts.
We provide a fully integrated resource to map, graph, analyze, and test causes and correlations of differences in gene expression in the eye. Covariance in mRNA expression can be used to infer gene function, extract signatures for different cells or tissues, to define molecular networks, and to map quantitative trait loci that produce expression differences. These data can also be used to connect disease phenotypes with sequence variants. We demonstrate that variation in rhodopsin expression efficiently predicts candidate genes for eight uncloned retinal diseases, including WDR17 for the human RP29 locus.
The high level of strain variation in gene expression is a powerful tool that can be used to explore and test molecular networks underlying variation in structure, function, and disease susceptibility. The integration of these data into GeneNetwork provides users with a workbench to test linkages between sequence differences and eye structure and function.
基因表达模式的个体差异是眼部表型多样性和疾病风险变异的主要原因。我们研究了表达差异的原因，以及它们与序列变异、功能差异和眼部病理生理学的联系。
将成年幼体眼睛的mRNA与寡聚物微阵列（Affymetrix M430v2）杂交。数据被嵌入到基因网络中，该网络包含数百万个单核苷酸多态性、定制阵列注释以及互补的细胞、功能和行为特征信息。数据包括来自28个常见品系、68个BXD重组近交系的雄性和雌性样本，以及几个突变体和基因敲除样本。
我们提供了一个完全整合的资源，用于绘制、图示、分析和测试眼睛中基因表达差异的原因和相关性。mRNA表达的协方差可用于推断基因功能、提取不同细胞或组织的特征、定义分子网络以及绘制产生表达差异的数量性状位点。这些数据还可用于将疾病表型与序列变异联系起来。我们证明视紫红质表达的变异有效地预测了八种未克隆视网膜疾病的候选基因，包括人类RP29位点的WDR17。
基因表达中高水平的品系变异是一种强大的工具，可用于探索和测试结构、功能和疾病易感性变异背后的分子网络。将这些数据整合到基因网络中为用户提供了一个测试序列差异与眼睛结构和功能之间联系的工作台。
