Lu Ye, Zhou Diana, King Rebecca, Zhu Shuang, Simpson Claire L, Jones Byron C, Zhang Wenbo, Geisert Eldon E, Lu Lu
Department of Ophthalmology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China.
Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN.
Mol Vis. 2018 Feb 2;24:115-126. eCollection 2018.
Usher syndrome (US) is characterized by a loss of vision due to retinitis pigmentosa (RP) and deafness. US has three clinical subtypes, but even within each subtype, the severity varies. Myosin VIIA, coded by , has been identified as one of the causal genes of US. This study aims to identify pathways and other genes through which interacts to affect the presentation of US symptoms.
In this study, we used the retinal tissue of BXD recombinant inbred (RI) mice to examine the expression of and perform genetic mapping. Expression quantitative trait locus (eQTL), single nucleotide polymorphism (SNP), and gene correlation analysis were performed using GeneNetwork. Gene set enrichment analysis was performed using WebGestalt, and gene network construction was performed using the Gene Cohesion Analysis Tool.
We found to be -regulated, with varied levels of expression across BXD strains. Here, we propose a genetic network with 40 genes whose expression is highly correlated with . Among these genes, six have been linked to retinal diseases, three to deafness, and five share a transcription factor with Gene ontology and pathway analysis revealed a strong connection among ion channel activity, , and US.
Although is a causal gene of US type I, this gene works with many other genes and pathways to affect the severity of US. Many of the genes found in the genetic network, pathways, and gene ontology categories of are related to either deafness or blindness. Further investigation is needed to examine the specific relationships between these genes, which may assist in the treatment of US.
Usher综合征（US）的特征是因色素性视网膜炎（RP）导致视力丧失和耳聋。US有三种临床亚型，但即使在每个亚型内，严重程度也有所不同。由[基因名称未给出]编码的肌球蛋白VIIA已被确定为US的致病基因之一。本研究旨在确定[基因名称未给出]相互作用以影响US症状表现的途径和其他基因。
在本研究中，我们使用BXD重组近交（RI）小鼠的视网膜组织来检测[基因名称未给出]的表达并进行基因定位。使用GeneNetwork进行表达定量性状位点（eQTL）、单核苷酸多态性（SNP）和基因相关性分析。使用WebGestalt进行基因集富集分析，并使用基因凝聚分析工具进行基因网络构建。
我们发现[基因名称未给出]受到[调控方式未给出]调控，在不同的BXD品系中表达水平各异。在此，我们提出一个由40个基因组成的遗传网络，其表达与[基因名称未给出]高度相关。在这些基因中，六个与视网膜疾病有关，三个与耳聋有关，五个与[基因名称未给出]共享一个转录因子。基因本体和途径分析揭示了离子通道活性[相关内容未明确]与US之间的紧密联系。
尽管[基因名称未给出]是I型US的致病基因，但该基因与许多其他基因和途径共同作用以影响US的严重程度。在[基因名称未给出]的遗传网络、途径和基因本体类别中发现的许多基因都与耳聋或失明有关。需要进一步研究以检查这些基因之间的具体关系，这可能有助于US的治疗。
