PDF(Pubmed)
Abstract：
The dog retina contains a central macula-like region, and there are reports of central retinal disorders in dogs with shared genetic etiologies with humans. Defining central/peripheral gene expression profiles may provide insight into the suitability of dogs as models for human disorders. We determined central/peripheral posterior eye gene expression profiles in dogs and interrogated inherited retinal and macular disease-associated genes for differential expression between central and peripheral regions. Bulk tissue RNA sequencing was performed on 8 mm samples of the dog central and superior peripheral regions, sampling retina and retinal pigmented epithelium/choroid separately. Reads were mapped to CanFam3.1, read counts were analyzed to determine significantly differentially expressed genes (DEGs). A similar analytic pipeline was used with a published bulk-tissue RNA sequencing human dataset. Pathways and processes involved in significantly DEGs were identified (Database for Annotation, Visualization and Integrated Discovery). Dogs and humans shared the extent and direction of central retinal differential gene expression, with multiple shared biological pathways implicated in differential expression. Many genes implicated in heritable retinal disorders in dogs and humans were differentially expressed between central and periphery. Approximately half of genes associated with human age-related macular degeneration were differentially expressed in human and dog tissues. We have identified similarities and differences in central/peripheral gene expression profiles between dogs and humans which can be applied to further define the relevance of dogs as models for human retinal disorders.
摘要：
狗的视网膜含有中央黄斑样区域,并且有报道称与人类有共同遗传病因的狗的中央视网膜疾病。定义中枢/外周基因表达谱可以提供对狗作为人类疾病模型的适用性的见解。我们确定了狗的中央/周围后眼基因表达谱，并询问了遗传性视网膜和黄斑疾病相关基因，以确定中央和周围区域之间的差异表达。对狗中央和上外周区域的8mm样本进行体组织RNA测序，分别取样视网膜和视网膜色素上皮/脉络膜。将读数映射到CanFam3.1,分析读数计数以确定显著差异表达的基因(DEG)。类似的分析管道与已发表的批量组织RNA测序人类数据集一起使用。确定了涉及显著DEG的路径和过程(注释数据库，可视化和集成发现)。狗和人类共享视网膜中央差异基因表达的程度和方向，与差异表达有关的多个共享生物途径。许多与狗和人类遗传性视网膜疾病有关的基因在中枢和外周之间差异表达。大约一半与人类年龄相关性黄斑变性相关的基因在人和狗组织中差异表达。我们已经确定了狗和人类之间的中枢/外周基因表达谱的相似性和差异,其可用于进一步定义狗作为人类视网膜疾病模型的相关性。
