Kondrychyn Igor, Robra Lena, Thirumalai Vatsala
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka 560065, India.
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, Karnataka 560065, India
G3 (Bethesda). 2017 Aug 7;7(8):2577-2593. doi: 10.1534/g3.117.042622.
Several genes that have been implicated in autism spectrum disorders (ASDs) have multiple transcripts. Therefore, comprehensive transcript annotation is critical for determining the respective gene function. The autism susceptibility candidate 2 () gene is associated with various neurological disorders, including autism and brain malformation. AUTS2 is important for activation of transcription of neural specific genes, neuronal migration, and neurite outgrowth. Here, we present evidence for significant transcriptional complexity in the gene locus in the zebrafish genome, as well as in genomic loci of paralogous genes and Several genes that have been implicated in ASDs are large and have multiple transcripts. Neurons are especially enriched with longer transcripts compared to nonneural cell types. The human autism susceptibility candidate 2 () gene is ∼1.2 Mb long and is implicated in a number of neurological disorders including autism, intellectual disability, addiction, and developmental delay. Recent studies show AUTS2 to be important for activation of transcription of neural specific genes, neuronal migration, and neurite outgrowth. However, much remains to be understood regarding the transcriptional complexity and the functional roles of AUTS2 in neurodevelopment. Zebrafish provide an excellent model system for studying both these questions. We undertook genomic identification and characterization of and its paralogous genes in zebrafish. There are four family genes in zebrafish: , , , and The absence of complete annotation of their structures hampers functional studies. We present evidence for transcriptional complexity of these four genes mediated by alternative splicing and alternative promoter usage. Furthermore, the expression of the various paralogs is tightly regulated both spatially and developmentally. Our findings suggest that auts2 paralogs serve distinct functions in the development and functioning of target tissues.
一些与自闭症谱系障碍（ASD）相关的基因有多个转录本。因此，全面的转录本注释对于确定各自的基因功能至关重要。自闭症易感候选基因2（AUTS2）与多种神经疾病相关，包括自闭症和脑畸形。AUTS2对神经特异性基因转录的激活、神经元迁移和神经突生长很重要。在这里，我们提供证据表明斑马鱼基因组中AUTS2基因座以及同源基因AUTS2b和AUTS2c的基因组位点存在显著的转录复杂性。一些与ASD相关的基因很大且有多个转录本。与非神经细胞类型相比，神经元中较长的转录本尤其丰富。人类自闭症易感候选基因2（AUTS2）约1.2兆碱基长，与多种神经疾病有关，包括自闭症、智力残疾、成瘾和发育迟缓。最近的研究表明AUTS2对神经特异性基因转录的激活、神经元迁移和神经突生长很重要。然而，关于AUTS2在神经发育中的转录复杂性和功能作用仍有许多有待了解。斑马鱼为研究这两个问题提供了一个极好的模型系统。我们对斑马鱼中的AUTS2及其同源基因进行了基因组鉴定和表征。斑马鱼中有四个AUTS2家族基因：auts2a、auts2b、auts2c和auts2d。它们结构的完整注释缺失阻碍了功能研究。我们提供证据表明这四个基因通过可变剪接和可变启动子使用介导转录复杂性。此外，各种同源基因的表达在空间和发育上都受到严格调控。我们的研究结果表明，auts2同源基因在靶组织的发育和功能中发挥不同的作用。
