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Transcriptional Complexity and Distinct Expression Patterns of auts2 Paralogs in Danio rerio

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 (AUTS2) gene is associated with various neurological d...

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Autores principales: Kondrychyn, Igor, Robra, Lena, Thirumalai, Vatsala
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555464/
https://www.ncbi.nlm.nih.gov/pubmed/28626003
http://dx.doi.org/10.1534/g3.117.042622
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author Kondrychyn, Igor
Robra, Lena
Thirumalai, Vatsala
author_facet Kondrychyn, Igor
Robra, Lena
Thirumalai, Vatsala
author_sort Kondrychyn, Igor
collection PubMed
description 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 (AUTS2) 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 auts2 gene locus in the zebrafish genome, as well as in genomic loci of auts2 paralogous genes fbrsl1 and fbrs. 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 (AUTS2) 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 auts2 and its paralogous genes in zebrafish. There are four auts2 family genes in zebrafish: auts2a, auts2b, fbrsl1, and fbrs. 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.
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spelling pubmed-55554642017-08-17 Transcriptional Complexity and Distinct Expression Patterns of auts2 Paralogs in Danio rerio Kondrychyn, Igor Robra, Lena Thirumalai, Vatsala G3 (Bethesda) Investigations 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 (AUTS2) 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 auts2 gene locus in the zebrafish genome, as well as in genomic loci of auts2 paralogous genes fbrsl1 and fbrs. 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 (AUTS2) 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 auts2 and its paralogous genes in zebrafish. There are four auts2 family genes in zebrafish: auts2a, auts2b, fbrsl1, and fbrs. 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. Genetics Society of America 2017-06-16 /pmc/articles/PMC5555464/ /pubmed/28626003 http://dx.doi.org/10.1534/g3.117.042622 Text en Copyright © 2017 Kondrychyn et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigations
Kondrychyn, Igor
Robra, Lena
Thirumalai, Vatsala
Transcriptional Complexity and Distinct Expression Patterns of auts2 Paralogs in Danio rerio
title Transcriptional Complexity and Distinct Expression Patterns of auts2 Paralogs in Danio rerio
title_full Transcriptional Complexity and Distinct Expression Patterns of auts2 Paralogs in Danio rerio
title_fullStr Transcriptional Complexity and Distinct Expression Patterns of auts2 Paralogs in Danio rerio
title_full_unstemmed Transcriptional Complexity and Distinct Expression Patterns of auts2 Paralogs in Danio rerio
title_short Transcriptional Complexity and Distinct Expression Patterns of auts2 Paralogs in Danio rerio
title_sort transcriptional complexity and distinct expression patterns of auts2 paralogs in danio rerio
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555464/
https://www.ncbi.nlm.nih.gov/pubmed/28626003
http://dx.doi.org/10.1534/g3.117.042622
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