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A new view of transcriptome complexity and regulation through the lens of local splicing variations
Alternative splicing (AS) can critically affect gene function and disease, yet mapping splicing variations remains a challenge. Here, we propose a new approach to define and quantify mRNA splicing in units of local splicing variations (LSVs). LSVs capture previously defined types of alternative spli...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801060/ https://www.ncbi.nlm.nih.gov/pubmed/26829591 http://dx.doi.org/10.7554/eLife.11752 |
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author | Vaquero-Garcia, Jorge Barrera, Alejandro Gazzara, Matthew R González-Vallinas, Juan Lahens, Nicholas F Hogenesch, John B Lynch, Kristen W Barash, Yoseph |
author_facet | Vaquero-Garcia, Jorge Barrera, Alejandro Gazzara, Matthew R González-Vallinas, Juan Lahens, Nicholas F Hogenesch, John B Lynch, Kristen W Barash, Yoseph |
author_sort | Vaquero-Garcia, Jorge |
collection | PubMed |
description | Alternative splicing (AS) can critically affect gene function and disease, yet mapping splicing variations remains a challenge. Here, we propose a new approach to define and quantify mRNA splicing in units of local splicing variations (LSVs). LSVs capture previously defined types of alternative splicing as well as more complex transcript variations. Building the first genome wide map of LSVs from twelve mouse tissues, we find complex LSVs constitute over 30% of tissue dependent transcript variations and affect specific protein families. We show the prevalence of complex LSVs is conserved in humans and identify hundreds of LSVs that are specific to brain subregions or altered in Alzheimer's patients. Amongst those are novel isoforms in the Camk2 family and a novel poison exon in Ptbp1, a key splice factor in neurogenesis. We anticipate the approach presented here will advance the ability to relate tissue-specific splice variation to genetic variation, phenotype, and disease. DOI: http://dx.doi.org/10.7554/eLife.11752.001 |
format | Online Article Text |
id | pubmed-4801060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-48010602016-03-22 A new view of transcriptome complexity and regulation through the lens of local splicing variations Vaquero-Garcia, Jorge Barrera, Alejandro Gazzara, Matthew R González-Vallinas, Juan Lahens, Nicholas F Hogenesch, John B Lynch, Kristen W Barash, Yoseph eLife Computational and Systems Biology Alternative splicing (AS) can critically affect gene function and disease, yet mapping splicing variations remains a challenge. Here, we propose a new approach to define and quantify mRNA splicing in units of local splicing variations (LSVs). LSVs capture previously defined types of alternative splicing as well as more complex transcript variations. Building the first genome wide map of LSVs from twelve mouse tissues, we find complex LSVs constitute over 30% of tissue dependent transcript variations and affect specific protein families. We show the prevalence of complex LSVs is conserved in humans and identify hundreds of LSVs that are specific to brain subregions or altered in Alzheimer's patients. Amongst those are novel isoforms in the Camk2 family and a novel poison exon in Ptbp1, a key splice factor in neurogenesis. We anticipate the approach presented here will advance the ability to relate tissue-specific splice variation to genetic variation, phenotype, and disease. DOI: http://dx.doi.org/10.7554/eLife.11752.001 eLife Sciences Publications, Ltd 2016-02-01 /pmc/articles/PMC4801060/ /pubmed/26829591 http://dx.doi.org/10.7554/eLife.11752 Text en © 2016, Vaquero-Garcia et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Computational and Systems Biology Vaquero-Garcia, Jorge Barrera, Alejandro Gazzara, Matthew R González-Vallinas, Juan Lahens, Nicholas F Hogenesch, John B Lynch, Kristen W Barash, Yoseph A new view of transcriptome complexity and regulation through the lens of local splicing variations |
title | A new view of transcriptome complexity and regulation through the lens of
local splicing variations |
title_full | A new view of transcriptome complexity and regulation through the lens of
local splicing variations |
title_fullStr | A new view of transcriptome complexity and regulation through the lens of
local splicing variations |
title_full_unstemmed | A new view of transcriptome complexity and regulation through the lens of
local splicing variations |
title_short | A new view of transcriptome complexity and regulation through the lens of
local splicing variations |
title_sort | new view of transcriptome complexity and regulation through the lens of
local splicing variations |
topic | Computational and Systems Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801060/ https://www.ncbi.nlm.nih.gov/pubmed/26829591 http://dx.doi.org/10.7554/eLife.11752 |
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