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• W2076954429 endingPage "e33565" @default.
• W2076954429 startingPage "e33565" @default.
• W2076954429 abstract "Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) protein specific to central nervous system (CNS) astrocytes. It has been the subject of intense interest due to its association with neurodegenerative diseases, and because of growing evidence that IF proteins not only modulate cellular structure, but also cellular function. Moreover, GFAP has a family of splicing isoforms apparently more complex than that of other CNS IF proteins, consistent with it possessing a range of functional and structural roles. The gene consists of 9 exons, and to date all isoforms associated with 3′ end splicing have been identified from modifications within intron 7, resulting in the generation of exon 7a (GFAPδ/ε) and 7b (GFAPκ). To better understand the nature and functional significance of variation in this region, we used a Bayesian multiple change-point approach to identify conserved regions. This is the first successful application of this method to a single gene – it has previously only been used in whole-genome analyses. We identified several highly or moderately conserved regions throughout the intron 7/7a/7b regions, including untranslated regions and regulatory features, consistent with the biology of GFAP. Several putative unconfirmed features were also identified, including a possible new isoform. We then integrated multiple computational analyses on both the DNA and protein sequences from the mouse, rat and human, showing that the major isoform, GFAPα, has highly conserved structure and features across the three species, whereas the minor isoforms GFAPδ/ε and GFAPκ have low conservation of structure and features at the distal 3′ end, both relative to each other and relative to GFAPα. The overall picture suggests distinct and tightly regulated functions for the 3′ end isoforms, consistent with complex astrocyte biology. The results illustrate a computational approach for characterising splicing isoform families, using both DNA and protein sequences." @default.
• W2076954429 created "2016-06-24" @default.
• W2076954429 creator A5033879825 @default.
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• W2076954429 creator A5060901997 @default.
• W2076954429 creator A5071289978 @default.
• W2076954429 creator A5083075316 @default.
• W2076954429 date "2012-03-30" @default.
• W2076954429 modified "2023-09-26" @default.
• W2076954429 title "Computational Characterization of 3′ Splice Variants in the GFAP Isoform Family" @default.
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• W2076954429 doi "https://doi.org/10.1371/journal.pone.0033565" @default.
• W2076954429 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3316583" @default.
• W2076954429 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22479412" @default.
• W2076954429 hasPublicationYear "2012" @default.
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