computational characterization of 3′ splice variants in the gfap isoform family计算特征的3u2032剪接变体gfap的同种型家庭.pdfVIP

Computational Characterization of 39 Splice Variants in the GFAP Isoform Family 1 2 2¤ 1. 2 . Sarah E. Boyd , Betina Nair , Sze Woei Ng , Jonathan M. Keith , Jacqueline M. Orian * 1 School of Mathematical Sciences, Monash University, Clayton, Victoria, Australia, 2 Department of Biochemistry, La Trobe University, Bundoora, Victoria, Australia 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 39 end splicing have been identified from modifications within intron 7, resulting in the generation of exon 7a (GFAPd/e) and 7b (GFAPk). 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 com