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Exp Physiol DOI:10.1113/EP085129

Tracks through the genome to physiological events.

Publication TypeJournal Article
Year of Publication2015
AuthorsLipscombe, D, Pan, JQ, Schorge, S
JournalExp Physiol
Volume100
Issue12
Pages1429-40
Date Published2015 Dec
ISSN1469-445X
KeywordsAnimals, Brain, Databases, Genetic, Exons, Genome, Humans, Proteins, RNA, Messenger
Abstract

NEW FINDINGS: What is the topic of this review? We discuss tools available to access genome-wide data sets that harbour cell-specific, brain region-specific and tissue-specific information on exon usage for several species, including humans. In this Review, we demonstrate how to access this information in genome databases and its enormous value to physiology. What advances does it highlight? The sheer scale of protein diversity that is possible from complex genes, including those that encode voltage-gated ion channels, is vast. But this choice is critical for a complete understanding of protein function in the most physiologically relevant context. Many proteins of great interest to physiologists and neuroscientists are structurally complex and located in specialized subcellular domains, such as neuronal synapses and transverse tubules of muscle. Genes that encode these critical signalling molecules (receptors, ion channels, transporters, enzymes, cell adhesion molecules, cell-cell interaction proteins and cytoskeletal proteins) are similarly complex. Typically, these genes are large; human Dystrophin (DMD) encodes a cytoskeletal protein of muscle and it is the largest naturally occurring gene at a staggering 2.3 Mb. Large genes contain many non-coding introns and coding exons; human Titin (TTN), which encodes a protein essential for the assembly and functioning of vertebrate striated muscles, has over 350 exons and consequently has an enormous capacity to generate different forms of Titin mRNAs that have unique exon combinations. Functional and pharmacological differences among protein isoforms originating from the same gene may be subtle but nonetheless of critical physiological significance. Standard functional, immunological and pharmacological approaches, so useful for characterizing proteins encoded by different genes, typically fail to discriminate among splice isoforms of individual genes. Tools are now available to access genome-wide data sets that harbour cell-specific, brain region-specific and tissue-specific information on exon usage for several species, including humans. In this Review, we demonstrate how to access this information in genome databases and its enormous value to physiology.

URLhttp://dx.doi.org/10.1113/EP085129
DOI10.1113/EP085129
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/26053180?dopt=Abstract

Alternate JournalExp. Physiol.
PubMed ID26053180
PubMed Central IDPMC5008151
Grant ListMH099448 / MH / NIMH NIH HHS / United States
MR/K000608/1 / / Medical Research Council / United Kingdom
104033 / / Wellcome Trust / United Kingdom
NS055251 / NS / NINDS NIH HHS / United States
R01 NS055251 / NS / NINDS NIH HHS / United States