A mutation in a splicing factor that causes retinitis pigmentosa has a transcriptome-wide effect on mRNA splicing
| dc.contributor.author | Korir, Paul K | |
| dc.contributor.author | Roberts, Lisa | |
| dc.contributor.author | Ramesar, Raj | |
| dc.contributor.author | Seoighe, Cathal | |
| dc.date.accessioned | 2015-02-05T13:45:55Z | |
| dc.date.available | 2015-02-05T13:45:55Z | |
| dc.date.issued | 2014-06-27 | |
| dc.date.updated | 2015-01-15T17:57:52Z | |
| dc.description.abstract | Background: Substantial progress has been made in the identification of sequence elements that control mRNA splicing and the genetic variants in these elements that alter mRNA splicing (referred to as splicing quantitative trait loci – sQTLs). Genetic variants that affect mRNA splicing in trans are harder to identify because their effects can be more subtle and diffuse, and the variants are not co-located with their targets. We carried out a transcriptome-wide analysis of the effects of a mutation in a ubiquitous splicing factor that causes retinitis pigmentosa (RP) on mRNA splicing, using exon microarrays. Results: Exon microarray data was generated from whole blood samples obtained from four individuals with a mutation in the splicing factor PRPF8 and four sibling controls. Although the mutation has no known phenotype in blood, there was evidence of widespread differences in splicing between cases and controls (affecting approximately 20% of exons). Most probesets with significantly different inclusion (defined as the expression intensity of the exon divided by the expression of the corresponding transcript) between cases and controls had higher inclusion in cases and corresponded to exons that were shorter than average, AT rich, located towards the 5’ end of the gene and flanked by long introns. Introns flanking affected probesets were particularly depleted for the shortest category of introns, associated with splicing via intron definition. Conclusions: Our results show that a mutation in a splicing factor, with a phenotype that is restricted to retinal tissue, acts as a trans-sQTL cluster in whole blood samples. Characteristics of the affected exons suggest that they are spliced co-transcriptionally and via exon definition. However, due to the small sample size available for this study, further studies are required to confirm the widespread impact of this PRPF8 mutation on mRNA splicing outside the retina. | en_ZA |
| dc.identifier.apacitation | Korir, P. K., Roberts, L., Ramesar, R., & Seoighe, C. (2014). A mutation in a splicing factor that causes retinitis pigmentosa has a transcriptome-wide effect on mRNA splicing. <i>BMC Research Notes</i>, http://hdl.handle.net/11427/12381 | en_ZA |
| dc.identifier.chicagocitation | Korir, Paul K, Lisa Roberts, Raj Ramesar, and Cathal Seoighe "A mutation in a splicing factor that causes retinitis pigmentosa has a transcriptome-wide effect on mRNA splicing." <i>BMC Research Notes</i> (2014) http://hdl.handle.net/11427/12381 | en_ZA |
| dc.identifier.citation | Korir, P. K., Roberts, L., Ramesar, R., & Seoighe, C. (2014). A mutation in a splicing factor that causes retinitis pigmen-tosa has a transcriptome-wide effect on mRNA splicing. BMC research notes, 7(1), 401. | en_ZA |
| dc.identifier.issn | 1756-0500 | |
| dc.identifier.ris | TY - Journal Article AU - Korir, Paul K AU - Roberts, Lisa AU - Ramesar, Raj AU - Seoighe, Cathal AB - Background: Substantial progress has been made in the identification of sequence elements that control mRNA splicing and the genetic variants in these elements that alter mRNA splicing (referred to as splicing quantitative trait loci – sQTLs). Genetic variants that affect mRNA splicing in trans are harder to identify because their effects can be more subtle and diffuse, and the variants are not co-located with their targets. We carried out a transcriptome-wide analysis of the effects of a mutation in a ubiquitous splicing factor that causes retinitis pigmentosa (RP) on mRNA splicing, using exon microarrays. Results: Exon microarray data was generated from whole blood samples obtained from four individuals with a mutation in the splicing factor PRPF8 and four sibling controls. Although the mutation has no known phenotype in blood, there was evidence of widespread differences in splicing between cases and controls (affecting approximately 20% of exons). Most probesets with significantly different inclusion (defined as the expression intensity of the exon divided by the expression of the corresponding transcript) between cases and controls had higher inclusion in cases and corresponded to exons that were shorter than average, AT rich, located towards the 5’ end of the gene and flanked by long introns. Introns flanking affected probesets were particularly depleted for the shortest category of introns, associated with splicing via intron definition. Conclusions: Our results show that a mutation in a splicing factor, with a phenotype that is restricted to retinal tissue, acts as a trans-sQTL cluster in whole blood samples. Characteristics of the affected exons suggest that they are spliced co-transcriptionally and via exon definition. However, due to the small sample size available for this study, further studies are required to confirm the widespread impact of this PRPF8 mutation on mRNA splicing outside the retina. DA - 2014-06-27 DB - OpenUCT DO - 10.1186/1756-0500-7-401 DP - University of Cape Town J1 - BMC Research Notes LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 SM - 1756-0500 T1 - A mutation in a splicing factor that causes retinitis pigmentosa has a transcriptome-wide effect on mRNA splicing TI - A mutation in a splicing factor that causes retinitis pigmentosa has a transcriptome-wide effect on mRNA splicing UR - http://hdl.handle.net/11427/12381 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/12381 | |
| dc.identifier.uri | http://dx.doi.org/10.1186/1756-0500-7-401 | |
| dc.identifier.vancouvercitation | Korir PK, Roberts L, Ramesar R, Seoighe C. A mutation in a splicing factor that causes retinitis pigmentosa has a transcriptome-wide effect on mRNA splicing. BMC Research Notes. 2014; http://hdl.handle.net/11427/12381. | en_ZA |
| dc.language.rfc3066 | en | |
| dc.publisher | BioMed Central | en_ZA |
| dc.publisher.department | MRC/UCT Human Genetics Research Unit | en_ZA |
| dc.publisher.faculty | Faculty of Health Sciences | en_ZA |
| dc.publisher.institution | University of Cape Town | |
| dc.rights | Creative Commons Attribution 4.0 International (CC BY 4.0) | * |
| dc.rights.holder | Korir et al.; licensee BioMed Central Ltd. | |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_ZA |
| dc.source | BMC Research Notes | en_ZA |
| dc.source.uri | http://www.biomedcentral.com/1756-0500/ | |
| dc.subject.other | mRNA splicing | en_ZA |
| dc.subject.other | Retinitis pigmentosa | en_ZA |
| dc.subject.other | Exon array | en_ZA |
| dc.subject.other | PRPF8 | en_ZA |
| dc.title | A mutation in a splicing factor that causes retinitis pigmentosa has a transcriptome-wide effect on mRNA splicing | en_ZA |
| dc.type | Journal Article | en_ZA |
| uct.type.filetype | Text | |
| uct.type.filetype | Image | |
| uct.type.publication | Research | en_ZA |
| uct.type.resource | Article | en_ZA |