The splice site variant rs11078928 may be associated with a genotype-dependent alteration in expression of GSDMB transcripts

BMC Genomics

Research Article

Andrew R Wood¹  Dorota Pasko¹  Anna Murray¹  Tim Frayling¹  Marcus Tuke¹  Lorna W Harries²  Jonathan M Locke²  Faer S Morrison² 

[1] Genetics of Complex Traits, University of Exeter Medical School, EX1 2LU, Exeter, UK;RNA mediated mechanisms of disease group, University of Exeter Medical School, EX2 5DW, Exeter, UK;

关键词: GSDMB;    Rs11078928;    Asthma;    Autoimmune disease;    GWAS;    SNP;    Alternative mRNA splicing;   

DOI  :  10.1186/1471-2164-14-627

 received in 2013-04-08, accepted in 2013-09-16,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundMany genetic variants have been associated with susceptibility to complex traits by genome wide association studies (GWAS), but for most, causal genes and mechanisms of action have yet to be elucidated. Using bioinformatics, we identified index and proxy variants associated with autoimmune disease susceptibility, with the potential to affect splicing of candidate genes. PCR and sequence analysis of whole blood RNA samples from population controls was then carried out for the 8 most promising variants to determine the effect of genetic variation on splicing of target genes.ResultsWe identified 31 splice site SNPs with the potential to affect splicing, and prioritised 8 to determine the effect of genotype on candidate gene splicing. We identified that variants rs11078928 and rs2014886 were associated with altered splicing of the GSDMB and TSFM genes respectively. rs11078928, present in the asthma and autoimmune disease susceptibility locus on chromosome 17q12-21, was associated with the production of a novel Δ exon5-8 transcript of the GSDMB gene, and a separate decrease in the percentage of transcripts with inclusion of exon 6, whereas the multiple sclerosis susceptibility variant rs2014886, was associated with an alternative TFSM transcript encompassing a short cryptic exon within intron 2.ConclusionsOur findings demonstrate the utility of a bioinformatic approach in identification and prioritisation of genetic variants effecting splicing of their host genes, and suggest that rs11078928 and rs2014886 may affect the splicing of the GSDMB and TSFM genes respectively.

【 授权许可】

Unknown   
© Morrison et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.