Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

A spotter’s guide to SNPtic exons: The common splice variants underlying some SNP–phenotype correlations

Keegan, N.P. and Fletcher, S. (2021) A spotter’s guide to SNPtic exons: The common splice variants underlying some SNP–phenotype correlations. Molecular Genetics & Genomic Medicine . Early View.

[img]
Preview
PDF - Published Version
Download (1MB) | Preview
Free to read: https://doi.org/10.1002/mgg3.1840
*No subscription required

Abstract

Background

Cryptic exons are typically characterised as deleterious splicing aberrations caused by deep intronic mutations. However, low-level splicing of cryptic exons is sometimes observed in the absence of any pathogenic mutation. Five recent reports have described how low-level splicing of cryptic exons can be modulated by common single-nucleotide polymorphisms (SNPs), resulting in phenotypic differences amongst different genotypes.

Methods

We sought to investigate whether additional ‘SNPtic’ exons may exist, and whether these could provide an explanatory mechanism for some of the genotype–phenotype correlations revealed by genome-wide association studies.

We thoroughly searched the literature for reported cryptic exons, cross-referenced their genomic coordinates against the dbSNP database of common SNPs, then screened out SNPs with no reported phenotype associations.

Results

This method discovered five probable SNPtic exons in the genes APC, FGB, GHRL, MYPBC3 and OTC. For four of these five exons, we observed that the phenotype associated with the SNP was compatible with the predicted splicing effect of the nucleotide change, whilst the fifth (in GHRL) likely had a more complex splice-switching effect.

Conclusion

Application of our search methods could augment the knowledge value of future cryptic exon reports and aid in generating better hypotheses for genome-wide association studies.

Item Type: Journal Article
Murdoch Affiliation(s): Centre for Molecular Medicine and Innovative Therapeutics (CMMIT)
Publisher: Wiley
Copyright: © 2021 The Authors.
URI: http://researchrepository.murdoch.edu.au/id/eprint/62816
Item Control Page Item Control Page

Downloads

Downloads per month over past year