Genomes and Genes
Lorna W Harries
Affiliation: University of Exeter
- Morrison F, Locke J, Wood A, Tuke M, Pasko D, Murray A, et al. The splice site variant rs11078928 may be associated with a genotype-dependent alteration in expression of GSDMB transcripts. BMC Genomics. 2013;14:627 pubmed publisher....
- Latorre E, Harries L. Splicing regulatory factors, ageing and age-related disease. Ageing Res Rev. 2017;36:165-170 pubmed publisher..These important splicing regulators have been implicated in age-related disease, and in the ageing process itself. This review will outline the important contribution of splicing regulator proteins to ageing and age-related disease. ..
- Locke J, Hysenaj G, Wood A, Weedon M, Harries L. Targeted allelic expression profiling in human islets identifies cis-regulatory effects for multiple variants identified by type 2 diabetes genome-wide association studies. Diabetes. 2015;64:1484-91 pubmed publisher..The results of this study support the hypothesis that changes to cis-regulation of gene expression are involved in a large proportion of SNP associations with type 2 diabetes susceptibility. ..
- Latorre E, Pilling L, Lee B, Bandinelli S, Melzer D, Ferrucci L, et al. The VEGFA156b isoform is dysregulated in senescent endothelial cells and may be associated with prevalent and incident coronary heart disease. Clin Sci (Lond). 2018;132:313-325 pubmed publisher..Dysregulated splicing factor expression is a key feature of senescent cardiomyocytes and endothelial cells. Altered splicing of key cardiac or endothelial genes may contribute to the risk of CHD in the human population. ..
- Harries L, Ellard S, Stride A, Morgan N, Hattersley A. Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Hum Mol Genet. 2006;15:2216-24 pubmed..We conclude that all three isomers may be critical for beta-cell function and could play a role in both the developing and mature beta cell. ..
- Harries L, Locke J, Shields B, Hanley N, Hanley K, Steele A, et al. The diabetic phenotype in HNF4A mutation carriers is moderated by the expression of HNF4A isoforms from the P1 promoter during fetal development. Diabetes. 2008;57:1745-52 pubmed publisher....
- Harries L, Sloman M, Sellers E, Hattersley A, Ellard S. Diabetes susceptibility in the Canadian Oji-Cree population is moderated by abnormal mRNA processing of HNF1A G319S transcripts. Diabetes. 2008;57:1978-82 pubmed publisher..A combination of abnormal splicing and reduced activity of the G319S protein may explain the diabetes susceptibility. ..
- Harries L, McCulloch L, Holley J, Rawling T, Welters H, Kos K. A role for SPARC in the moderation of human insulin secretion. PLoS ONE. 2013;8:e68253 pubmed publisher....
- Harries L, Perry J, McCullagh P, Crundwell M. Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer. BMC Cancer. 2010;10:315 pubmed publisher..The alterations in isoform usage we detect highlights the potential importance of alternative mRNA processing and moderation of mRNA stability as potentially important disease mechanisms. ..
- Latorre E, Birar V, Sheerin A, Jeynes J, Hooper A, Dawe H, et al. Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence. BMC Cell Biol. 2017;18:31 pubmed publisher..Small molecule modulators of such targets may therefore represent promising novel anti-degenerative therapies. ..
- Haque S, Harries L. Circular RNAs (circRNAs) in Health and Disease. Genes (Basel). 2017;8: pubmed publisher..In this review, we explore the state of knowledge on this exciting class of transcripts in regulating gene expression and discuss their emerging role in health and disease. ..
- Harries L, Brown J, Gloyn A. Species-specific differences in the expression of the HNF1A, HNF1B and HNF4A genes. PLoS ONE. 2009;4:e7855 pubmed publisher..We conclude that alterations to expression of HNF isoforms may underlie some of the phenotypic variation caused by mutations in these genes. ..
- Jeffery N, Richardson S, Beall C, Harries L. The species origin of the cellular microenvironment influences markers of beta cell fate and function in EndoC-?H1 cells. Exp Cell Res. 2017;361:284-291 pubmed publisher....