Project description:Purpose: We applied polyA site sequencing (Passeq) to human Huntington's disease and control motor cortex and cerebellum to test if any genes change 3′UTR isoforms abundance. Methods: 3′ sequencing was performed on 6 motor cortices from grade 1 Huntington's patient brains, 4 motor cortices from grade 2 Huntington's patient brains, and 5 motor cortices from control brains. Cerebellum samples included 9 cerebella from grade 2-3 Huntington's patient brains, and 7 cerebella from control brains. To verify HTT isoforms in mice, sequencing was performed on 5 Q140 mouse striata and 3 wild-type mouse striata. Results: We report 11% of genes from Huntington's disease patient motor cortex exhibit a change in at least one of their 3′UTR isoforms, commensurate with the 11% of genes which show different total expression in HD motor cortex versus control. In contrast, gene isoform and expression changes are minimal (<5%) in Huntington's disease cerebellum versus controls. In the motor cortex, we show isoform and gene expression differs between between grade 1 and grade 2 brains. We identify a novel isoform of huntingtin mRNA which is conserved in wild-type and Huntington's model mice. Conclusions: This is the first study characterizing widespread alterations in 3′UTR isoform abundance in Huntington's disease. Alterations in isoform abundance may affect mRNA metabolism in Huntington's disease brains.
Project description:An Infinium microarray platform (HorvathMammalMethylChip40) was used to generate DNA methylation data from n=168 blood samples of a transgenic sheep model of Huntington's disease. 84 transgenic sheep and age matched control sheep.
Project description:Microarray methylation (Infinium® HumanMethylation450 BeadChip from Illumina) was performed on gingival tissue samples from 11 periodontitis cases and 12 age-matched healthy individuals.
Project description:Samples collected in the course of the TRACK HD study and used to analyse association between gene expression in blood and symptomatic progression of Huntington's disease Longitudinal analysis of UHDRS TMS versus gene expression in individual subjects followed by cross-sectional comparisons across phenotype groups at each timepoint
Project description:Affymetrix U133A expression levels for 12 symptomatic and 5 presymptomatic Huntington's disease patients versus 14 healthy controls. Keywords: other
Project description:Affymetrix U133A expression levels for 12 symptomatic and 5 presymptomatic Huntington's disease patients versus 14 healthy controls. Keywords: other
Project description:Codelink Human Uniset I, II, and 20K expression levels for 12 symptomatic and 5 presymptomatic Huntington's disease patients versus 14 healthy controls. Keywords: other
Project description:Hdac4 has been found to modulate symptoms in Huntington's Disease (HD) mouse models through an uknown mechanism unrelated to any enzymatic activity. We investigated the protein-protein interactions to gain insight into the role of Hdac4 in HD.