Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

PWC dataset for genome-wide association study of modifiers of risk of canine degenerative myelopathy in dogs homozygous for SOD1 mutation

ABSTRACT: Degenerative myelopathy (DM) is a canine disease very similar to amyotrophic lateral sclerosis (ALS) in humans. We previously showed that DM is a promising model for ALS, as genome-wide association identified a mutation in SOD1, a known ALS gene. In this study, we identify a modifier gene, SP110, which strongly affects overall disease risk and age-of-onset in Pembroke Welsh corgis at risk of DM. Dissecting the complex genetics of this disease in a model organism may lead to new insights about risk and progression in both canine and human patients. 15 DM-affected and 31 unaffected PWC homozygous for SOD1 mutation genotyped using the Illumina CanineHD array (~170,000 SNPs genomewide)

ORGANISM(S): Canis lupus familiaris

SUBMITTER: Kerstin Lindblad-Toh

PROVIDER: E-GEOD-80735 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:We established iPSCs from healthy donors, SOD1-ALS and TDP43-ALS patients. Using our differentiation protocol originally developed by Reinhardt et al.,2013, we diferentiated these iPSCs toward spinal motor neurons (MNs) and reproduce ALS pathology in a dish. To extend our understanding of finding different molecular mechanisms and pathways related to SOD1- and TDP43 mutations in ALS disease, we have performed a comprehensive gene expression profiling study using RNA-Seq of the iPSC-derived MN models from control individuals and carefully compared with those from SOD1-ALS and TDP43-ALS patients. To generate novel hypotheses of putative underlying molecular mechanisms in ALS, we used human induced pluripotent stem cell (hiPSCs)-derived motor neurons (MNs) from SOD1- and TARDBP (TDP-43 protein)-mutant-ALS patients and healthy controls to perform high-throughput RNA-sequencing (RNA-Seq). An integrated bioinformatics approach was employed to identify differentially expressed genes (DEGs) and key pathways underlying these familial forms of the disease (fALS). In TDP43-ALS, we found dysregulation of transcripts encoding components of the transcriptional machinery and transcripts involved in splicing regulation were particularly affected. In contrast, less is known about the role of SOD1 in RNA metabolism in motor neurons. Here we found that many transcripts relevant for mitochondrial function were specifically altered in SOD1-ALS, indicating transcriptional signatures and expression patterns can vary significantly depending on the causal gene that is mutated. Surprisingly, however, we identified a clear downregulation of genes involved in protein translation in SOD1-ALS suggesting that ALS-causing SOD1 mutations shift cellular RNA abundance profiles to cause neural dysfunction. Altogether, we provided here an extensive profiling of mRNA expression in two ALS models at the cellular level, corroborating the major role of RNA metabolism and protein translation as a common pathomechanism in ALS

Dataset Information

PWC dataset for genome-wide association study of modifiers of risk of canine degenerative myelopathy in dogs homozygous for SOD1 mutation

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure