Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls.
Project description:RATIONALE: Identification of genes that may be associated with developing certain types of cancer may someday provide important information about a person’s risk of getting cancer.
PURPOSE: This clinical trial is studying to see if certain genes may be associated with cancer in patients with cancer of the breast, prostate, lung, or colon and siblings of these patients.
Project description:Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS cases (8,224 AS, 1,437 APA), including changes in ALS-associated genes (e.g. ATXN2 and FUS), and cases of sporadic ALS (sALS; 2,229 AS, 716 APA). Furthermore, hnRNPH and other RNA-binding proteins are predicted as potential regulators of cassette exon AS events for both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS. Examination transcriptiome profiles in c9orf72-associated ALS, sporadic ALS and healthy control
Project description:Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease mainly affecting upper and lower motoneurons (MNs). In the last decades, several genes have been associated to the familial form of this disorder (fALS), thus depicting an extremely complex pathogenic landscape. The aim of this study was to identify convergent molecular underpinnings shared by ALS cases characterized by mutations in different genes using human induced pluripotent stem cells (hiPSCs).