Identification of gene fusions associated with amyotrophic lateral sclerosis.
Muscle Nerve
; 69(4): 477-489, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38305586
ABSTRACT
INTRODUCTION/AIMS:
Genetics is an important risk factor for amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. Recent findings demonstrate that in addition to specific genetic mutations, structural variants caused by genetic instability can also play a causative role in ALS. Genomic instability can lead to deletions, duplications, insertions, inversions, and translocations in the genome, and these changes can sometimes lead to fusion of distinct genes into a single transcript. Gene fusion events have been studied extensively in cancer; however, they have not been thoroughly investigated in ALS. The aim of this study was to determine whether gene fusions are present in ALS.METHODS:
Gene fusions were identified using STAR Fusion v1.10.0 software in bulk RNA-Seq data from human postmortem samples from publicly available data sets from Target ALS and the New York Genome Center ALS Consortium.RESULTS:
We report the presence of gene fusion events in several brain regions as well as in spinal cord samples in ALS. Although most gene fusions were intra-chromosomal events between neighboring genes and present in both ALS and control samples, there was a significantly greater number of unique gene fusions in ALS compared to controls. Lastly, we identified specific gene fusions with a significant burden in ALS, that were absent from both control samples and known cancer gene fusion databases.DISCUSSION:
Collectively, our findings reveal an enrichment of gene fusions in ALS and suggest that these events may be an additional genetic cause linked to ALS pathogenesis.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Neurodegenerativas
/
Esclerosis Amiotrófica Lateral
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article