Identification of gene fusions associated with amyotrophic lateral sclerosis

Yogindra Raghav, Allison A. Dilliott, Tiziana Petrozziello, Spencer E. Kim, James D. Berry, Merit E. Cudkowicz, Khashayar Vakili, Ernest Fraenkel, Sali M.K. Farhan, Ghazaleh Sadri-Vakili

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)477-489
Number of pages13
JournalMuscle and Nerve
Issue number4
StateAccepted/In press - 2024
Externally publishedYes


  • RNA-Seq
  • amyotrophic lateral sclerosis
  • gene fusion
  • genetics
  • neurodegenerative diseases


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