Gene co-expression network analysis of dysferlinopathy: Altered cellular processes and functional prediction of TOR1AIP1 a novel muscular dystrophy gene

Cali-Daylan A. E., Dincer P.

NEUROMUSCULAR DISORDERS, vol.27, no.3, pp.269-277, 2017 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 3
  • Publication Date: 2017
  • Doi Number: 10.1016/j.nmd.2016.10.011
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.269-277
  • Hacettepe University Affiliated: Yes


Dysferlinopathy, caused by a dysferlin gene mutation, is a clinically heterogeneous autosomal recessive muscle disease characterized by progressive muscle degeneration. The dysferlin protein's functions and dysferlinopathy disease pathogenesis are not fully explored, and there is no specific treatment available that can alter the disease progression. This study uses publicly available dysferlinopathy patient microarray data to construct a gene co-expression network and investigates significant cellular pathways and their key players in dysferlinopathy pathogenesis. Extracellular matrix deposition, inflammation, mitochondrial abnormalities and protein degradation were found to be important in dysferlinopathy. Out of the hub genes, OXRI and TIMP1 were selected through literature search as candidate genes for possible biomarker and molecular therapeutic target studies. A recently identified muscular dystrophy gene TORL4IPI was detected as a hub gene in dysferlinopathy. Co-expression and protein sequence feature analysis Were adopted to predict TORIAIPI's function. Our results suggest that LAP1 protein encoded by TORIAIPI may play a role in protein degradation possibly through transcriptional regulation in muscle tissue. These findings extend dysferlinopathy pathogenesis by presenting key genes and also suggest a novel function for a poorly characterized gene. (C) 2016 Elsevier B.V. All rights reserved.