Session Information
Date: Saturday, October 6, 2018
Session Title: Genetics (Non-PD)
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: To unravel the disease mechanisms underlying neurodegeneration with brain iron accumulation (NBIA) and to identify potential novel disease genes.
Background: NBIA is clinically and genetically a heterogeneous group of movement disorders characterized by iron accumulation in the basal ganglia. The questions remains why and how iron accumulates so focally in the basal ganglia as only two of the 10 NBIA genes are directly involved in iron metabolism. It is also not known if the iron accumulation contributes to disease. Additionally, a large proportion of the NBIA cases remain genetically undiagnosed.
Methods: 75 HPO annotated genes involved in abnormality of the basal ganglia and 28 HPO annotated genes related to abnormality of iron metabolism were used to generate gene co-expression networks using GeneNetwork*. A PANTHER overrepresentation test for Gene Ontology (GO) slim biological process was performed using Fisher’s Exact with FDR multiple test correction.
Results: Constructing a gene co-expression network specific for abnormalities of the basal ganglia that included 2 NBIA genes, we identified DNA metabolic process and DNA repair as top hits. Metabolic processes were also significantly overrepresented including nitrogen compound and nucleobase-containing compound processes as well as primary metabolic processes. Of the 141 genes correlating with abnormality of the basal ganglia and 127 genes associated with abnormality of iron metabolism, 2 genes and 4 pseudogenes were shared between the two networks and highlight those as novel NBIA candidate genes.
Conclusions: Gene co-expression analysis exposed genes with a yet unrecognized role in abnormality in basal ganglia and in abnormality of iron homeostasis. DNA damage and DNA repair might play a role in diseases caused due to abnormalities of the basal ganglia including NBIAs.
To cite this abstract in AMA style:
M. van der Weijden, M. Tijssen, D. Verbeek. Studying genes involved in abnormalities of the basal ganglia and iron homeostasis using gene co-expression network analysis [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/studying-genes-involved-in-abnormalities-of-the-basal-ganglia-and-iron-homeostasis-using-gene-co-expression-network-analysis/. Accessed May 15, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/studying-genes-involved-in-abnormalities-of-the-basal-ganglia-and-iron-homeostasis-using-gene-co-expression-network-analysis/