The 4p16.3 Parkinson Disease Risk Locus Is Associated with GAK Expression and Genes Involved with the Synaptic Vesicle Membrane.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27508417.
- Also identified by DOI 10.1371/journal.pone.0160925 and PMC identifier 4980018.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Genome-wide association studies (GWAS) have identified the GAK/DGKQ/IDUA region on 4p16.3 among the top three risk loci for Parkinson's disease (PD), but the specific gene and risk mechanism are unclear. Here, we report transcripts containing the 3' clathrin-binding domain of GAK identified by RNA deep-sequencing in post-mortem human brain tissue as having increased expression in PD. Furthermore, carriers of 4p16.3 PD GWAS risk SNPs show decreased expression of one of these transcripts, GAK25 (Gencode Transcript 009), which correlates with the expression of genes functioning in the synaptic vesicle membrane. Together, these findings provide strong evidence for GAK clathrin-binding- and J-domain transcripts' influence on PD pathogenicity, and for a role for GAK in regulating synaptic function in PD.
Medical subject headings
- Chromosomes, Human, Pair 4
- Intracellular Signaling Peptides and Proteins
- Parkinson Disease
- Polymorphism, Single Nucleotide
- Protein Serine-Threonine Kinases
- Synaptic Vesicles