Allele-specific expression of Parkinson's disease susceptibility genes in human brain
| Autor: | Mathias Toft, Margrete Langmyhr, Sandra Pilar Henriksen, Chiara Cappelletti, Lasse Pihlstrøm, Wilma D.J. van de Berg |
|---|---|
| Přispěvatelé: | Anatomy and neurosciences, Amsterdam Neuroscience - Neurodegeneration |
| Rok vydání: | 2020 |
| Předmět: |
Potassium Channels
Science Parkinson's disease Gene Expression Single-nucleotide polymorphism Genome-wide association study Biology Quantitative trait Polymorphism Single Nucleotide Genome-wide association studies Article Gene expression Genetic variation Humans Genetic Predisposition to Disease Allele Gene Alleles Genetic association Genetics Multidisciplinary Quantitative traits Brain Nuclear Proteins Parkinson Disease Phosphoproteins Gene expression profiling ComputingMethodologies_PATTERNRECOGNITION rab GTP-Binding Proteins Medicine Glucosylceramidase Genome-Wide Association Study |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) Langmyhr, M, Henriksen, S P, Cappelletti, C, van de Berg, W D J, Pihlstrom, L & Toft, M 2021, ' Allele-specific expression of Parkinson’s disease susceptibility genes in human brain ', Scientific Reports, vol. 11, no. 1, 504 . https://doi.org/10.1038/s41598-020-79990-9, https://doi.org/10.1038/s41598-020-79990-9 Scientific Reports, 11(1):504. Nature Publishing Group |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-79990-9 |
| Popis: | Genome-wide association studies have identified genetic variation in genomic loci associated with susceptibility to Parkinson’s disease (PD), the most common neurodegenerative movement disorder worldwide. We used allelic expression profiling of genes located within PD-associated loci to identify cis-regulatory variation affecting gene expression. DNA and RNA were extracted from post-mortem superior frontal gyrus tissue and whole blood samples from PD patients and controls. The relative allelic expression of transcribed SNPs in 12 GWAS risk genes was analysed by real-time qPCR. Allele-specific expression was identified for 9 out of 12 genes tested (GBA, TMEM175, RAB7L1, NUCKS1, MCCC1, BCKDK, ZNF646, LZTS3, and WDHD1) in brain tissue samples. Three genes (GPNMB, STK39 and SIPA1L2) did not show significant allele-specific effects. Allele-specific effects were confirmed in whole blood for three genes (BCKDK, LZTS3 and MCCC1), whereas two genes (RAB7L1 and NUCKS1) showed brain-specific allelic expression. Our study supports the hypothesis that changes to the cis-regulation of gene expression is a major mechanism behind a large proportion of genetic associations in PD. Interestingly, allele-specific expression was also observed for coding variants believed to be causal variants (GBA and TMEM175), indicating that splicing and other regulatory mechanisms may be involved in disease development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|