RT Journal Article
SR Electronic
T1 Next-generation profiling to identify the molecular etiology of Parkinson dementia
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams & Wilkins
SP e75
DO 10.1212/NXG.0000000000000075
VO 2
IS 3
A1 Henderson-Smith, Adrienne
A1 Corneveaux, Jason J.
A1 De Both, Matthew
A1 Cuyugan, Lori
A1 Liang, Winnie S.
A1 Huentelman, Matthew
A1 Adler, Charles
A1 Driver-Dunckley, Erika
A1 Beach, Thomas G.
A1 Dunckley, Travis L.
YR 2016
UL http://ng.neurology.org/content/2/3/e75.abstract
AB Objective: We sought to determine the underlying cortical gene expression changes associated with Parkinson dementia using a next-generation RNA sequencing approach.Methods: In this study, we used RNA sequencing to evaluate differential gene expression and alternative splicing in the posterior cingulate cortex from neurologically normal control patients, patients with Parkinson disease, and patients with Parkinson disease with dementia.Results: Genes overexpressed in both disease states were involved with an immune response, whereas shared underexpressed genes functioned in signal transduction or as components of the cytoskeleton. Alternative splicing analysis produced a pattern of immune and RNA-processing disturbances.Conclusions: Genes with the greatest degree of differential expression did not overlap with genes exhibiting significant alternative splicing activity. Such variation indicates the importance of broadening expression studies to include exon-level changes because there can be significant differential splicing activity with potential structural consequences, a subtlety that is not detected when examining differential gene expression alone, or is underrepresented with probe-limited array technology.ATXN2=ataxin-2; CAM=cell adhesion molecule; CON=controls; CRH=corticotropin-releasing hormone; CSF3=granulocyte colony-stimulating factor; DE=differential gene expression; DLB=dementia with Lewy bodies; dPSI=delta PSI; DSM-IV=Diagnostic and Statistical Manual of Mental Disorders, 4th edition; DST=dystonin; fc=fold change; GO=gene ontology; HSPH1=heat shock protein 105 kDa; KRT5=keratin 5; LRRFIP1=leucine-rich repeat flightless-interacting protein 1; NF-κB=nuclear factor κB; OPKM=observations per kilobase of transcript length per million aligned reads; PD=Parkinson disease; PD-D=Parkinson disease with dementia; PENK=proenkephalin; PSI=percent spliced in; qRT=quantitative real-time; RBCC=N-terminal RING finger/B-box/coiled coil; RELA=rel-like domain-containing; RNA-seq=RNA sequencing; RPKM=reads per kilobase of transcript length per million aligned reads; SELE=selectin-E; SRRM1=serine/arginine repetitive matrix 1; SST=somatostatin; TRIM=tripartite motif; TRIM9=tripartite motif 9; VGF=Vgf nerve growth factor