Previous studies have suggested that the level of transcriptional activity of any given gene can be correlated with gene sequence variations that are physically close to that gene. These variations might be in promoter or other non-coding elements that influence how rapidly mRNA is synthesized or its stability within a cell. Many such expression quantitative trait loci (eQTLs) have been mapped in different tissues and the aim of this project is to identify eQTLs in human brain with a view to understanding how genetic variability influences expression and underlies disease risk. We have measured mRNA expression in several different brain regions from a series of human brains that were genotyped by the Molecular Genetics Section of the Laboratory of Neurogenetics. Using a series of computational approaches, we were able to show that most eQTLs are found consistently across different brain regions suggesting that many common genetic variants affect gene expression across tissues. Part of this data was mined to try to identify how genetic variation associated with lifetime risk of Parkinsons disease influences gene expression as part of a genomewide association study (GWAS) reported this year. We have expanded the series of brain samples now to several hundred and are exploring the use of laser-capture microdissection to give a more refined view of gene expression by focusing on specific groups of neurons. We have also begun to apply next generation sequencing methods to provide a deeper view of gene expression in the brain including variation such as RNA splicing and editing.
| Erskine, Daniel; Ding, Jinhui; Thomas, Alan J et al. (2018) Molecular changes in the absence of severe pathology in the pulvinar in dementia with Lewy bodies. Mov Disord 33:982-991 |
| Chen-Plotkin, Alice S; Albin, Roger; Alcalay, Roy et al. (2018) Finding useful biomarkers for Parkinson's disease. Sci Transl Med 10: |
| Nuriel, Tal; Peng, Katherine Y; Ashok, Archana et al. (2017) The Endosomal-Lysosomal Pathway Is Dysregulated by APOE4 Expression in Vivo. Front Neurosci 11:702 |
| Dillman, Allissa A; Majounie, Elisa; Ding, Jinhui et al. (2017) Transcriptomic profiling of the human brain reveals that altered synaptic gene expression is associated with chronological aging. Sci Rep 7:16890 |
| Civiero, Laura; Cogo, Susanna; Kiekens, Anneleen et al. (2017) PAK6 Phosphorylates 14-3-3? to Regulate Steady State Phosphorylation of LRRK2. Front Mol Neurosci 10:417 |
| Yellajoshyula, Dhananjay; Liang, Chun-Chi; Pappas, Samuel S et al. (2017) The DYT6 Dystonia Protein THAP1 Regulates Myelination within the Oligodendrocyte Lineage. Dev Cell 42:52-67.e4 |
| Hibar, Derrek P (see original citation for additional authors) (2017) Novel genetic loci associated with hippocampal volume. Nat Commun 8:13624 |
| Cookson, Mark R (2017) RNA-binding proteins implicated in neurodegenerative diseases. Wiley Interdiscip Rev RNA 8: |
| Cookson, Mark R (2017) Gene Linkage and Systems Biology. Adv Neurobiol 15:479-489 |
| Soreq, Lilach; UK Brain Expression Consortium; North American Brain Expression Consortium et al. (2017) Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging. Cell Rep 18:557-570 |
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