We have explored the associations between DNA variants in the genome, particularly single nucleotide polymorphisms (SNPs) and expression of nearby mRNA. At a genome wide level, there are many such associations found as expression quantitative trait loci (eQTLs). We have generated, and made publically available, one of the largest eQTL mapping sets in the human brain, with nearly 400 individuals with age range covering most of the human lifespan where genotype and expression data form microarrays is available. Primarily this is focused on two brain regions, the cerebellum and the frontal cerebral cortex, with ancillary datasets in other brain regions and on isolated cell types.
Our aim i s to provide a comprehensive view of the genomic control of gene expression in this complex organ that can be examined in a number of ways. We have examined the role of genetic variation in gene expression in a number of analyses over the past reporting period. For example, we have shown that while there is overlap in eQTLs between blood and brain there are also distinct differences that are not easily explained by gene expression levels. Ongoing analyses include an investigation into the relationship of age and expression in human brain. We are also moving these analyses forward to use novel techniques for measuring mRNA expression, including RNA-sequencing. As in prior reporting, we have seen these datasets used by other groups, particularly those interesting in genetic variation associated with neurological and psychiatric conditions. Several publications have resulted from the use of this publicly available resource.
| 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 |
Showing the most recent 10 out of 37 publications
