Találati lista | Tudóstér

001-es BibID:	BIBFORM016359
Első szerző:	Buonocore, Frederica
Cím:	Effects of cis-regulatory variation differ across regions of the adult human brain / Frederica Buonocore, Matthew J. Hill, Colin D. Campbell, Paul B. Oladimeji, Aaron R. Jeffries, Claire Troakes, Tibor Hortobagyi, Brenda P. Williams, Jonathan D. Cooper, Nicholas J. Bray
Dátum:	2010
ISSN:	0964-6906
Megjegyzések:	Cis-regulatory variation is considered to be an important determinant of human phenotypic variability, including susceptibility to complex disease. Recent studies have shown that the effects of cis-regulatory polymorphism on gene expression can differ widely between tissues. In the present study, we tested whether the effects of cis-regulatory variation can also differ between regions of the adult human brain. We used relative allelic expression to measure cis-effects on the RNA expression of five candidate genes for neuropsychiatric illness (ZNF804A, NOS1, RGS4, AKT1 and TCF4) across multiple discrete brain regions within individual subjects. For all five genes, we observed significant differences in allelic expression between brain regions in several individual subjects, suggesting regional differences in the effects of cis-regulatory polymorphism to be a common phenomenon. As well as highlighting an important caveat for studies of regulatory polymorphism in the brain, our findings indicate that it is possible to delineate brain areas in which cis-regulatory variants are active. This may provide important insights into the fundamental biology of neuropsychiatric phenotypes with which such variants are associated.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Human Molecular Genetics. - 19 : 22 (2010), p. 4490-4496. -
További szerzők:	Hill, Matthew J. Campbell, Colin D. Oladimeji, Paul B. Jeffries, Aaron R. Troakes, Claire Hortobágyi Tibor (1965-) (patológus) Williams, Brenda P. Cooper, Jonathan D. Bray, Nicholas J.
Internet cím:	Szerző által megadott URL Intézményi repozitóriumban (DEA) tárolt változat DOI
Borító:
Saját polcon:

001-es BibID:	BIBFORM051631
035-os BibID:	PMID: 23474818
Első szerző:	Vance, Caroline
Cím:	ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granules / Caroline Vance, Emma L. Scotter, Agnes L. Nishimura, Claire Troakes, Jacqueline C. Mitchell, Claudia Kathe, Hazel Urwin, Catherine Manser, Christopher C. Miller, Tibor Hortobágyi, Mike Dragunow, Boris Rogelj, Christopher E. Shaw
Dátum:	2013
ISSN:	0964-6906
Megjegyzések:	Mutations in the gene encoding Fused in Sarcoma (FUS) cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. FUS is a predominantly nuclear DNA- and RNA-binding protein that is involved in RNA processing. Large FUS-immunoreactive inclusions fill the perikaryon of surviving motor neurons of ALS patients carrying mutations at post-mortem. This sequestration of FUS is predicted to disrupt RNA processing and initiate neurodegeneration. Here, we demonstrate that C-terminal ALS mutations disrupt the nuclear localizing signal (NLS) of FUS resulting in cytoplasmic accumulation in transfected cells and patient fibroblasts. FUS mislocalization is rescued by the addition of the wild-type FUS NLS to mutant proteins. We also show that oxidative stress recruits mutant FUS to cytoplasmic stress granules where it is able to bind and sequester wild-type FUS. While FUS interacts with itself directly by protein-protein interaction, the recruitment of FUS to stress granules and interaction with PABP are RNA dependent. These findings support a two-hit hypothesis, whereby cytoplasmic mislocalization of FUS protein, followed by cellular stress, contributes to the formation of cytoplasmic aggregates that may sequester FUS, disrupt RNA processing and initiate motor neuron degeneration.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Human Molecular Genetics. - 22 : 13 (2013), p. 2676-2688. -
További szerzők:	Scotter, Emma L. Nishimura, Agnes Lumi Troakes, Claire Mitchell, Jacqueline C. Kathe, Claudia Urwin, Hazel Manser, Catherine Miller, Christopher C. Hortobágyi Tibor (1965-) (patológus) Dragunow, Mike Rogelj, Boris Shaw, Christopher E.
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: