8 research outputs found
A genome-wide association study in multiple system atrophy
Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy
(MSA), we undertook a genome-wide association study (GWAS).
Methods: We performed a GWAS with .5 million genotyped and imputed single nucleotide polymorphisms
(SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA
cases were collected from North American and European centers, one third of which were neuropathologically
confirmed.
Results: We found no significant loci after stringent multiple testing correction. A number of regions
emerged as potentially interesting for follow-up at p , 1 3 1026, including SNPs in the
genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association
of the genes SNCA and COQ2 with MSA.
Conclusions: We present a GWAS in MSA.We have identified several potentially interesting gene
loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set.
Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the
future, additional samples of well-characterized patients with MSA will need to be collected to
perform a larger MSA GWAS, but this initial study forms the basis for these next steps
Discordance between Expression and Genome Transfer Titering of HSV Amplicon Vectors: Recommendation for Standardized Enumeration
Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia
Background and Purpose - We investigated the contribution of gap junctions to brain damage and delayed neuronal death produced by oxygen-glucose deprivation (OGD). Methods - Histopathology, molecular biology, and electrophysiological and fluorescence cell death assays in slice cultures after OGD and in developing rats after intrauterine hypoxia-ischemia (HI). Results - OGD persistently increased gap junction coupling and strongly activated the apoptosis marker caspase-3 in slice cultures. The gap junction blocker carbenoxolone applied to hippocampal slice cultures before, during, or 60 minutes after OGD markedly reduced delayed neuronal death. Administration of carbenoxolone to ischemic pups immediately after intrauterine HI prevented caspase-3 activation and dramatically reduced long-term neuronal damage. Conclusions - Gap junction blockade may be a useful therapeutic tool to minimize brain damage produced by perinatal and early postnatal HI. © 2005 American Heart Association, Inc
Modules, networks and systems medicine for understanding disease and aiding diagnosis
10.1186/s13073-014-0082-6Genome Medicine6108