Mapping&lt;footref rid="foot01"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/footref&gt; of the NDUFA2, NDUFA6, NDUFA7, NDUFB8, and NDUFS8 electron transport chain genes by intron based radiation hybrid mapping

Emahazion, Tesfai; Brookes, Anthony J.

doi:10.1159/000015081

Cited by 17 publications

(8 citation statements)

References 3 publications

(4 reference statements)

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“…Three independent signals were identified. The strongest signal was on chromosome 22 in a region that includes: the cytochrome P450 gene CYP2D6 , which is linked to drug metabolism; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 6, 14 kDa ( NDUFA6 ), which is involved in mitochondrial function; 46 and septin 3 ( SEPT3 ), which is associated with Alzheimer's disease. 47 The two other regions included: SNPs in phosphodiesterase 1C, calmodulin-dependent 70 kDa ( PDE1C ), a calmodulin-dependent PDE that is stimulated by a calcium-calmodulin complex; 48 and a single SNP in Fucosyltransferase 8 (alpha (1,6) fucosyltransferase ( FUT8 ), which catalyses the transfer of fucose from GDP-fucose to N-linked type complex glycopeptides.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

et al. 2016

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People's differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal–numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31% (s.e.m.=1.8%) for verbal–numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer's disease and schizophrenia.

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Section: Resultsmentioning

confidence: 99%

Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

et al. 2016

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“…The nuclear gene encoding it is unaffected by oxidative damage to mitochondrial DNA. The NDUFA subunits are critical components involved in assembly of the holoenzyme NADH dehydrogenase complex (30). This subunit of complex I was reported previously to be particularly susceptible to inactivation by peroxynitrite (31).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Protein Nitration Primes Neurodegeneration in Experimental Autoimmune Encephalomyelitis

Qi¹,

Lewin²,

Sun³

et al. 2006

J. Biol. Chem.

123

108

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The mechanisms of axonal and neuronal degeneration causing visual and neurologic disability in multiple sclerosis are poorly understood. Here we explored the contribution of mitochondria to neurodegeneration in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis. Oxidative injury to the murine mitochondrion preceded the infiltration of inflammatory cells, classically heralded as the mediators of demyelination and axonal injury by transection. Nitration of mitochondrial proteins affected key subunits of complexes I and IV of the respiratory chain and a chaperone critical to the stabilization and translocation of proteins into the organelle. Oxidative products were associated with loss of mitochondrial membrane potential and apoptotic cell death. Reductions in the rate of synthesis of adenosine triphosphate were severe and even greater than those associated with disorders caused by mutated mitochondrial DNA. Mitochondrial vacuolization, swelling, and dissolution of cristae occurred in axons as early as 3 days after sensitization for experimental autoimmune encephalomyelitis. Our findings implicate mitochondrial dysfunction induced by protein inactivation and mediated by oxidative stress initiates a cascade of molecular events leading to apoptosis and neurodegeneration in experimental autoimmune encephalomyelitis that is not mediated by inflammatory cells.

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“…DEGs such as NDUFA2 , NDUFB8 , NDUFA7 , NDUFA1 , NDUFB1 , NDUFS7 , NDUFV1 , NDUFV2 , and NDUFS3 jointly encode subunits of nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase (complex I) ( 23 ). NADH is the entry enzyme of mitochondrial oxidative phosphorylation ( 24 ), which plays a key role in mitochondrial respiration.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling analysis of lung adenocarcinoma

et al. 2016

Braz J Med Biol Res

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The present study screened potential genes related to lung adenocarcinoma, with the aim of further understanding disease pathogenesis. The GSE2514 dataset including 20 lung adenocarcinoma and 19 adjacent normal tissue samples from 10 patients with lung adenocarcinoma aged 45-73 years was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the two groups were screened using the t-test. Potential gene functions were predicted using functional and pathway enrichment analysis, and protein-protein interaction (PPI) networks obtained from the STRING database were constructed with Cytoscape. Module analysis of PPI networks was performed through MCODE in Cytoscape. In total, 535 upregulated and 465 downregulated DEGs were identified. These included ATP5D, UQCRC2, UQCR11 and genes encoding nicotinamide adenine dinucleotide (NADH), which are mainly associated with mitochondrial ATP synthesis coupled electron transport, and which were enriched in the oxidative phosphorylation pathway. Other DEGs were associated with DNA replication (PRIM1, MCM3, and RNASEH2A), cell surface receptor-linked signal transduction and the enzyme-linked receptor protein signaling pathway (MAPK1, STAT3, RAF1, and JAK1), and regulation of the cytoskeleton and phosphatidylinositol signaling system (PIP5K1B, PIP5K1C, and PIP4K2B). Our findings suggest that DEGs encoding subunits of NADH, PRIM1, MCM3, MAPK1, STAT3, RAF1, and JAK1 might be associated with the development of lung adenocarcinoma.

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Mapping<footref rid="foot01"><sup>1</sup></footref> of the NDUFA2, NDUFA6, NDUFA7, NDUFB8, and NDUFS8 electron transport chain genes by intron based radiation hybrid mapping

Cited by 17 publications

References 3 publications

Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

Mitochondrial Protein Nitration Primes Neurodegeneration in Experimental Autoimmune Encephalomyelitis

Gene expression profiling analysis of lung adenocarcinoma

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