Home About us Contact
|
Home About us Contact | ||
|
|
||
Subunit Gene (subunit + gene)
Kinds of Subunit Gene Selected AbstractsLoss of the Potassium Channel ,-Subunit Gene, KCNAB2, Is Associated with Epilepsy in Patients with 1p36 Deletion SyndromeEPILEPSIA, Issue 9 2001Heidi A. Heilstedt Summary: ,Purpose: Clinical features associated with chromosome 1p36 deletion include characteristic craniofacial abnormalities, mental retardation, and epilepsy. The presence and severity of specific phenotypic features are likely to be correlated with loss of a distinct complement of genes in each patient. We hypothesize that hemizygous deletion of one, or a few, critical gene(s) controlling neuronal excitability is associated with the epilepsy phenotype. Because ion channels are important determinants of seizure susceptibility and the voltage-gated K+ channel ,-subunit gene, KCNAB2, has been localized to 1p36, we propose that deletion of this gene may be associated with the epilepsy phenotype. Methods: Twenty-four patients were evaluated by fluorescence in situ hybridization with a probe containing KCNAB2. Clinical details were obtained by neurologic examination and EEG. Results: Nine patients are deleted for the KCNAB2 locus, and eight (89%) of these have epilepsy or epileptiform activity on EEG. The majority of patients have a severe seizure phenotype, including infantile spasms. In contrast, of those not deleted for KCNAB2, only 27% have chronic seizures, and none had infantile spasms. Conclusions: Lack of the , subunit would be predicted to reduce K+ channel,mediated membrane repolarization and increase neuronal excitability, suggesting a possible relation between loss of this gene and the development of seizures. Because some patients with seizures were not deleted for KCNAB2, there may be additional genes within 1p36 that contribute to epilepsy in this syndrome. Hemizygosity of this gene in a majority of monosomy 1p36 syndrome patients with epilepsy suggests that haploinsufficiency for KCNAB2 is a significant risk factor for epilepsy. [source] Association of Markers in the 3, Region of the GluR5 Kainate Receptor Subunit Gene to Alcohol DependenceALCOHOLISM, Issue 5 2009Henry R. Kranzler Background:, Glutamate neurotransmission plays an important role in a variety of alcohol-related phenomena, including alcohol self-administration by both animals and humans. Because the risk for alcohol dependence (AD) is genetically influenced, genes encoding glutamate receptors are candidates to contribute to the risk for AD. We examined the role of variation in the 3, region of GRIK1, the gene that encodes the GluR5 receptor subunit of the kainic acid glutamate receptor, on risk for AD. We focused specifically on this gene because topiramate, a glutamate modulator that binds to the GluR5 subunit, has shown robust efficacy in the treatment of AD. Methods:, We genotyped 7 single nucleotide polymorphisms (SNPs) in the 3,-half of GRIK1, which includes 3 differentially spliced exons, in a sample of EA control subjects (n = 507) and subjects with AD (n = 1,057). Results:, We found nominally significant evidence of association to AD for 3 SNPs (rs2832407 in intron 9, rs2186305 in intron 17, and rs2832387 in the 3,UTR). Empirical p -value estimation revealed that only rs2832407 was significantly associated to phenotype (p = 0.043). Discussion:, These findings provide support for the hypothesis that variation in the 3, portion of the gene encoding the GluR5 kainate receptor subunit contributes to the risk for AD. Further research is needed to ascertain whether this SNP is itself functional or whether the association reflects linkage disequilibrium with functional variation elsewhere in the gene and whether this SNP moderates topiramate's effects in the treatment of AD. [source] Deletion of the ,7 Nicotinic Receptor Subunit Gene Results in Increased Sensitivity to Several Behavioral Effects Produced by AlcoholALCOHOLISM, Issue 3 2005Barbara J. Bowers Background: The finding that most people with alcoholism are also heavy smokers prompted several research groups to evaluate the effects of ethanol on neuronal nicotinic acetylcholine receptor (nAChR) function. Data collected in vitro indicate that physiologically relevant concentrations of ethanol inhibit the functional activation of homomeric ,7 nAChRs, which are one of the most abundant nAChR subtypes expressed in the mammalian brain. The studies outlined here used ,7 gene knockout (null mutant) mice to evaluate the potential role of ,7 nAChRs in modulating selected behavioral and physiological effects produced by ethanol. Methods: Current evidence indicates that many responses to ethanol are not genetically correlated. Therefore, the authors measured the effects of acute administration of ethanol on several behaviors that are altered by both ethanol and nicotine: two tests of locomotor activity, acoustic startle, prepulse inhibition of acoustic startle, and body temperature. Ethanol-induced durations of loss of righting reflex and ethanol elimination rates were also determined. These studies used null mutant (,7,/,) and wild-type (,7+/+) mice. Results: Relative to ,7+/+ mice, ,7,/, mice were more sensitive to the activating effects of ethanol on open-field activity, ethanol-induced hypothermia, and duration of loss of the righting response. Deletion of the ,7 gene did not influence the effects of ethanol on Y-maze crossing or rearing activities, acoustic startle, or prepulse inhibition of startle. Gene deletion did not alter ethanol metabolism. Conclusions: These results indicate that some but not all of the behavioral effects of ethanol are mediated in part by effects on nAChRs that include the ,7 subunit and may help to explain the robust association between alcohol consumption and the use of tobacco. [source] An Analysis Paradigm for Investigating Multi-locus Effects in Complex Disease: Examination of Three GABAA Receptor Subunit Genes on 15q11-q13 as Risk Factors for Autistic Disorder.ANNALS OF HUMAN GENETICS, Issue 3 2006A. E. Ashley-Koch Summary Gene-gene interactions are likely involved in many complex genetic disorders and new statistical approaches for detecting such interactions are needed. We propose a multi-analytic paradigm, relying on convergence of evidence across multiple analysis tools. Our paradigm tests for main and interactive effects, through allele, genotype and haplotype association. We applied our paradigm to genotype data from three GABAA receptor subunit genes (GABRB3, GABRA5, and GABRG3) on chromosome 15 in 470 Caucasian autism families. Previously implicated in autism, we hypothesized these genes interact to contribute to risk. We detected no evidence of main effects by allelic (PDT, FBAT) or genotypic (genotype-PDT) association at individual markers. However, three two-marker haplotypes in GABRG3 were significant (HBAT). We detected no significant multi-locus associations using genotype-PDT analysis or the EMDR data reduction program. However, consistent with the haplotype findings, the best single locus EMDR model selected a GABRG3 marker. Further, the best pairwise genotype-PDT result involved GABRB3 and GABRG3, and all multi-locus EMDR models also selected GABRB3 and GABRG3 markers. GABA receptor subunit genes do not significantly interact to contribute to autism risk in our overall data set. However, the consistency of results across analyses suggests that we have defined a useful framework for evaluating gene-gene interactions. [source] Ataxic mutant mice with defects in Ca2+ channel ,1A subunit gene: morphological and functional abnormalities in cerebellar cortical neuronsCONGENITAL ANOMALIES, Issue 2 2000Kazuhiko Sawada ABSTRACT This review summarizes recent studies in the morphological and functional abnormalities of cerebella in three ataxic mutant mice, i.e. tottering mouse, leaner mouse, and rolling mouse Nagoya (RMN). These mutants carry mutations in the Ca2+ channel ,1A subunit gene, and become useful models for human neurological diseases such as episodic ataxia type-2, familial hemiplegic migraine, and spinocerebellar ataxia type-6. All three mutants exhibited altered morphology of the Purkinje cells, ectopic synaptic contacts between granule cell axons (parallel fibers) and Purkinje cell dendritic spines and abnormal expression of tyrosine hydroxylase in Purkinje cells. In leaner mice, Purkinje cell loss was observed in alternating sagittal compartments of the cerebellar cortex corresponding to the Zebrin II-negative zones. The mutated Ca2+ channel ,1A subunit was highly expressed in granule and Purkinje cells, and the P-type Ca2+ currents in Purkinje cells were selectively reduced in the mutant mice. Therefore, we concluded that altered Ca2+ currents through the mutated Ca2+ channel ,1A subunit might be involved in the functional and morphological abnormalities in granule and Purkinje cells, and might result in expressions of behavioral phenotypes including ataxia. Increased levels of corticotropin-releasing factor and cholecystokinin in some climbing and mossy fibers were observed in RMN. These neuropeptides modulated the excitability of granule and Purkinje cells, indicating the possible expression of ataxic symptoms. [source] Analysis of the distribution and diversity in recent Hawaiian volcanic deposits of a putative carbon monoxide dehydrogenase large subunit geneENVIRONMENTAL MICROBIOLOGY, Issue 9 2005Kari E. Dunfield Summary A putative carbon monoxide dehydrogenase large subunit gene (BMS putative coxL) was amplified from genomic DNA extracts of four recent (42,300 year old) Hawaiian volcanic deposits by polymerase chain reaction (PCR). Sequence databases derived from clone libraries constructed using PCR products were analysed phylogenetically and statistically. These analyses indicated that each of the deposits supported distinct BMS putative coxL gene assemblages. Statistical analyses also showed that the youngest deposit (42 years old) contained the least diverse sequences (P < 0.05), but that diversity did not vary significantly among three older deposits with ages from about 108,300 years. Although diversity indices did not vary among the older deposits, mismatch analyses suggested population structures increased in complexity with increasing deposit age. At each of the sites, most of the clone sequences appeared to originate from Proteobacteria not currently represented in culture or recognized as CO oxidizers. [source] Isolation and properties of methanesulfonate-degrading Afipia felis from Antarctica and comparison with other strains of A. felisENVIRONMENTAL MICROBIOLOGY, Issue 1 2005S. Azra Moosvi Summary Three novel strains of methylotrophic Afipia felis were isolated from several locations on Signy Island, Antarctica, and a fourth from estuary sediment from the River Douro, Portugal. They were identified as strains of the ,-2 proteobacterium A. felis by 16S rRNA gene sequence, analysis., Two, strains, tested, were, shown to contain the fdxA gene, diagnostic for A. felis. All strains grew with methanesulfonate (and two strains with dimethylsulfone) as sole carbon substrate. Growth on methanesulfonate required methanesulfonate monooxygenase (MSAMO), using NADH as the reductant and stimulated by reduced flavin nucleotides and Fe(II). Polymerase chain reaction amplification of DNA from an Antarctic strain showed a typical msmA gene for the ,-hydroxylase of MSAMO, and both Antarctic and Portuguese strains contained mxaF, the methanol dehydrogenase large subunit gene. This is the first report of methanesulfonate-degrading bacteria from the Antarctic and of methylotrophy in Afipia, and the first description of any bacterium able to use both methanesulfonate and dimethylsulfone. In contrast, the type strain of A. felis DSM 7326T was not methylotrophic, but grew in defined mineral medium with a wide range of single simple organic substrates. Free-living Afipia strains occurring widely in the natural environment may be significant as methylotrophs, degrading C1 -sulfur compounds, including the recalcitrant organosulfur compound methanesulfonate. [source] Loss of the Potassium Channel ,-Subunit Gene, KCNAB2, Is Associated with Epilepsy in Patients with 1p36 Deletion SyndromeEPILEPSIA, Issue 9 2001Heidi A. Heilstedt Summary: ,Purpose: Clinical features associated with chromosome 1p36 deletion include characteristic craniofacial abnormalities, mental retardation, and epilepsy. The presence and severity of specific phenotypic features are likely to be correlated with loss of a distinct complement of genes in each patient. We hypothesize that hemizygous deletion of one, or a few, critical gene(s) controlling neuronal excitability is associated with the epilepsy phenotype. Because ion channels are important determinants of seizure susceptibility and the voltage-gated K+ channel ,-subunit gene, KCNAB2, has been localized to 1p36, we propose that deletion of this gene may be associated with the epilepsy phenotype. Methods: Twenty-four patients were evaluated by fluorescence in situ hybridization with a probe containing KCNAB2. Clinical details were obtained by neurologic examination and EEG. Results: Nine patients are deleted for the KCNAB2 locus, and eight (89%) of these have epilepsy or epileptiform activity on EEG. The majority of patients have a severe seizure phenotype, including infantile spasms. In contrast, of those not deleted for KCNAB2, only 27% have chronic seizures, and none had infantile spasms. Conclusions: Lack of the , subunit would be predicted to reduce K+ channel,mediated membrane repolarization and increase neuronal excitability, suggesting a possible relation between loss of this gene and the development of seizures. Because some patients with seizures were not deleted for KCNAB2, there may be additional genes within 1p36 that contribute to epilepsy in this syndrome. Hemizygosity of this gene in a majority of monosomy 1p36 syndrome patients with epilepsy suggests that haploinsufficiency for KCNAB2 is a significant risk factor for epilepsy. [source] Congenital myasthenic syndrome due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit geneEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2002S. Kraner No abstract is available for this article. [source] Functional (GT)n polymorphisms in promoter region of N -methyl- d -aspartate receptor 2A subunit (GRIN2A) gene affect hippocampal and amygdala volumesGENES, BRAIN AND BEHAVIOR, Issue 3 2010H. Inoue The glutamate system including N -methyl- d -aspartate (NMDA) affects synaptic formation, plasticity and maintenance. Recent studies have shown a variable (GT)n polymorphism in the promoter region of the NMDA subunit gene (GRIN2A) and a length-dependent inhibition of transcriptional activity by the (GT)n repeat. In the present study, we examined whether the GRIN2A polymorphism is associated with regional brain volume especially in medial temporal lobe structures, in which the NMDA-dependent synaptic processes have been most extensively studied. Gray matter regions of interest (ROIs) for the bilateral amygdala and hippocampus were outlined manually on the magnetic resonance images of 144 healthy individuals. In addition, voxel-based morphometry (VBM) was conducted to explore the association of genotype with regional gray matter volume from everywhere in the brain in the same sample. The manually measured hippocampal and amygdala volumes were significantly larger in subjects with short allele carriers (n = 89) than in those with homozygous long alleles (n = 55) when individual differences in intracranial volume were accounted for. The VBM showed no significant association between the genotype and regional gray matter volume in any brain region. These findings suggest that the functional GRIN2A (GT)n polymorphism could weakly but significantly impact on human medial temporal lobe volume in a length-dependent manner, providing in vivo evidence of the role of the NMDA receptor in human brain development. [source] Fine mapping of a sedative-hypnotic drug withdrawal locus on mouse chromosome 11GENES, BRAIN AND BEHAVIOR, Issue 1 2006H. M. Hood We have established that there is a considerable amount of common genetic influence on physiological dependence and associated withdrawal from sedative-hypnotic drugs including alcohol, benzodiazepines, barbiturates and inhalants. We previously mapped two loci responsible for 12 and 9% of the genetic variance in acute alcohol and pentobarbital withdrawal convulsion liability in mice, respectively, to an approximately 28-cM interval of proximal chromosome 11. Here, we narrow the position of these two loci to a 3-cM interval (8.8 Mb, containing 34 known and predicted genes) using haplotype analysis. These include genes encoding four subunits of the GABAA receptor, which is implicated as a pivotal component in sedative-hypnotic dependence and withdrawal. We report that the DBA/2J mouse strain, which exhibits severe withdrawal from sedative-hypnotic drugs, encodes a unique GABAA receptor ,2 subunit variant compared with other standard inbred strains including the genetically similar DBA/1J strain. We also demonstrate that withdrawal from zolpidem, a benzodiazepine receptor agonist selective for ,1 subunit containing GABAA receptors, is influenced by a chromosome 11 locus, suggesting that the same locus (gene) influences risk of alcohol, benzodiazepine and barbiturate withdrawal. Our results, together with recent knockout studies, point to the GABAA receptor ,2 subunit gene (Gabrg2) as a promising candidate gene to underlie phenotypic differences in sedative-hypnotic physiological dependence and associated withdrawal episodes. [source] Microdeletions involving the SCN1A gene may be common in SCN1A -mutation-negative SMEI patients,HUMAN MUTATION, Issue 9 2006Arvid Suls Abstract Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome is a rare epilepsy syndrome. In 30 to 70% of SMEI patients, truncating and missense mutations in the neuronal voltage-gated sodium-channel ,-subunit gene (SCN1A) have been identified. The majority of patients have truncating mutations that are predicted to be loss-of-function alleles. Because mutation detection studies use PCR-based sequencing or conformation sensitive gel electrophoresis (CSGE), microdeletions, which are also predicted to be loss-of-function alleles, can easily escape detection. We selected 11 SMEI patients with or without additional features who had no SCN1A mutation detectable with sequencing analysis. In addition, none of the patients was heterozygous for any of the SNPs in SCN1A, indicating that they were either homozygous for all SNPs or hemizygous due to a microdeletion of the gene. We subsequently analyzed these patients for the presence of microdeletions in SCN1A using a quantitative PCR method named multiplex amplicon quantification (MAQ), and observed three patients missing one copy of the SCN1A gene. All three microdeletions were confirmed by fluorescence in situ hybridization (FISH). These findings demonstrate that a substantial percentage of SCN1A -mutation-negative SMEI patients with or without additional features carry a chromosomal microdeletion comprising the SCN1A gene and that haploinsufficiency of the SCN1A gene is a cause of SMEI. Hum Mutat 27(9), 914,920, 2006. © 2006 Wiley-Liss, Inc. [source] Evaluation of an automated screening assay for von Willebrand Disease Type 2NINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2002S. L. Taylor Summary Evaluating the factor VIII (FVIII) binding activity of von Willebrand factor (VWF) is an important step in the diagnostic work-up of families affected by apparent mild haemophilia A. In von Willebrand's disease (VWD) type 2N (Normandy), mutations at the N-terminal end of the mature VWF subunit gene prevent the binding of FVIII. Individuals heterozygous for type 2N VWD are generally asymptomatic. Homozygotes and compound heterozygotes present with a clinical picture which mimics haemophilia A, with a markedly reduced FVIII : C activity and VWF within the normal range, but instead of exhibiting X-linked inheritance they show an autosomal recessive inheritance pattern. The distinction between haemophilia A and VWD type 2N has important implications for therapy and genetic counselling. We present a highly specific enzyme-linked immunosorbent assay screening method for the Normandy variant, which measures VWF : FVIII binding activity in parallel with VWF antigen, using monoclonal capture and detection antibodies. The assay is fully automated using a robotic microtitre plate processor, requiring minimal user intervention and providing the capacity to screen large numbers of patients. [source] Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegansAGING CELL, Issue 3 2010Wen Yang Summary In Caenorhabditis elegans, longevity is increased by a partial loss-of-function mutation in the mitochondrial complex III subunit gene isp-1. Longevity is also increased by RNAi against the expression of a variety of mitochondrial respiratory chain genes, including isp-1, but it is unknown whether the isp-1(qm150) mutation and the RNAi treatments trigger the same underlying mechanisms of longevity. We have identified nuo-6(qm200), a mutation in a conserved subunit of mitochondrial complex I (NUDFB4). The mutation reduces the function of complex I and, like isp-1(qm150), results in low oxygen consumption, slow growth, slow behavior, and increased lifespan. We have compared the phenotypes of nuo-6(qm200) to those of nuo-6(RNAi) and found them to be distinct in crucial ways, including patterns of growth and fertility, behavioral rates, oxygen consumption, ATP levels, autophagy, and resistance to paraquat, as well as expression of superoxide dismutases, mitochondrial heat-shock proteins, and other gene expression markers. RNAi treatments appear to generate a stress and autophagy response, while the genomic mutation alters electron transport and reactive oxygen species metabolism. For many phenotypes, we also compared isp-1(qm150) to isp-1(RNAi) and found the same pattern of differences. Most importantly, we found that, while the lifespan of nuo-6, isp-1 double mutants is not greater than that of the single mutants, the lifespan increase induced by nuo-6(RNAi) is fully additive to that induced by isp-1(qm150), and the increase induced by isp-1(RNAi) is fully additive to that induced by nuo-6(qm200). Our results demonstrate that distinct and separable aspects of mitochondrial biology affect lifespan independently. [source] Variation in enterovirus receptor genesJOURNAL OF MEDICAL VIROLOGY, Issue 1 2003Åse Karttunen Abstract The increased incidence of a enterovirus infections observed in patients with type 1 diabetes preceding the development of the clinical disease could be partially explained by variation in the genes coding for enterovirus receptors. We carried out sequence analysis of the most common enterovirus receptor molecules in 21 diabetic children and 20 healthy adults. DNA was isolated from the leukocytes, and gene regions known to code for virus-recognizing domains in major enterovirus receptors were amplified and sequenced. Heterozygous single-nucleotide polymorphism (SNP), Ala 67 (GCG),,,Thr (ACG), was detected in the poliovirus receptor gene in four individuals in the diabetes group, but not in the control group. However, serological studies could not confirm that this substitution would convey different susceptibility to poliovirus infection. A heterozygous SNP, Lys 29 (AAG),,,Met (ATG), was found in the intracellular adhesion molecule-1 (ICAM-1) (receptor for rhinoviruses and some coxsackie A viruses) in one individual in both groups. A silent SNP in the ,2 integrin subunit gene (echovirus 1 receptor) was frequently found in both groups, a silent heterozygotic SNP in coxsackievirus-adenovirus receptor (coxsackie B virus receptor) gene was seen in one individual in the diabetes group, whereas no variation was found in the DAF (echovirus receptor) and ,3 integrin subunit sequences (receptor for coxsackievirus A9) studied. In conclusion, both synonymous and nonsynonymous sequence variability of genes coding for enterovirus and rhinovirus receptors was shown to occur, but no pattern directly specific for type 1 diabetes was found. J. Med. Virol. 70:99,108, 2003. © 2003 Wiley-Liss, Inc. [source] Nicotinic ,5 subunit deletion locally reduces high-affinity agonist activation without altering nicotinic receptor numbersJOURNAL OF NEUROCHEMISTRY, Issue 1 2007Robert W. B. Brown Abstract Neuronal nicotinic acetylcholine receptor subunit ,5 mRNA is widely expressed in the CNS. An ,5 gene polymorphism has been implicated in behavioral differences between mouse strains, and ,5-null mutation induces profound changes in mouse acute responses to nicotine. In this study, we have examined the distribution and prevalence of ,5* nicotinic acetylcholine receptor in mouse brain, and quantified the effects of ,5-null mutation on pre-synaptic nicotinic acetylcholine receptor function (measured using synaptosomal 86Rb+ efflux) and overall [125I]epibatidine binding site expression. ,5* nicotinic acetylcholine receptor expression was found in nine of fifteen regions examined, although < 20% of the total nicotinic acetylcholine receptor population in any region contained ,5. Deletion of the ,5 subunit gene resulted in localized loss of function (thalamus, striatum), which was itself confined to the DH,E-sensitive receptor population. No changes in receptor expression were seen. Consequently, functional changes must occur as a result of altered function per unit of receptor. The selective depletion of high agonist activation affinity sites results in overall nicotinic function being reduced, and increases the overall agonist activation affinity. Together, these results describe the receptor-level changes underlying altered behavioral responses to nicotine in nicotinic acetylcholine receptor ,5 subunit-null mutants. [source] SYNTHESIS OF MOLECULAR RESEARCH ON BATRACHOSPERMUM HELMINTHOSUM (RHODOPHYTA) FROM STREAM REACHES IN EASTERN NORTH AMERICAJOURNAL OF PHYCOLOGY, Issue 2001Article first published online: 24 SEP 200 Vis, M. L., Hall, M. M., Machesky, N. J. & Miller, E. J. Department of Environmental and Plant Biology, Ohio University, Athens, OH 45701 USA The freshwater red alga Batrachospermum helminthosum was collected from eleven streams throughout the species range in eastern North America as follows: three stream reaches from Ohio, and one each from Michigan, Indiana, Tennessee, Louisiana, North Carolina, Connecticut, Rhode Island and Massachusetts. The molecular marker technique of inter-simple sequence repeats (ISSR) and sequence data from the plastid encoded rubisco large subunit gene (rbcL), the mitochondrial COX2-COX3 gene spacer region, and the nuclear region of ITS1-5.8S rDNA-ITS2 were employed to examine biogeographic trends in this alga. Analysis of the rbcL sequence revealed 5 genotypes with one genotype representing individuals from seven stream reaches. Data from the ISSR molecular markers gave a distinct banding pattern for each of 165 individuals examined. ISSR results showed all individuals within a reach clustered together but did not provide well-defined groupings based on stream reach. The sequence data for the COX2-COX3 gene spacer was invariant among individuals from a stream reach. The individuals from Connecticut, Rhode Island and 2 Ohio stream reaches were identical and similarly the individuals from the North Carolina and another Ohio location did not vary in sequence so that seven genotypes were recorded among the individuals from the eleven stream reaches. Analysis of the ITS1-5.8S rDNA-ITS2 region showed sequence variation not only among individuals from different streams but also among individuals from the same reach. The utility and congruency of these data sets to answer biogeographic questions will be discussed. [source] Hormonal control of somatic cell oocyte interactions during ovarian follicle development,MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2004Catherine M.H. Combelles Abstract In the mammalian ovarian follicle, paracrine signaling between the oocyte and somatic granulosa cells is bidirectional but the structural basis and physiological regulations of communication between gametic and somatic compartments remain unknown. The present experiments were designed to test the hypothesis that follicle stimulating hormone (FSH) regulates the ability of granulosa cells to make connections with the oocyte. We show that in prepubertal unprimed mice and mice carrying a targeted deletion of the FSH, subunit gene, granulosa cells exhibit orientation towards the oocyte manifest by the elaboration of transzonal projections (TZPs) and "apical" centrosome positioning at sites of granulosa-zona contact. In vivo FSH treatment results in a retraction of TZPs. Coincident with TZP retraction induced by FSH are changes in oocyte transcriptional activity and meiotic competence, which suggests one means by which the oocyte-granulosa cell dialogue may be modulated during development of ovarian follicles. Mol. Reprod. Dev. 69: 347,355, 2004. © 2004 Wiley-Liss, Inc. [source] Identification of a de novo Lys304Gln mutation in the glycine receptor ,-1 subunit gene in a Korean infant with hyperekplexiaMOVEMENT DISORDERS, Issue 4 2008Hoon-Chul Kang MD Abstract Startle disease or hyperekplexia (STHE; MIM 149400) is a rare disorder that is characterized by marked muscular hypertonia in infancy and an exaggerated startle response to unexpected acoustic or tactile stimuli. Mutations in the gene encoding the ,-1 subunit of the inhibitory glycine receptor (GLRA1) were reported as causes of STHE. Recently, we encountered a Korean male infant with generalized stiffness that was observed from the first 3 days of life. The abnormal startle response was evident from the fourth week of life, and he showed marked improvement in the startle response and muscle hypertonia after being administered phenobarbital and clonazepam. Direct sequencing analysis of the infant and his parents revealed a de novo variation (c.910A>C) in the GLRA1 gene, resulting in a novel Lys304Gln missense mutation. © 2007 Movement Disorder Society [source] ATP1A3 mutation in the first asian case of rapid-onset dystonia-parkinsonismMOVEMENT DISORDERS, Issue 12 2007Jee-Young Lee MD Abstract We report a 38-year-old Korean man with sporadic rapid-onset dystonia-parkinsonism (RDP), who had a Thr 618 Met mutation in the Na+/K+ -ATPase ,3 subunit gene (ATP1A3). At the age of 21, he acutely developed severe dystonia and parkinsonism, which rapidly deteriorated into a wheelchair-bound state within 4 days. He is the first Asian RDP patient confirmed by genetic testing, ascertaining that RDP gene mutation is present in Asians. Pathophysiological considerations are briefly discussed. © 2007 Movement Disorder Society [source] Genetic diversity of the arbuscular mycorrhizal fungus Glomus intraradices as determined by mitochondrial large subunit rRNA gene sequences is considerably higher than previously expectedNEW PHYTOLOGIST, Issue 2 2008Boris Börstler Summary ,,Glomus intraradices is a widespread arbuscular mycorrhizal fungus (AMF), which has been found in an extremely broad range of habitats, indicating a high tolerance for environmental factors and a generalist life history strategy. Despite this ecological versatility, not much is known about the genetic diversity of this fungal species across different habitats or over large geographic scales. ,,A nested polymerase chain reaction (PCR) approach for the mitochondrial rRNA large subunit gene (mtLSU), distinguished different haplotypes among cultivated isolates of G. intraradices and within mycorrhizal root samples from the field. ,,From analysis of 16 isolates of this species originating from five continents, 12 mitochondrial haplotypes were distinguished. Five additional mtLSU haplotypes were detected in field-collected mycorrhizal roots. Some introns in the mtLSU region appear to be stable over years of cultivation and are ancestral to the G. intraradices clade. ,,Genetic diversity within G. intraradices is substantially higher than previously thought, although some mtLSU haplotypes are widespread. A restriction fragment length polymorphism approach also was developed to distinguish mtLSU haplotypes without sequencing. Using this molecular tool, intraspecific genetic variation of an AMF species can be studied directly in field plants. [source] Overexpression of bacterial catalase in tomato leaf chloroplasts enhances photo-oxidative stress tolerancePLANT CELL & ENVIRONMENT, Issue 12 2003E.-A. MOHAMED ABSTRACT The Escherichia coli gene katE, which is driven by the promoter of the Rubisco small subunit gene of tomato, rbcS3C, was introduced into a tomato (Lycopersicon esculentum Mill.) by Agrobacterium tumefaciens -mediated transformation. Catalase activity in progeny from transgenic plants was approximately three-fold higher than that in wild-type plants. Leaf discs from transgenic plants remained green at 24 h after treatment with 1 µm paraquat under moderate light intensity, whereas leaf discs from wild-type plants showed severe bleaching after the same treatment. Moreover, ion leakage from transgenic leaf discs was significantly less than that from wild-type leaf discs at 24 h after treatment with 1 µm paraquat and 10 mm H2O2, respectively, under moderate light intensity. To evaluate the efficiency of the E. coli catalase to protect the whole transgenic plant from the oxidative stress, transgenic and wild-type plants were sprayed with 100 µm paraquat and exposed to high light illumination (800 µmol m,2 s,1). After 24 h, the leaves of the transgenic plants were less damaged than the leaves of the wild-type plants. The catalase activity and the photosynthesis activity (indicated by the Fv/Fm ratio) were less affected by paraquat treatment in leaves of transgenic plants, whereas the activities of the chloroplastic ascorbate peroxidase isoenzymes and the ascorbate content decreased in both lines. In addition, the transgenic plants showed increased tolerance to the oxidative damage (decrease of the CO2 fixation and photosystem II activity and increase of the lipid peroxidation) caused by drought stress or chilling stress (4 °C) under high light intensity (1000 µmol m,2 s,1). These results indicate that the expression of the catalase in chloroplasts has a positive effect on the protection of the transgenic plants from the photo-oxidative stress invoked by paraquat treatment, drought stress and chilling stress. [source] Comparative proteomic and transcriptional profiling of a bread wheat cultivar and its derived transgenic line overexpressing a low molecular weight glutenin subunit gene in the endospermPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 14 2008Federico Scossa Abstract We carried out a parallel transcriptional and proteomic comparison of seeds from a transformed bread wheat line that overexpresses a transgenic low molecular weight glutenin subunit gene relative to the corresponding nontransformed genotype. Proteomic analyses showed that, during seed development, several classes of endosperm proteins were differentially accumulated in the transformed endosperm. As a result of the strong increase in the amount of the transgenic protein, the endogenous glutenin subunit, all subclasses of gliadins, and metabolic as well as chloroform/methanol soluble proteins were diminished in the transgenic genotype. The differential accumulation detected by proteomic analyses, both in mature and developing seeds, was paralleled by the corresponding changes in transcript levels detected by microarray experiments. Our results suggest that the most evident effect of the strong overexpression of the transgenic glutenin gene consists in a global compensatory response involving a significant decrease in the amounts of polypeptides belonging to the prolamin superfamily. It is likely that such compensation is a consequence of the diversion of amino acid reserves and translation machinery to the synthesis of the transgenic glutenin subunit. [source] G Protein ,3 Subunit Gene Variants and Essential Hypertension in the Northern Chinese Han PopulationANNALS OF HUMAN GENETICS, Issue 4 2005Biao Li Summary Recently a novel C825T polymorphism in the G protein ,3 subunit gene was identified that showed an association with hypertension in a German population; the results of studies in other populations have been inconsistent. To examine the contribution of GNB3 polymorphisms to the development of hypertension in the northern Chinese Han population, we conducted a case-control study consisting of 501 hypertensive cases and 503 controls using the G(-350)A, C825T and C1429T polymorphisms. Genotypes of samples were determined by PCR and restriction digestion. Single locus analysis showed a significant association between G(-350)A and hypertension (P = 0.01) but no association for C825T or C1429T. The three polymorphisms were in tight linkage disequilibrium (D,=,1 for G(-350)A-C825T, D,= 0.92 for C825T-C1429T) and a total of 7 haplotypes were observed in the entire population. Haplotype A-C-C was found to be significantly related to hypertension (P = 0.032) and A-C-C carriers had a more than two-fold higher risk of hypertension than non-carriers, after adjustment for BMI and glucose. In conclusion, our study suggests that G(-350)A is a potential functional polymorphism that may be related to hypertension, whereas the C825T and C1429T polymorphisms are not associated with hypertension in the northern Chinese Han population. [source] Widespread distribution of knockdown resistance mutations in the bed bug, Cimex lectularius (Hemiptera: Cimicidae), populations in the United StatesARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 4 2010Fang Zhu Abstract We previously reported high deltamethrin resistance in bed bugs, Cimex lectularius, collected from multiple areas of the United States (Romero et al., 2007). Recently, two mutations, the Valine to Leucine mutation (V419L) and the Leucine to Isoleucine mutation (L925I) in voltage-gated sodium channel ,-subunit gene, had been identified to be responsible for knockdown resistance (kdr) to deltamethrin in bed bugs collected from New York (Yoon et al., 2008). The current study was undertaken to investigate the distribution of these two kdr mutations in 110 bed bug populations collected in the United States. Out of the 17 bed bug populations that were assayed for deltamethrin susceptibility, two resistant populations collected in the Cincinnati area and three deltamethrin-susceptible lab colonies showed neither of the two reported mutations (haplotype A). The remaining 12 populations contained L925I or both V419L and L925I mutations in voltage-gated sodium channel ,-subunit gene (haplotypes B&C). In 93 populations that were not assayed for deltamethrin susceptibility, 12 contained neither of the two mutations (haplotype A) and 81 contained L925I or V419L or both mutations (haplotypes B-D). Thus, 88% of the bed bug populations collected showed target-site mutations. These data suggest that deltamethrin resistance conferred by target-site insensitivity of sodium channel is widely spread in bed bug populations across the United States. © 2010 Wiley Periodicals, Inc. [source] Molecular Diversity Of Vascular Potassium Channel IsoformsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2002Victoria P Korovkina SUMMARY 1. One essential role for potassium channels in vascular smooth muscle is to buffer cell excitation and counteract vasoconstrictive influences. Several molecular mechanisms regulate potassium channel function. The interaction of these mechanisms may be one method for fine-tuning potassium channel activity in response to various physiological and pathological challenges. 2. The most prevalent K+ channels in vascular smooth muscle are large-conductance calcium- and voltage-sensitive channels (maxi-K channels) and voltage-gated channels (Kv channels). Both channel types are complex molecular structures consisting of a pore-forming , -subunit and an ancillary , -subunit. The maxi-K and Kv channel , -subunits assemble as tetramers and have S4 transmembrane domains that represent the putative voltage sensor. While most vascular smooth muscle cells identified to date contain both maxi-K and Kv channels, the expression of individual , -subunit isoforms and , -subunit association occurs in a tissue-specific manner, thereby providing functional specificity. 3. The maxi-K channel , -subunit derives its molecular diversity by alternative splicing of a single-gene transcript to yield multiple isoforms that differ in their sensitivity to intracellular Ca2+ and voltage, cell surface expression and post- translational modification. The ability of this channel to assemble as a homo- or heterotetramer allows for fine-tuning control to intracellular regulators. Another level of diversity for this channel is in its association with accessory , -subunits. Multiple , -subunits have been identified that can arise either from separate genes or alternative splicing of a , -subunit gene. The maxi-K channel , -subunits modulate the channel's Ca2+ and voltage sensitivity and kinetic and pharmacological properties. 4. The Kv channel , -subunit derives its diverse nature by the expression of several genes. Similar to the maxi-K channel, this channel has been shown to assemble as a homo- and heterotetramer, which can significantly change the Kv current phenotype in a given cell type. Association with a number of the ancillary , -subunits affects Kv channel function in several ways. Beta-subunits can induce inactivating properties and act as chaperones, thereby regulating channel cell-surface expression and current kinetics. [source] Vanishing white matter disease: A review with focus on its geneticsDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2006Jan C. Pronk Abstract Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive brain disorder, most often with a childhood onset. Magnetic resonance imaging and spectroscopy indicate that, with time, increasing amounts of cerebral white matter vanish and are replaced by fluid. Autopsy confirms white matter rarefaction and cystic degeneration. The process of localization and identification of the first two genes related to VWM, EIF2B5 and EIF2B2, was facilitated by two founder effects in the Dutch population. EIF2B5 and EIF2B2 encode the , and , subunits of translation initiation factor eIF2B. Soon it was shown that mutations in all five eIF2B subunit genes can cause VWM. EIF2B is essential for the initiation of translation of RNA into protein and is involved in regulation of the process, especially under stress conditions, which may explain the sensitivity to stress conditions observed in VWM patients. The pathophysiology of the disease is still poorly understood. MRDD Research Reviews 2006;12:123,128. © 2006 Wiley-Liss, Inc. [source] Differential expression of Na,K-ATPase , and , subunit genes in the developing zebrafish inner earDEVELOPMENTAL DYNAMICS, Issue 3 2003Brian Blasiole Abstract We have used whole-mount in situ hybridization to analyze Na,K-ATPase , and , subunit gene expression in the developing zebrafish ear. Four ,1-like (,1a.1, ,1a.2, ,1a.4, and ,1a.5) and two , (,1a and ,2b) subunit genes are expressed in ear beginning at mid-somitogenesis. Each gene exhibits a distinct spatial and temporal expression pattern. The ,1a.1 gene was ubiquitously expressed in the otic epithelium from mid-somitogenesis to 24 hr postfertilization (hpf). Expression of this gene was gradually reduced and by 48 hpf, ,1a.1 transcripts were no longer detectable in the ear. The ,1a.2 and ,1a.5 genes were expressed in regions that correspond to the anterior macula, lateral crista, and semicircular canal projections up to 48 hpf. At later stages, expression of these genes was limited to cells in the dorsolateral septum and semicircular canal projections. ,1a.4 and ,1a transcripts were ubiquitously expressed during ear development and were present in most otic tissues at 5 days postfertilization (dpf). Expression of the ,2b gene, on the other hand, was restricted to subsets of cells that form sensory epithelia. These results strongly suggest different functional roles for individual Na,K-ATPase genes in zebrafish ear development. Na,K-ATPase genes are likely to represent useful markers for the analysis of zebrafish otogenesis. Development Dynamics, 2003. © 2003 Wiley-Liss, Inc. [source] A New Chrna4 Mutation with Low Penetrance in Nocturnal Frontal Lobe EpilepsyEPILEPSIA, Issue 7 2003Tobias Leniger Summary: Purpose: To identify and characterize the mutation(s) causing nocturnal frontal lobe epilepsy in a German extended family. Methods: Neuronal nicotinic acetylcholine receptor (nAChR) subunit genes were screened by direct sequencing. Once a CHRNA4 mutation was identified, its biophysical and pharmacologic properties were characterized by expression experiments in Xenopus oocytes. Results: We report a new CHRNA4 mutation, causing a ,4-T265I amino acid exchange at the extracellular end of the second transmembrane domain (TM). Functional studies of ,4-T265I revealed an increased ACh sensitivity of the mutated receptors. ,4-T265I is associated with an unusual low penetrance of the epilepsy phenotype. Sequencing of the TM1-TM3 parts of the 1 known nAChR subunits did not support a two-locus model involving a second nAChR sequence variation. Conclusions: nAChR mutations found in familial epilepsy are not always associated with an autosomal dominant mode of inheritance. ,4-T265I is the first nAChR allele showing a markedly reduced penetrance consistent with a major gene effect. The low penetrance of the mutation is probably caused by unknown genetic or environmental factors or both. [source] Atrial Fibrillation in the Goat Induces Changes in Monophasic Action Potential and mRNA Expression of Ion Channels Involved in RepolarizationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2000HUUB M.W. VAN DER VELDEN PH.D. MAP Changes and Ion Channel Expression in Goat AF. Introduction: Sustained atrial fibrillation (AF) is characterized by a marked shortening of the atrial effective refractory period (AKRP) and a decrease or reversal of its physiolonic adaptation to heart rate. The aim of the present study was to investigate whether the AF-induced changes in AKKP in the goat are associated with changes in the atrial monophasic action potential (MAP) and whether an abnormal expression of specific ion channels underlies such changes. Methods and Results: Following thoracotomy, MAPs were recorded from the free wall of the right atrium hoth before induction of AF (control) and after cardioversion of sustained AF (>2 months) in chronically instrumented goats. In control goats. MAP duration at 80% repolarization (MAPD80) shortened (P < 0.01) from 132 ± 4 msec during slow pacing (400-msec interval) to 86 ± 10 msec during fast pacing (180 msec). After cardioversion of sustained AF, the MAPD80, during slow pacing was as short as 67 ± 5 msec (electrical remodeling). Increasing the pacing rate resulted in prolongation (P = 0.02) of the MAPD80 to 91 ± 6 msec. Also. MAPD20 (20% repolarization) shortened (P = 0.05) from 32 ± 4 msec (400 msec) to 14 ± 7 msec (180 msec) in the control goats, whereas it prolonged (P = 0.03) from 20 ± 3 msec (400 msec) to 33 ± 5 msec (180 msec) in sustained AF, mRNA expression of the L-type Ca2+ channel ,1c gene and Kv1.5 potassium channel gene, which underlie Ica, and Ikur respectively, was reduced in sustained.AF compared with sinus rhythm hy 32% (P = 0.01) and 45% (P < 0.01). respectively. No significant changes were found in the mRNA levels of the rapid Na+ channel, the Na+/Ca2+ exchanger, or the Kv4.2/4.3 channels responsible for I10. Conclusion: AF-induced electrical remodeling in the goat comprises shortening of MAPD and reversal of its physiologic rate adaptation. Changes in the time course of reploarization of the action potential are associated with changes in mRNA expression of the , subunit genes of the L.-type Ca2+ channel and the Kvl.5 potassium channel. [source] | |||||||||||||||||||||||||||||||