RESUMEN
Forest stand segmentation is a critical process for forest management and inventory. The forest stand segmentation accuracy will determine the forest stand level parameters quality. In this study, we developed an automatic forest stand segmentation algorithm based on ArboLiDAR, a software used to process Light Detection and Ranging (LiDAR) point cloud data. We then optimized the parameters for the algorithm to the Dayekou forest area on Qilian Mountain in China to find the most suitable parameters for automatic stand segmentation. Further, we extracting the forest parameters at the stand level based on Bysh method. Our results showed that the limited region growing method based on the gradient is the most suitable one for analyzing automatic stand segmentation in the studied area. Among our tested parameters groups, the fifth group contains the optimal parameters for the studied area. In addition, for forest parameters, the R2 of mean height (H), average diameter at breast height (D), basal area (G), and Stand volume (V) is 0.744, 0.720, 0.562, 0.696, respectively. The RMSE value is 5.24%, 28.57%, 19.93%, and 17.66%, respectively. Our study serves as a technical basis and reference for future studies that perform more efficient analyses on forest resource inventory in China.
RESUMEN
OBJECTIVE: To detect potential mutation in a large Chinese pedigree affected with congenital corneal dystrophy. METHODS: Two patients from the pedigree were subjected to whole exome sequencing to determine the candidate gene. Suspected mutation was verified in 13 additional members by directional Sanger sequencing. Ccorrelation between genotype and phenotype was explored. RESULTS: A missense mutation, c.1877A>C (p.His626Pro), was detected in exon 14 of the TGFBI gene in 8 patients from the pedigree, but not in five unaffected members and 100 unrelated healthy controls. Respectively, the mutation was predicted as "affecting protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and MutationTaster. CONCLUSION: The c.1877A>C mutation of the TGFBI gene probably underlies the disease in this pedigree.
Asunto(s)
Distrofias Hereditarias de la Córnea/genética , Proteínas de la Matriz Extracelular/genética , Factor de Crecimiento Transformador beta/genética , Adulto , Pueblo Asiatico/genética , Secuencia de Bases , China , Distrofias Hereditarias de la Córnea/metabolismo , Análisis Mutacional de ADN , Exones , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación , Linaje , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Congenital aniridia is a genetic disorder that manifests as iris hypoplasia and other associated ocular complications. Mutations in the paired box 6 (PAX6) gene are considered the major cause of aniridia. In this study, we identified four mutations exclusively presented in aniridia patients from a four-generation Chinese pedigree, including two single nucleotide substitutions in the 3'UTR of PAX6 (NM_000280.4:c.[*76G>A; *2977C>A]) and two missense mutations in tripartite motif containing 44 (TRIM44, NM_017583.4:c.[191C>A; 463G>A]), which lead to amino acid changes p.S64Y and p.G155R, respectively. Bioinformatic analyses revealed that the two 3'UTR mutations of PAX6 disrupted microRNA binding motifs in the wildtype 3'UTR sequence. Luciferase reporter assay and Western blotting with predicted microRNAs showed that the two 3'UTR mutations could only increase or have no effect on the expression of PAX6. Therefore, they would not be the cause of aniridia that resulted from PAX6 deficiency. Instead, we found that overexpression of TRIM44 significantly reduced the expression of PAX6 in human lens epithelial cells, and the p.G155R mutant exhibited much stronger effect than the wildtype form. We conclude that inhibition of PAX6 expression by mutant TRIM44 is a novel pathogenic mechanism for aniridia.
Asunto(s)
Aniridia/genética , Proteínas Portadoras/genética , Proteínas del Ojo/genética , Expresión Génica , Estudios de Asociación Genética , Variación Genética , Proteínas de Homeodominio/genética , Factores de Transcripción Paired Box/genética , Proteínas Represoras/genética , Regiones no Traducidas 3' , Aniridia/diagnóstico , Proteínas Portadoras/química , Biología Computacional/métodos , Femenino , Ligamiento Genético , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Repeticiones de Microsatélite , Mutación , Factor de Transcripción PAX6 , Linaje , Fenotipo , Proteínas de Motivos TripartitosRESUMEN
Brachydactyly type A2 (BDA2, MIM 112600) is characterized by the deviation and shortening of the middle phalange of the index finger and the second toe. Using genome-wide linkage analysis in a Chinese BDA2 family, we mapped the maximum candidate interval of BDA2 to a â¼1.5 Mb region between D20S194 and D20S115 within chromosome 20p12.3 and found that the pairwise logarithm of the odds score was highest for marker D20S156 (Zmaxâ=â6.09 at θâ=â0). Based on functional and positional perspectives, the bone morphogenetic protein 2 (BMP2) gene was identified as the causal gene for BDA2 in this region, even though no point mutation was detected in BMP2. Through further investigation, we identified a 4,671 bp (Chr20: 6,809,218-6,813,888) genomic duplication downstream of BMP2. This duplication was located within the linked region, co-segregated with the BDA2 phenotype in this family, and was not found in the unaffected family members and the unrelated control individuals. Compared with the previously reported duplications, the duplication in this family has a different breakpoint flanked by the microhomologous sequence GATCA and a slightly different length. Some other microhomologous nucleotides were also found in the duplicated region. In summary, our findings support the conclusions that BMP2 is the causing gene for BDA2, that the genomic location corresponding to the duplication region is prone to structural changes associated with malformation of the digits, and that this tendency is probably caused by the abundance of microhomologous sequences in the region.
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Pueblo Asiatico/genética , Proteína Morfogenética Ósea 2/genética , Braquidactilia/genética , Duplicación de Gen , Linaje , Secuencia de Bases , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/genética , Puntos de Rotura del Cromosoma , Femenino , Factor 5 de Diferenciación de Crecimiento/genética , Humanos , Masculino , FenotipoRESUMEN
BACKGROUND: Allicin is the main active constituent of Allium sativum L., which is characterized by broad antibacterial spectrum (MarkosN et al., 2008; Chen et al., 2008); it also has apparent inhibitory effects on a variety of tumors. The Objective of the paper is to study the inhibitory effect of allicin on human gastric cancer cell line SGC-7901. MATERIALS AND METHODS: MTT assay and flow cytometry technique were applied to determine the inhibition rate of allicin on human gastric cancer cell line SGC-7901. The results shows that different concentrations of allicin apparently inhibited the gastric cancer SGC7901 cells, cell growth inhibition rates in the experimental groups showed an upward trend with increased allicin concentration, which were concentration-dependent. RESULTS: Flow cytometry results found that the cell cycle was arrested in the G2/M phase. Allicin has an apparent inhibitory effect on proliferation of gastric cancer cells, and can induce their apoptosis. CONCLUSION: Compared with other chemotherapeutic drugs, allicin's anti-tumor effect is better; and toxic and side effects are relatively small.
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Allium/química , Antineoplásicos Fitogénicos/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Ácidos Sulfínicos/uso terapéutico , Antineoplásicos Fitogénicos/farmacología , Apoptosis , División Celular , Línea Celular Tumoral , Disulfuros , Humanos , Extractos Vegetales/farmacología , Ácidos Sulfínicos/farmacologíaRESUMEN
BACKGROUND: Congenital cataract is a Mendelian disorder that frequently causes blindness in infants. To date, various cataract-associated loci have been mapped; more than 30 genes have been identified by linkage analysis. However, the pathogenic loci in some affected families are still unknown, and new research strategies are needed. In this study, we used linkage-exome combinational analysis to further investigate the pedigree of a four-generation Chinese family with autosomal dominant coralliform cataract. METHODS: We combined whole exome sequencing and linkage analysis to identify the causative mutation. The exome capture and next-generation sequencing were used to sequence the protein-coding regions in the genome of the proband to identify rare mutations, which were further screened for candidate mutations in linkage regions. Candidate mutations were independently verified for co-segregation in the whole pedigree using Sanger sequencing. RESULTS: We identified a C to A transversion at nucleotide position c.70 in exon 2 of CRYGD, a cataract-associated gene. This mutation resulted in a threonine substitution for proline at amino acid residue 24. CONCLUSIONS: We identified a missense P24T mutation in CRYGD that was responsible for coralliform cataract in our studied family. Our findings suggest that the combination of exome sequencing and linkage analysis is a powerful tool for identifying Mendelian disease mutations that might be missed by the classic linkage analysis strategy.
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Pueblo Asiatico/genética , Catarata/genética , gamma-Cristalinas/genética , Catarata/congénito , Catarata/patología , China , Exones , Ligamiento Genético , Haplotipos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mutación Missense , Linaje , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Abnormal expressions of the N-methyl-D-aspartate receptor and its interacting postsynaptic density (PSD) molecules have been hypothesized to be involved in the pathophysiology of schizophrenia. Few studies have carried out association studies with DLG4 gene (coding PSD-95 protein) and sought to validate the results with Asian schizophrenia patients. PATIENTS AND METHODS: To further investigate the significance of DLG4 in Asian schizophrenic patients, we examined seven single-nucleotide polymorphisms (SNPs) within this gene in 1504 unrelated Chinese mainland individuals (893 patients and 611 controls). RESULTS: No association was found between these seven SNPs and schizophrenia within our sample. No significant differences in allele or genotype frequencies between schizophrenic paranoid patients and controls were found. CONCLUSION: Although no allelic or genotypic variances of this gene were observed, the possibility that SNPs within DLG4 represent a positive schizophrenia risk gene cannot be excluded. Our research provided a reference for further research into this gene in other populations.
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Pueblo Asiatico/genética , Etnicidad/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple/genética , Esquizofrenia/genética , Adulto , Alelos , Homólogo 4 de la Proteína Discs Large , Femenino , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Although a number of proteins and genes relevant to schizophrenia have been identified in recent years, few are known about the exact metabolic pathway involved in this disease. Our previous proteomic study has revealed the energy metabolism abnormality in subchronic MK-801 treated rat, a well-established animal model for schizophrenia. This prompted us to further investigate metabolite levels in the same rat model to better delineate the metabolism dysfunctions and provide insights into the pathology of schizophrenia. METHODS: Metabolomics, a high-throughput investigatory strategy developed in recent years, can offer comprehensive metabolite-level insights that complement protein and genetic findings. In this study, we employed a nondestructive metabolomic approach (1H-MAS-NMR) to investigate the metabolic traits in cortex and hippocampus of MK-801 treated rats. Multivariate statistics and ingenuity pathways analyses (IPA) were applied in data processing. The result was further integrated with our previous proteomic findings by IPA analysis to obtain a systematic view on our observations. RESULTS: Clear distinctions between the MK-801 treated group and the control group in both cortex and hippocampus were found by OPLS-DA models (with R(2)Xâ=â0.441, Q(2)Yâ=â0.413 and R(2)Xâ=â0.698, Q(2)Yâ=â0.677, respectively). The change of a series of metabolites accounted for the separation, such as glutamate, glutamine, citrate and succinate. Most of these metabolites fell in a pathway characterized by down-regulated glutamate synthesis and disturbed Krebs cycle. IPA analysis further confirmed the involvement of energy metabolism abnormality induced by MK-801 treatment. CONCLUSIONS: Our metabolomics findings reveal systematic changes in pathways of glutamate metabolism and Krebs cycle in the MK-801 treated rats' cortex and hippocampus, which confirmed and improved our previous proteomic observation and served as a valuable reference to the etiology research of schizophrenia.
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Maleato de Dizocilpina/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Metabolómica , Animales , Metabolismo Energético/efectos de los fármacos , Ácido Glutámico/metabolismo , Homeostasis/efectos de los fármacos , Masculino , Red Nerviosa/efectos de los fármacos , Red Nerviosa/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Factores de TiempoRESUMEN
One of the main instigators leading to cell death and brain damage following ischemia is Ca(2+) dysregulation. Neuronal membrane depolarization results in the activation of voltage-gated Ca(2+) (CaV) channels and intracellular Ca(2+) influx. We investigated the physiological role of the CaV2.1 (P/Q-type) channel in ischemic neuronal injury using CaV2.1 channel α1 subunit mutant mice, rolling Nagoya and leaner mice. The in vivo ischemia model with a complete occlusion of the middle cerebral artery showed that the infarct area at 24h was significantly smaller in rolling Nagoya (27.1±3.5% of total brain volume) and leaner (20.1±3.5%) mice compared to wild-type (42.9±4.5%) mice. In an in vitro Ca(2+) imaging study, oxygen-glucose deprivation using a hippocampal slice induced a significantly slower rate of increase in intracellular Ca(2+) concentration ([Ca(2+)]i) in rolling Nagoya (0.083±0.007/min) and leaner (0.062±0.006/min) mice compared to wild-type (0.105±0.008/min) mice. These results demonstrate that the mutant CaV2.1 channel in rolling Nagoya and leaner mice plays a different protective role in a ([Ca(2+)]i)-dependent manner in ischemic models and indicate that CaV2.1 channel blockers may be used preventively against ischemic injury.
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Isquemia Encefálica/patología , Isquemia Encefálica/fisiopatología , Canales de Calcio Tipo N/genética , Animales , Isquemia Encefálica/genética , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo N/fisiología , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Neuronas/efectos de los fármacos , Neuronas/patología , Subunidades de Proteína/genética , Subunidades de Proteína/fisiologíaRESUMEN
Schizophrenia is a complex mental disease caused by a combination of serial alterations in genetic and environmental factors. Although the brain is usually considered as the most relevant organ in schizophrenia, accumulated evidence suggests that peripheral tissues also contribute to this disease. In particular, abnormalities of the immune system have been identified in the peripheral blood of schizophrenia patients. To screen the serum proteomic signature of schizophrenia patients, we conducted shotgun proteomic analysis on serum samples of schizophrenia patients and healthy controls. High-abundance proteins were eliminated by immunoaffinity before LC-MS/MS analysis. The multivariate statistical test partial least squares-discriminant analysis (PLS-DA) was applied to build models for screening out variable importance in the projection (VIP) and 27 proteins were identified as being responsible for discriminating between the proteomic profiles of schizophrenia patients and healthy controls. Pathway analysis based on these 27 proteins revealed that complement and coagulation cascades was the most significant pathway. ELISA-based activity analyses indicated that the alternative complement pathway was suppressed in schizophrenia patients. Ingenuity pathways analysis was used to conduct the interaction network of 27 proteins. The network exhibited common features such as, nervous system development and function, humoral immune response and inflammatory response, and highlighted some proteins with important roles in the immune system, such as hub nodes. Our findings indicate dysregulation of the alternative complement pathway in schizophrenia patients. The protein interaction network enhances the interpretation of proteomic data and provides evidence that the immune system may contribute to schizophrenia.
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Vía Alternativa del Complemento , Proteínas del Sistema Complemento/inmunología , Proteómica/métodos , Esquizofrenia/inmunología , Adulto , Antipsicóticos/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/inmunología , Encéfalo/metabolismo , Estudios de Casos y Controles , Cromatografía Liquida , Vía Alternativa del Complemento/efectos de los fármacos , Proteínas del Sistema Complemento/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunidad Innata , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Mapeo de Interacción de Proteínas , Proteómica/estadística & datos numéricos , Esquizofrenia/sangre , Esquizofrenia/tratamiento farmacológico , Espectrometría de Masas en TándemRESUMEN
In this study, through linkage analysis of a four-generation Chinese family with multiple members afflicted with DGI (type II), we identified a novel missense mutation in DSPP. The mutation was located in exon 2 at the second nucleotide position of the last codon and resulted in a substitution of a proline with a leucine residue (c.50C>T, p.P17L, g.50C>T). To assess the potential effects of this novel mutation, we utilized various bioinformatics analysis programs. The results indicate that the mutation likely affects protein cleavage/trafficking. We also analyzed previously reported mutations of DSPP. In summary, our finding supports that the genomic sequence that corresponds to the P17 residue of DSPP is a mutational hotspot and P17 may be critical for the function of DSPP.
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Biología Computacional/métodos , Dentinogénesis Imperfecta/genética , Proteínas de la Matriz Extracelular/genética , Mutación Missense , Fosfoproteínas/genética , Sialoglicoproteínas/genética , Pueblo Asiatico/genética , China , Cromosomas Humanos/genética , Exones , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Ligamiento Genético , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Linaje , Fosfoproteínas/metabolismo , Análisis de Secuencia de ADN/métodos , Sialoglicoproteínas/metabolismoRESUMEN
There is considerable evidence to suggest that aberrations of synapse connectivity contribute to the pathophysiology of schizophrenia and that N-methyl-D-aspartate (NMDA) receptor-mediated glutamate transmission is especially important. Administration of MK-801 ([+]-5-methyl-10, 11-dihydro-5H-dibenzo-[a, d]-cycloheptene-5, 10-iminehydrogenmaleate) induces hypofunction of NMDA receptors in rats, which are widely used as a model for schizophrenia. We investigated synaptosomal proteome expression profiling of the cerebral cortex of MK-801-treated Sprague-Dawley rats using the 2-dimensional difference gel electrophoresis method, and 49 differentially expression proteins were successfully identified using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight/Time-of-Flight mass spectrometry. We carried out a literature search for further confirmation of subsynaptic locations and to explore the relevance to the diseases of differentially expressed proteins. Ingenuity Pathways Analysis (IPA) was used to further examine the underlying relationship between the changed proteins. The network encompassing "cell morphology, cell-to-cell signaling and interaction, nervous system development and function" was found to be significantly altered in the MK-801-treated rats. "Energy metabolism" and "semaphorin signaling in neurons" are the most significant IPA canonical pathways to be affected by MK-801 treatment. Using western blots, we confirmed the differential expression of Camk2a, Crmp2, Crmp5, Dnm1, and Ndufs3 in both synaptosome proteins and total proteins in the cerebral cortex of the rats. Our study identified the change and/or response of the central nervous transmission system under the stress of NMDA hypofunction, underlining the importance of the synaptic function in schizophrenia.
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Maleato de Dizocilpina/toxicidad , Metabolismo Energético/efectos de los fármacos , Proteoma/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Semaforinas/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Sinapsis/efectos de los fármacos , Animales , Metabolismo Energético/fisiología , Proteoma/metabolismo , Proteoma/fisiología , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/fisiología , Semaforinas/metabolismo , Semaforinas/fisiología , Transducción de Señal/fisiología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Sinapsis/patología , Sinapsis/fisiologíaRESUMEN
PURPOSE: To identify the gene mutation underlying Avellino corneal dystrophy in a four-generation Chinese pedigree. METHODS: Patients from the affected family underwent detailed clinical examination involving slit-lamp photography and confocal microscopy. Genomic DNA extracted from peripheral leukocytes was amplified using touch-down PCR for gene scanning. Two-point linkage analysis and haplotyping were performed to map the relevant chromosome region. The candidate gene in this region was sequenced to screen out the disease-causing mutation. RESULTS: Patients in the pedigree were diagnosed with Avellino corneal dystrophy. Using linkage analysis, the responsible gene was mapped to chromosome 5q31.2 with a maximum LOD (log odds) score (Z(max)) of 3.23 at D5S479 (θ(max)=0.0). Haplotypes constructed from 11 microstallite markers identified the disease-linked chromosome region as being below D5S808. Sequencing of TGFBI (transforming growth factor-beta induced gene), a known gene in this region, revealed a heterozygous transition (c.418 G>A) in exon 4 resulting in Arg124His (R124H) being co-segregated with the disease in affected family members but not in the unaffected members or the 50 unrelated controls. CONCLUSIONS: Our study demonstrated that a G>A transition in Arg124His of TGFBI was responsible for Avellino corneal dystrophy in a Chinese pedigree. This result further supports the importance of TGFBIp in maintaining transparency of the cornea.
Asunto(s)
Pueblo Asiatico/genética , Cromosomas Humanos Par 5/genética , Córnea/metabolismo , Distrofias Hereditarias de la Córnea/genética , Proteínas de la Matriz Extracelular/genética , Mutación Puntual , Factor de Crecimiento Transformador beta/genética , Adulto , Secuencia de Bases , Estudios de Casos y Controles , Córnea/patología , Distrofias Hereditarias de la Córnea/metabolismo , Análisis Mutacional de ADN , Exones , Femenino , Ligamiento Genético , Haplotipos , Heterocigoto , Humanos , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Reacción en Cadena de la PolimerasaRESUMEN
Brachydactyly type A1 (BDA1), the first recorded Mendelian autosomal dominant disorder in humans, is characterized by a shortening or absence of the middle phalanges. Heterozygous missense mutations in the Indian Hedgehog (IHH) gene have been identified as a cause of BDA1; however, the biochemical consequences of these mutations are unclear. In this paper, we analyzed three BDA1 mutations (E95K, D100E, and E131K) in the N-terminal fragment of Indian Hedgehog (IhhN). Structural analysis showed that the E95K mutation changes a negatively charged area to a positively charged area in a calcium-binding groove, and that the D100E mutation changes the local tertiary structure. Furthermore, we showed that the E95K and D100E mutations led to a temperature-sensitive and calcium-dependent instability of IhhN, which might contribute to an enhanced intracellular degradation of the mutant proteins via the lysosome. Notably, all three mutations affected Hh binding to the receptor Patched1 (PTC1), reducing its capacity to induce cellular differentiation. We propose that these are common features of the mutations that cause BDA1, affecting the Hh tertiary structure, intracellular fate, binding to the receptor/partners, and binding to extracellular components. The combination of these features alters signaling capacity and range, but the impact is likely to be variable and mutation-dependent. The potential variation in the signaling range is characterized by an enhanced interaction with heparan sulfate for IHH with the E95K mutation, but not the E131K mutation. Taken together, our results suggest that these IHH mutations affect Hh signaling at multiple levels, causing abnormal bone development and abnormal digit formation.
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Braquidactilia/genética , Proteínas Hedgehog/genética , Transducción de Señal , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Braquidactilia/metabolismo , Calcio/metabolismo , Cristalografía por Rayos X , Proteínas Hedgehog/química , Proteínas Hedgehog/metabolismo , Heparina/química , Heparina/metabolismo , Heterocigoto , Humanos , Datos de Secuencia Molecular , Mutación Missense , Receptores Patched , Receptor Patched-1 , Unión Proteica , Estructura Terciaria de Proteína , Receptores de Superficie Celular/metabolismo , TemperaturaRESUMEN
Schizophrenia is a common severe mental illness affecting 0.3-2.0% of the world's population. The potassium channels are thought to have a role in modulating electrical excitability in neurons, regulating calcium signaling in oligodendrocytes and regulating action potential duration in presynaptic terminals and GABA release. Previous studies have reported that some potassium channel genes might be candidate genes for susceptibility to schizophrenia. In the present study, we chose three potassium channel genes, KCNH1, KCNJ10, KCNN3 to investigate the role of potassium channels in schizophrenia by genotyping 23 SNPs (9 in KCNH1, 5 in KCNJ10 and 9 in KCNN3) in a Han Chinese sample consisting of 893 schizophrenia patients and 611 healthy controls. No significant difference in allelic or genotypic frequency was revealed between schizophrenia patients and healthy individuals. Nor was a significant difference in haplotypic distribution detected. MDR analysis revealed no gene-gene interaction within the three potassium channel genes. Our study suggests that the 23 SNPs within the three potassium genes we examined do not play a major role in schizophrenia in the Han Chinese population.
Asunto(s)
Canales de Potasio Éter-A-Go-Go/genética , Predisposición Genética a la Enfermedad , Canales de Potasio de Rectificación Interna/genética , Esquizofrenia/genética , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/genética , Pueblo Asiatico/etnología , Pueblo Asiatico/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Vitamin A regulates the development and maintenance of the central nervous system. Studies of vitamin A depletion (VAD) and mutations of retinoid receptors in rodents have revealed a dysfunction of motor and cognitive abilities. However, the molecular mechanisms underlying these behavioral changes are not well understood. In this study, VAD mice were examined and abnormal motor behavior related to psychosis symptoms was found. With the use of two-dimensional gel electrophoresis (2-DE), two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and mass spectrometric (MS) technologies, 44 and 23 altered protein spots were identified in the cortex and hippocampus, respectively, in VAD mice. By Western blot, the up-regulation of mitogen-activated protein kinase 1 (MAPK1) and proteasome subunit beta type 2 (PSMB2) in the cortex and that of dihydropyrimidinase-related protein 2 (DPYSL2) and PSMB2 in the hippocampus were observed in VAD mice. Bioinformatic analysis using DAVID revealed that altered proteins induced by VAD showed significant enrichment of (i) glycolysis, cytoskeleton, mitochondrion and glutamate metabolism in the cortex; and (ii) actin binding, dopamine receptor signaling and transmission of nerve impulse in the hippocampus. The up-regulations of DPYSL2, MAPK1 and PSMB2 may indicate the activated neuronal defensive mechanism in VAD brain regions, which may underlie the VAD-related psychosis behavior.
Asunto(s)
Corteza Cerebral/metabolismo , Hipocampo/metabolismo , Proteoma/metabolismo , Deficiencia de Vitamina A/metabolismo , Actinas/metabolismo , Animales , Maleato de Dizocilpina , Electroforesis en Gel Bidimensional , Femenino , Ácido Glutámico/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Espectrometría de Masas , Ratones , Ratones Endogámicos C57BL , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Psicosis Inducidas por Sustancias/metabolismo , Trastornos Psicóticos/metabolismo , Receptores Dopaminérgicos/fisiología , Transducción de Señal , Electroforesis Bidimensional Diferencial en GelRESUMEN
In this study, two polymorphisms of follicle stimulating hormone receptor (FSHR) gene were analysed in the case-control sample using 40 premature ovarian failure (POF) patients, 60 polycystic ovary syndrome (PCOS) patients and 92 healthy controls. All subjects were unrelated Han Chinese from Shanghai. No difference was observed on the allelic or genotypic distribution of FSHR gene polymorphisms between the groups. However, the two-marker haplotypes covering components Thr307Ala (rs6165) G and Asn680Ser (rs6166) A were observed to be significantly associated with PCOS (p=0.007, corrected p=0.042). Meanwhile, a meta-analysis including our study (altogether six POF and eight PCOS studies) showed significant association between rs6166 marker and PCOS (p<0.05). The results suggest that FSH receptor might play a role in genetic susceptibility to PCOS. However, confirmatory studies in independent samples are needed.
Asunto(s)
Variación Genética , Síndrome del Ovario Poliquístico/genética , Insuficiencia Ovárica Primaria/genética , Receptores de HFE/genética , Adulto , Alelos , Sustitución de Aminoácidos , Pueblo Asiatico/genética , Secuencia de Bases , Estudios de Casos y Controles , China , Cartilla de ADN/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Early growth response (EGR) genes are thought to have a role in the pathogenesis of schizophrenia because of their conserved DNA binding domain and biologically activity in neuronal plasticity. This zinc-finger motif could influence gene post-translational modification and expression. The multigenetic association model, using markers in genes of similar or antagonistic biological effects within a signal pathway or gene family, might be more appropriate to this aspect of the schizophrenia hypothesis than the single gene strategy. In this study we investigated the role of EGR1, EGR2, EGR3 and EGR4 within the EGR family. Taqman technology was used to examine 12 single nucleotide polymorphisms (SNPs) covering these four genes in 2044 Chinese Han subjects. Case-control analyses were performed to detect association of these 4 genes with schizophrenia and multifactor dimensionality reduction (MDR) analysis was employed to examine their potential gene-gene interaction in schizophrenia. Neither allelic nor genotypic single-locus tests revealed any significant association between EGR1-4 and the risk of schizophrenia nor was any such association found with regard to interaction within EGR1-4 (p(min)=0.623, CV Consistency=10/10). We concluded that although multiple candidate genes are involved in schizophrenogenic development, the EGR family may not play a major role in schizophrenia susceptibility in the Chinese Han population.
Asunto(s)
Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Esquizofrenia/genética , Transactivadores/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Regulador Transcripcional ERG , Adulto JovenRESUMEN
PURPOSE: To identify the mutant gene for autosomal dominant posterior polar congenital cataract in a four-generation Chinese pedigree. METHODS: The clinical data of patients from the family were recorded by slit-lamp photography. Genomic DNA samples from peripheral blood of the pedigree members were then isolated to map the relevant gene, using microsatellite markers for two-point linkage analysis. Genotype and haplotypes of the pedigree were constructed using Cyrillic software to locate the relevant region. Direct sequencing was performed to screen out the disease-causing mutation. RESULTS: The congenital cataract phenotype of the pedigree was labeled as the posterior polar type by using slit-lamp photography. Linkage analysis results indicated a maximum logarithm of odds LOD score of (Z(max)) 2.02 at D17S1800 (theta(max)=0.00). Haplotyping identified a 26-cM region flanked by D17S921 and D17S800 on 17p12-21.2, namely at the betaA1/A3-crystallin (CRYBA1/A3) gene locus. Sequencing revealed a splice site mutation, G-->A, at the first base of intron 3 of CRYBA1/A3, which co-segregated with the affected individuals in the pedigree but which was not found in the unaffected members of the family or in the 50 unrelated controls. CONCLUSIONS: Our results demonstrated that a splice site mutation of CRYBA1/A3 was responsible for the autosomal dominant posterior polar congenital cataract in a four-generation Chinese pedigree. The same mutation in this gene had previously been reported to be associated with other phenotype cataracts. This study is the first report relating a mutation of CRYBA1/A3 to posterior polar cataract.