RESUMO
PURPOSE: To study the genetic basis of autosomal dominant posterior polar cataracts in two Chinese pedigrees. MATERIALS AND METHODS: Peripheral blood samples were collected and genomic DNA was isolated. A genome-wide scan, using microsatellite markers at approximately 10-cm intervals and additional microsatellite markers for the positive region, was performed. Haplotype data were processed using Cyrillic software (version 2.1) to define the region of the disease gene. Mutation analysis was carried out for candidate genes. Sequencing data were analyzed with the software Sequence Scanner v1.0. RESULTS: A maximum two-point LOD score (Z (max)) of 2.53 and 2.03 was obtained at marker D2S125 with recombination θ = 0.00 in the two families. The possible disease genes were located at approximately 8.44-cM between the marker D2S125 and the terminal of chromosome 2q, namely, 2q37-qter. Candidate genes, such as Gamma-crystallins (CRYGA-D), septin 2 (SEPT2), aquaporin 12B (AQP12B), and chemokine orphan receptor 7 (CXCR7), were sequenced but no causative mutations were found. CONCLUSIONS: Our results suggest that an unidentified gene in chromosome 2q37-qter is associated with posterior polar cataract, which may have an implication in understanding the genetic and molecular mechanisms of cataracts.
Assuntos
Catarata/genética , Cromossomos Humanos Par 2/genética , Loci Gênicos , Adolescente , Adulto , Idoso , Catarata/patologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Ligação Genética , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Escore Lod , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Linhagem , Adulto JovemRESUMO
Retinoic acid (Ra) is crucial for the patterning and neuronal differentiation in the central nervous system (CNS). Ra deficiency in animals disrupts the motor activities and memory abilities. The molecular mechanisms underlying these behavior abnormalities remain largely unknown. In the current study, we treated the astrocytoma cells with citral, an inhibitor of Ra synthesis. We analyzed the differences in the protein concentrations between the treated and untreated astrocytoma cells by two-dimensional gel electrophoresis (2-DE), Imagemaster software, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In total, 39 of 46 altered protein spots with significant mascot scores were identified representing 36 proteins, that were involved in significantly altered glutamate metabolism, lipid metabolism, mitochondrial function, and oxidative stress response by Ingenuity Pathway Analysis (IPA). Altered 3-phosphoglycerate dehydrogenase (PHGDH) was also observed in western blot. These data provide some clues for explaining the behavioral changes caused by Ra deficiency, and support the hypothesis that Ra signaling is associated with some symptoms of neurodegenerative disorders and schizophrenia.
Assuntos
Astrocitoma/metabolismo , Proteoma/metabolismo , Tretinoína/metabolismo , Monoterpenos Acíclicos , Animais , Linhagem Celular Tumoral/efeitos dos fármacos , Biologia Computacional/métodos , Eletroforese em Gel Bidimensional , Humanos , Dados de Sequência Molecular , Monoterpenos/farmacologia , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Desidrogenase/metabolismo , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Serotonin transmission has long been suspected as being involved in the pathogenesis of schizophrenia. 5-HTT is a promising candidate gene for schizophrenia due to its critical role in regulating serotonin transmission and role in the mechanism of the atypical antipsychotic drugs. A common polymorphism STin2 VNTR in the 5-HTT gene has been extensively investigated in the genetic association studies, but the results are conflicting. Meanwhile, the SNPs of the 5-HTT gene have been much less explored. We therefore conducted a case-control study of the association between STin2 VNTR and three tagging SNPs in 5-HTT and schizophrenia in the Han Chinese population based on a cohort of 329 schizophrenic patients and 288 control subjects. No association was found in the single locus, but haplotype-based analyses revealed significant association between two haplotypes with schizophrenia even after Bonferroni correction (P=0.00000538 and 0.011).