Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
PLoS Genet ; 8(6): e1002753, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22685421

RESUMO

As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, ß = -0.16 mm per minor allele, P(meta) =2.69 × 10(-10)). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) =0.75, 95% CI: 0.68-0.84, P(meta) =4.38 × 10(-7)) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.


Assuntos
Proteínas de Transporte/genética , Cromossomos Humanos Par 1/genética , Estudo de Associação Genômica Ampla , Miopia/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Animais , Proteínas de Transporte de Cátions/genética , Criança , China , Modelos Animais de Doenças , Feminino , Expressão Gênica , Predisposição Genética para Doença , Humanos , Lisofosfolipase/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas Nucleares , Proteínas de Ligação a RNA , Retina/metabolismo , Retina/patologia , Epitélio Pigmentado da Retina/metabolismo , Esclera/metabolismo , Esclera/patologia , Transportador 8 de Zinco
2.
Mol Vis ; 18: 1436-48, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22736935

RESUMO

PURPOSE: The aim of this study was to identify the genes and pathways underlying the growth of the mouse sclera during postnatal development. METHODS: Total RNA was isolated from each of 30 single mouse sclera (n=30, 6 sclera each from 1-, 2-, 3-, 6-, and 8-week-old mice) and reverse-transcribed into cDNA using a T7-N(6) primer. The resulting cDNA was fragmented, labeled with biotin, and hybridized to a Mouse Gene 1.0 ST Array. ANOVA analysis was then performed using Partek Genomic Suite 6.5 beta and differentially expressed transcript clusters were filtered based on a selection criterion of ≥ 2 relative fold change at a false discovery rate of ≤ 5%. Genes identified as involved in the main biologic processes during postnatal scleral development were further confirmed using qPCR. A possible pathway that contributes to the postnatal development of the sclera was investigated using Ingenuity Pathway Analysis software. RESULTS: The hierarchical clustering of all time points showed that they did not cluster according to age. The highest number of differentially expressed transcript clusters was found when week 1 and week 2 old scleral tissues were compared. The peroxisome proliferator- activated receptor gamma coactivator 1-alpha (Ppargc1a) gene was found to be involved in the networks generated using Ingenuity Pathway Studio (IPA) from the differentially expressed transcript cluster lists of week 2 versus 1, week 3 versus 2, week 6 versus 3, and week 8 versus 6. The gene expression of Ppargc1a varied during scleral growth from week 1 to 2, week 2 to 3, week 3 to 6, and week 6 to 8 and was found to interact with a different set of genes at different scleral growth stages. Therefore, this indicated that Ppargc1a might play a role in scleral growth during postnatal weeks 1 to 8. CONCLUSIONS: Gene expression of eye diseases should be studied as early as postnatal weeks 1-2 to ensure that any changes in gene expression pattern during disease development are detected. In addition, we propose that Ppargc1a might play a role in regulating postnatal scleral development by interacting with a different set of genes at different scleral growth stages.


Assuntos
Proteínas do Olho/genética , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Genoma , Esclera/metabolismo , Transativadores/genética , Animais , Animais Recém-Nascidos , Proteínas do Olho/metabolismo , Perfilação da Expressão Gênica , Camundongos , Camundongos Endogâmicos BALB C , Família Multigênica , Análise de Sequência com Séries de Oligonucleotídeos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , RNA Mensageiro , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esclera/crescimento & desenvolvimento , Software , Fatores de Tempo , Transativadores/metabolismo , Fatores de Transcrição
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA