RESUMEN
The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of the human genome sequence, with confirmed gene predictions that have been integrated with external data sources, and is available as either an interactive web site or as flat files. It is also an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements from sequence analysis to data storage and visualisation. The Ensembl site is one of the leading sources of human genome sequence annotation and provided much of the analysis for publication by the international human genome project of the draft genome. The Ensembl system is being installed around the world in both companies and academic sites on machines ranging from supercomputers to laptops.
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Bases de Datos Genéticas , Genoma Humano , Biología Computacional , Sistemas de Administración de Bases de Datos , Humanos , Almacenamiento y Recuperación de la Información , Internet , Análisis de Secuencia de ADN , Integración de SistemasRESUMEN
Recent evidence points to the involvement of vascular endothelial growth factor (VEGF) in mammalian reproductive physiology. Transgenic mice expressing VEGF (121 isoform) under the control of the polyepithelial mucin-1 (muc-1) promoter showed a reduction in male fertility due to impaired spermiogenesis, and aberrant placentation leading to preferential rejection of male embryos. A skew in the sex ratio of the litters was seen (three females to two males), independently of whether the transgene was carried by the male or female parent. In-situ hybridization permitted distinction of expression of the human VEGF transgene from endogenous mouse VEGF, and confirmed expression of the transgene in a wide range of epithelial tissues. Expression of the transgene in spermatocytes and in the embryonic portion of placenta is thought to be responsible for the reduced fertility and embryonic resorptions respectively. Males showed either complete sperm maturation arrest or various gradations of partial fertility. Abnormally high or low VEGF in human semen has been reported to be correlated with a lack of pregnancy success following IVF. The muc1-VEGF (121 isoform) transgenic mouse provides an animal model with which to further study this VEGF-induced pathology.
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Factores de Crecimiento Endotelial/fisiología , Fertilidad/fisiología , Linfocinas/fisiología , Placenta/fisiología , Animales , Factores de Crecimiento Endotelial/biosíntesis , Factores de Crecimiento Endotelial/genética , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Expresión Génica , Humanos , Hibridación in Situ/métodos , Etiquetado Corte-Fin in Situ , Riñón/embriología , Linfocinas/biosíntesis , Linfocinas/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Transgénicos , Microscopía Electrónica , Mucinas/genética , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas , Proteínas Tirosina Quinasas Receptoras , Receptores de Factores de Crecimiento , Receptores de Factores de Crecimiento Endotelial Vascular , Testículo/patología , Testículo/ultraestructura , Factor A de Crecimiento Endotelial Vascular , Receptor 1 de Factores de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
The endothelium plays a pivotal role in many physiological and pathological processes and is known to be an exceptionally active transcriptional site. To advance our understanding of endothelial cell biology and to elucidate potential pharmaceutical targets, we developed a new database screening approach to permit identification of novel endothelial-specific genes. The UniGene gene index was screened using high stringency BLAST against a pool of endothelial expressed sequence tags (ESTs) and a pool of nonendothelial ESTs constructed from cell-type-specific dbEST libraries. UniGene clusters with matches in the endothelial pool and no matches in the nonendothelial pool were selected. The UniGene/EST approach was then combined with serial analysis of gene expression (SAGE) library subtraction and reverse transcription polymerase chain reaction to further examine interesting clusters. Four novel genes were identified and labeled: endothelial cell-specific molecules (ECSM) 1-3 and magic roundabout (similar to the axon guidance protein roundabout). In summary, we present a powerful novel approach for comparative expression analysis combining two datamining strategies followed by experimental verification.
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Clonación Molecular/métodos , ADN de Neoplasias/genética , Endotelio/fisiología , Adulto , Animales , Línea Celular , Biología Computacional , Bases de Datos Factuales , Endotelio/metabolismo , Endotelio/patología , Etiquetas de Secuencia Expresada , Femenino , Expresión Génica , Biblioteca de Genes , Humanos , Masculino , Ratones , Familia de Multigenes , Programas Informáticos , Células Tumorales CultivadasAsunto(s)
Distrofia Miotónica/genética , Proteínas Serina-Treonina Quinasas , Animales , ADN Polimerasa Dirigida por ADN/metabolismo , Humanos , Meiosis , Mutación , Proteína Quinasa de Distrofia Miotónica , Fenotipo , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Aberraciones Cromosómicas Sexuales/genética , Cromosoma XRESUMEN
Ribonucleoprotein telomerase is an enzyme that elongates telomeric DNA. In cells without detectable telomerase activity telomeres shorten with every cell generation and reaching critical length is a signal for cell death. Normal human somatic cells express undetectable, or low (bone marrow and peripheral leukocytes), telomerase activity. Reactivation of telomerase (immortalization) is probably necessary during development of a fully malignant cancer. Consequently, telomerase was proposed to be a therapeutic target for the cancer therapy. Potential results (including side-effects) of telomerase inhibition are being considered. After all, telomerase inhibition can be useful not only in the therapy, but also in cancer biology research, elucidating ageing and immortalization phenomena.