RESUMEN
The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
Asunto(s)
Genoma Humano , Proyecto Genoma Humano , Análisis de Secuencia de ADN , Animales , Mapeo Cromosómico , Secuencia Conservada , Islas de CpG , Elementos Transponibles de ADN , Bases de Datos Factuales , Industria Farmacéutica , Evolución Molecular , Predicción , Secuencia Rica en GC , Duplicación de Gen , Genes , Enfermedades Genéticas Congénitas , Genética Médica , Humanos , Mutación , Sector Privado , Proteínas/genética , Proteoma , Sector Público , ARN/genética , Secuencias Repetitivas de Ácidos Nucleicos , Análisis de Secuencia de ADN/métodos , Especificidad de la EspecieRESUMEN
Homozygous staggerer (sg) mice show a characteristic severe cerebellar ataxia due to a cell-autonomous defect in the development of Purkinje cells. These cells show immature morphology, synaptic arrangement, biochemical properties and gene expression, and are reduced in numbers. In addition, sg heterozygotes show accelerated dendritic atrophy and cell loss, suggesting that sg has a role in mature Purkinje cells. Effects of this mutation on cerebellar development have been studied for 25 years, but its molecular basis has remained unknown. We have genetically mapped staggerer to an interval of 160 kilobases on mouse chromosome 9 which was found to contain the gene encoding RORalpha, a member of the nuclear hormone-receptor superfamily. Staggerer mice were found to carry a deletion within the RORalpha gene that prevents translation of the ligand-binding homology domain. We propose a model based on these results, in which RORalpha interacts with the thyroid hormone signalling pathway to induce Purkinje-cell maturation.
Asunto(s)
Proteínas de Unión al ADN/genética , Ratones Mutantes Neurológicos/genética , Receptores de Superficie Celular/genética , Receptores Citoplasmáticos y Nucleares/genética , Transactivadores/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Encéfalo/citología , Encéfalo/embriología , Encéfalo/metabolismo , Diferenciación Celular/fisiología , Ataxia Cerebelosa/genética , Mapeo Cromosómico , ADN Complementario , Proteínas de Unión al ADN/fisiología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Células de Purkinje/patología , Receptores de Superficie Celular/fisiología , Receptores Citoplasmáticos y Nucleares/fisiología , Transactivadores/fisiologíaRESUMEN
Computer-aided sequencing and analysis facilities need to efficiently search flat archive files. Retrieval by e-mail or network server connections can become impractical in cases where large numbers of selected entries need to be accessed. Public versions of these archives can be retrieved via ftp and installed on a local hard disk as an alternative to network-based retrieval. After installation, a scheme is required for rapid access of the archive that is consistent with the other production needs of the sequencing facility. We have developed a retrieval system for entries inside a flat-file database. The system works for any flat-file database system such as those used in the public DNA and protein archives.