Assuntos
Mutação , Proteínas/genética , Retroelementos , Alelos , Animais , Sequência de Bases , Primers do DNA/genética , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo Genético , Splicing de RNA , Proteínas de Transporte VesicularRESUMO
The beige mutation is a murine autosomal recessive disorder, resulting in hypopigmentation, bleeding and immune cell dysfunction. The gene defective in beige is thought to be a homologue of the gene for the human disorder Chediak-Higashi syndrome. We have identified the murine beige gene by in vitro complementation and positional cloning, and confirmed its identification by defining mutations in two independent mutant alleles. The sequence of the beige gene message shows strong nucleotide homology to multiple human ESTs, one or more of which may be associated with the Chediak-Higashi syndrome gene. The amino acid sequence of the Beige protein revealed a novel protein with significant amino acid homology to orphan proteins identified in Saccharomyces cerevisiae, Caenorhabditis elegans and humans.
Assuntos
Síndrome de Chediak-Higashi/genética , Mutação , Proteínas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Artificiais de Levedura , Clonagem Molecular/métodos , Teste de Complementação Genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Camundongos Endogâmicos , Camundongos Mutantes , Dados de Sequência Molecular , Biossíntese de Proteínas , Proteínas/química , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Proteínas de Transporte VesicularRESUMO
Chédiak-Higashi syndrome in man and the beige mutation of mice are phenotypically similar disorders that have profound effects upon lysosome and melanosome morphology and function. We isolated two murine yeast artificial chromosomes (YACs) that, when introduced into beige mouse fibroblasts, complement the beige mutation. The complementing YACs exist as extrachromosomal elements that are amplified in high concentrations of G418. When YAC-complemented beige cells were fused to human Chédiak-Higashi syndrome or Aleutian mink fibroblasts, complementation of the mutant phenotype also occurred. These results localize the beige gene to a 500-kb interval and demonstrate that the same or homologous genes are defective in mice, minks, and humans.
Assuntos
Cromossomos Artificiais de Levedura , Teste de Complementação Genética , Mutação , Plasmídeos , Animais , Células Cultivadas , Síndrome de Chediak-Higashi/genética , Fibroblastos , Vetores Genéticos , Humanos , Camundongos , Vison , Pigmentação/genética , Especificidade da EspécieRESUMO
PIP: The relationships between migration trends and changes in socioeconomic structures, settlement systems, and regional development programs in developing countries are analyzed. Current and possible future trends in urbanization in Southeast Asia are summarized, with a focus on the effects of migration. The impact of internal migration on spatial distibution in Thailand, Malaysia, Indonesia, and the Philippines is examined. The need for taking cultural traditions into consideration in the formulation of population policies and programs is emphasized.^ieng
