RESUMO
Multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH) are autosomal dominant chondrodysplasias that have similar phenotypes at both clinical and cytological levels. With the recent mapping of PSACH and one form of MED (EDM1) to the pericentromeric region of chromosome 19, it is likely that the disease mutations are allelic. D19S212 and D19S215, genetic markers flanking the EDM1/PSACH locus, have been localized in a chromosome 19 physical map consisting of cosmid contigs ordered by high-resolution FISH. These two markers define an interval of approximately 3.1 Mb at the 19p13.1-p12 boundary. With as many as five informative crossovers within the D19S212-D19S215 interval in one family with EDM1 and one family with a mild form of PSACH, recombination mapping at greater resolution was undertaken. From cosmid contigs physically mapped within the D19S212-D19S215 interval, four new dinucleotide repeat polymorphisms have been identified. Analysis of recombinant haplotypes in the two families has narrowed the possible location of the EDM1/PSACH gene to an interval of approximately 600 kb.
Assuntos
Cromossomos Humanos Par 19 , Osteocondrodisplasias/genética , Sequência de Bases , Primers do DNA , Feminino , Marcadores Genéticos , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , Mutação , Linhagem , Polimorfismo Genético , Sequências Repetitivas de Ácido Nucleico , Mapeamento por RestriçãoRESUMO
A base substitution of G to U was constructed at position 529 in Escherichia coli 16S rRNA. The U529 mutant ribosomes were functional and present on polysomes but were highly error prone and caused a progressive loss of cell viability. They displayed elevated levels of readthrough of stop codons and frameshifting, and an increase in thermal sensitivity of beta-galactosidase, suggestive of missense errors. These results demonstrate that the university conserved G529 is involved in tRNA selection at the A site during protein synthesis.
Assuntos
Escherichia coli/genética , Biossíntese de Proteínas , RNA Ribossômico 16S/genética , Ribossomos/metabolismo , Sequência de Bases , Sequência Conservada , Escherichia coli/crescimento & desenvolvimento , Temperatura Alta , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Mutação , Conformação de Ácido Nucleico , Polirribossomos/metabolismo , Desnaturação Proteica , RNA , RNA Mensageiro/metabolismo , beta-Galactosidase/biossínteseRESUMO
Expression of human GLVR1 in mouse cells confers susceptibility to infection by gibbon ape leukemia virus (GALV), while the normally expressed mouse Glvr-1 does not. Since human and murine GLVR1 proteins differ at 64 positions in their sequences, some of the residues differing between the two proteins are critical for infection. To identify these, a series of hybrids and in vitro-constructed mutants were tested for the ability to confer susceptibility to infection. The results indicated that human GLVR1 residues 550 to 551, located in a cluster of seven of the sites that differ between the human and mouse proteins, are the only residues differing between the two which must be in the human protein form to allow infection. Sequencing of a portion of GLVR1 from the rat (which is infectible) confirmed the importance of this cluster in that it contained the only notable differences between the rat and mouse proteins. This region, which also differs substantially between the rat and the human proteins, therefore exhibits a pronounced tendency for polymorphism.
