Vinculando La Deficiencia De C5 Al Splicing Exonico Y Como Estimulante De Mutacion
Páginas: 3 (671 palabras)
Publicado: 15 de noviembre de 2012
UNIVERSIDAD DE GUAYAQUIL
Nombre: Andrés Cuenca Orellana
Tercer año grupo 20
Cátedra: Inmunología
Linking C5 deficiency to an exonic splicing enhancer mutation.
Abstract
As an importantcomponent of the innate immune system, complement provides the initial response to prevent infections by pathogenic microorganisms. Patients with dysfunction of C5 display a propensity for severerecurrent infections. In this study, we present a patient with C5 deficiency demonstrated by immunochemical and functional analyses. Direct sequencing of all C5 exons displayed no mutation of obviousfunctional significance, except for an A to G transition in exon 10 predicting an exchange from lysine to arginine. This sequence alteration was present in only one allele of family members with a reducedserum C5 concentration and in both alleles of the patient with almost complete C5 deficiency, suggesting that this alteration may be producing the phenotype. Recent findings indicate that distinctnucleotide sequences, termed exonic splicing enhancers (ESEs), influence the splicing process. cDNA from all family members harboring the mutated allele showed skipping of exon 10, which resulted in apremature STOP codon, explaining the lack of C5 in the propositus. Sequence analysis of the mutated region revealed the substitution to be located within an ESE, as predicted by the RESCUE-ESE program.The altered ESE sequence is located close to the 5' splicing site and also lowers the predicted strength of the splice site itself. This apparently inconsequential sequence alteration represents anoncanonical splicing mutation altering an ESE. Our finding sheds a new light on the role of putative silent/conservative mutations in disease-associated genes.
¿Que hicieron los investigadores?Buscan la relación de la deficiencia del complemento C5 a una mutacion exonica en el proceso de splicing o empalme dado que la deficiencia de este produce un aumento de infección de agentes patógenos...
Nombre: Andrés Cuenca Orellana
Tercer año grupo 20
Cátedra: Inmunología
Linking C5 deficiency to an exonic splicing enhancer mutation.
Abstract
As an importantcomponent of the innate immune system, complement provides the initial response to prevent infections by pathogenic microorganisms. Patients with dysfunction of C5 display a propensity for severerecurrent infections. In this study, we present a patient with C5 deficiency demonstrated by immunochemical and functional analyses. Direct sequencing of all C5 exons displayed no mutation of obviousfunctional significance, except for an A to G transition in exon 10 predicting an exchange from lysine to arginine. This sequence alteration was present in only one allele of family members with a reducedserum C5 concentration and in both alleles of the patient with almost complete C5 deficiency, suggesting that this alteration may be producing the phenotype. Recent findings indicate that distinctnucleotide sequences, termed exonic splicing enhancers (ESEs), influence the splicing process. cDNA from all family members harboring the mutated allele showed skipping of exon 10, which resulted in apremature STOP codon, explaining the lack of C5 in the propositus. Sequence analysis of the mutated region revealed the substitution to be located within an ESE, as predicted by the RESCUE-ESE program.The altered ESE sequence is located close to the 5' splicing site and also lowers the predicted strength of the splice site itself. This apparently inconsequential sequence alteration represents anoncanonical splicing mutation altering an ESE. Our finding sheds a new light on the role of putative silent/conservative mutations in disease-associated genes.
¿Que hicieron los investigadores?Buscan la relación de la deficiencia del complemento C5 a una mutacion exonica en el proceso de splicing o empalme dado que la deficiencia de este produce un aumento de infección de agentes patógenos...
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