Linked Life Data

15241793

Source:http://linkedlifedata.com/resource/pubmed/id/15241793

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-7-8
pubmed:abstractText
Classic cystic fibrosis (CF) is caused by two loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, whereas patients with nonclassic CF have at least one copy of a mutant gene that retains partial function of the CFTR protein. In addition, there are several other phenotypes associated with CFTR gene mutations, such as idiopathic chronic pancreatitis. In CFTR-associated disorders and in nonclassic CF, often only one CFTR mutation or no CFTR mutations can be detected. In this study, we screened 23 patients with CFTR-associated disorders for CFTR mutations by complete gene testing and quantitative transcript analysis. Mutations were found in 10 patients. In cells from respiratory epithelium, we detected aberrant splicing of CFTR mRNA in all investigated individuals. We observed a highly significant association between the presence of coding single-nucleotide polymorphisms (coding SNPs, or cSNPs) and increased skipping of exon 9 and 12. This association was found both in patients and in normal individuals carrying the same cSNPs. The cSNPs c.1540A>G, c.2694T>G, and c.4521G>A may have affected pre-mRNA splicing by changing regulatory sequence motifs of exonic splice enhancers, leading to lower amounts of normal transcripts. The analysis of CFTR exons indicated that less frequent and weak exonic splicing enhancer (ESE) motifs make exon 12 vulnerable to skipping. The number of splice variants in individuals with cSNPs was similar to previously reported values for the T5 allele, suggesting that cSNPs may enhance susceptibility to CFTR related diseases. In addition, cSNPs may be responsible for variation in the phenotypic expression of CFTR mutations. Quantitative approaches rather than conventional genomic analysis are required to interpret the role of cSNPs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1098-1004
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
120-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15241793-Adolescent, pubmed-meshheading:15241793-Alleles, pubmed-meshheading:15241793-Alternative Splicing, pubmed-meshheading:15241793-Base Composition, pubmed-meshheading:15241793-Binding Sites, pubmed-meshheading:15241793-Child, Preschool, pubmed-meshheading:15241793-Codon, pubmed-meshheading:15241793-Computational Biology, pubmed-meshheading:15241793-Cystic Fibrosis Transmembrane Conductance Regulator, pubmed-meshheading:15241793-DNA Mutational Analysis, pubmed-meshheading:15241793-Enhancer Elements, Genetic, pubmed-meshheading:15241793-Exons, pubmed-meshheading:15241793-Humans, pubmed-meshheading:15241793-Male, pubmed-meshheading:15241793-Mutation, pubmed-meshheading:15241793-Nuclear Proteins, pubmed-meshheading:15241793-Polymorphism, Single Nucleotide, pubmed-meshheading:15241793-RNA, Messenger, pubmed-meshheading:15241793-RNA Splice Sites, pubmed-meshheading:15241793-Respiratory Mucosa, pubmed-meshheading:15241793-Transcription, Genetic
pubmed:year
2004
pubmed:articleTitle
The role of common single-nucleotide polymorphisms on exon 9 and exon 12 skipping in nonmutated CFTR alleles.
pubmed:affiliation
Department of Pediatrics, Division of Human Genetics, Inselspital, University of Berne, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't