Missense Mutations in hMLH1 and hMSH2 Are Associated with Exonic Splicing Enhancers
نویسندگان
چکیده
منابع مشابه
Missense mutations of MLH1 and MSH2 genes detected in patients with gastrointestinal cancer are associated with exonic splicing enhancers and silencers
The MLH1 and MSH2 genes in DNA mismatch repair are important in the pathogenesis of gastrointestinal cancer. Recent studies of normal and alternative splicing suggest that the deleterious effects of missense mutations may in fact be splicing-related when they are located in exonic splicing enhancers (ESEs) or exonic splicing silencers (ESSs). In this study, we used ESE-finder and FAS-ESS softwa...
متن کاملPathogenicity of missense and splice site mutations in hMSH2 and hMLH1 mismatch repair genes: implications for genetic testing.
BACKGROUND In hereditary non-polyposis colorectal cancer, over 90% of the identified mutations are in two genes, hMSH2 and hMLH1. A large proportion of the mutations detected in these genes are of the missense type which may be either deleterious mutations or harmless polymorphisms. AIM To investigate whether nine missense and one splice site mutation of hMLH1 and hMSH2, in 10 kindreds with a...
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Hereditary NonPolyposis Colorectal Cancer (Lynch syndrome) is an autosomal dominant disease caused by germline mutations in a class of genes deputed to maintain genomic integrity during cell replication, mutations result in a generalized genomic instability, particularly evident at microsatellite loci (Microsatellite Instability, MSI). MSI is present in 85-90% of colorectal cancers that occur i...
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Silent sites in mammals have classically been assumed to be free from selective pressures. Consequently, the synonymous substitution rate (Ks) is often used as a proxy for the mutation rate. Although accumulating evidence demonstrates that the assumption is not valid, the mechanism by which selection acts remain unclear. Recent work has revealed that the presence of exonic splicing enhancers (E...
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A typical gene contains two levels of information: a sequence that encodes a particular protein and a host of other signals that are necessary for the correct expression of the transcript. While much attention has been focused on the effects of sequence variation on the amino acid sequence, variations that disrupt gene processing signals can dramatically impact gene function. A variation that d...
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ژورنال
عنوان ژورنال: The American Journal of Human Genetics
سال: 2003
ISSN: 0002-9297
DOI: 10.1086/378819