Linked Life Data

14526174

Source:http://linkedlifedata.com/resource/pubmed/id/14526174

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-4
pubmed:dateCreated
2003-10-3
pubmed:abstractText
Repeat expansion diseases such as fragile X syndrome (FXS) result from increases in the size of a specific tandem repeat array. In addition to large expansions, small changes in repeat number and deletions are frequently seen in FXS pedigrees. No mouse model accurately recapitulates all aspects of this instability, particularly the occurrence of large expansions. This may be due to differences between mice and humans in CIS and/or TRANS-acting factors that affect repeat stability. The identification of such factors may help reveal the expansion mechanism and allow the development of suitable animal models for these disorders. We have examined the effect of age, dietary folate, and mutations in the Werner's syndrome helicase (WRN) and TRP53 genes on FXS repeat instability in mice. WRN facilitates replication of the FXS repeat and enhances Okazaki fragment processing, thereby reducing the incidence of processes that have been suggested to lead to expansion. p53 is a protein involved in DNA damage surveillance and repair. We find two types of repeat instability in these mice, small changes in repeat number that are seen at frequencies approaching 100%, and large deletions which occur at a frequency of about 10%. The frequency of these events was independent of WRN, p53, parental age, or folate levels. The large deletions occur at the same frequency in mice homozygous and heterozygous for the repeat suggesting that they are not the result of an interallelic recombination event. In addition, no evidence of large expansions was seen. Our data thus show that the absence of repeat expansions in mice is not due to a more efficient WRN protein or p53-mediated error correction mechanism, and suggest that these proteins, or the pathways in which they are active, may not be involved in expansion in humans either. Moreover, the fact that contractions occur in the absence of expansions suggests that these processes occur by different mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1424-859X
pubmed:author
pubmed:copyrightInfo
Copyright 2003 S. Karger AG, Basel
pubmed:issnType
Electronic
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
140-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14526174-Age Factors, pubmed-meshheading:14526174-Animals, pubmed-meshheading:14526174-Crosses, Genetic, pubmed-meshheading:14526174-DNA, pubmed-meshheading:14526174-DNA Helicases, pubmed-meshheading:14526174-DNA Repair, pubmed-meshheading:14526174-DNA Replication, pubmed-meshheading:14526174-Deoxyribonucleases, Type II Site-Specific, pubmed-meshheading:14526174-Female, pubmed-meshheading:14526174-Folic Acid, pubmed-meshheading:14526174-Fragile X Syndrome, pubmed-meshheading:14526174-Genotype, pubmed-meshheading:14526174-Male, pubmed-meshheading:14526174-Mice, pubmed-meshheading:14526174-Mice, Inbred Strains, pubmed-meshheading:14526174-Mice, Knockout, pubmed-meshheading:14526174-Mutation, pubmed-meshheading:14526174-Recombination, Genetic, pubmed-meshheading:14526174-Sequence Deletion, pubmed-meshheading:14526174-Trinucleotide Repeat Expansion, pubmed-meshheading:14526174-Tumor Suppressor Protein p53
pubmed:year
2003
pubmed:articleTitle
Instability of the fragile X syndrome repeat in mice: the effect of age, diet and mutations in genes that affect DNA replication, recombination and repair proficiency.
pubmed:affiliation
Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA.
pubmed:publicationType
Journal Article