Linked Life Data

9811938

Source:http://linkedlifedata.com/resource/pubmed/id/9811938

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1998-12-15
pubmed:databankReference
pubmed:abstractText
In at least 98% of fragile X syndrome cases, the disease results from expansion of the CGG repeat in the 5' end of FMR1. The use of microsatellite markers in the FMR1 region has revealed a disparity of risk between haplotypes for CGG repeat expansion. Although instability appears to depend on both the haplotype and the AGG interspersion pattern of the repeat, these factors alone do not completely describe the molecular basis for the linkage disequilibrium between normal and fragile X chromosomes, in part due to instability of the marker loci themselves. In an effort to better understand the mechanism of dynamic mutagenesis, we have searched for and discovered a single nucleotide polymorphism in intron 1 of FMR1 and characterized this marker, called ATL1, in 564 normal and 152 fragile X chromosomes. The G allele of this marker is found in 40% of normal chromosomes, in contrast to 83% of fragile X chromosomes. Not only is the G allele exclusively linked to haplotypes over-represented in fragile X syndrome, but G allele chromosomes also appear to transition to instability at a higher rate on haplotypes negatively associated with risk of expansion. The two alleles of ATL1 also reveal a highly significant linkage disequilibrium between unstable chromosomes and the 5' end of the CGG repeat itself, specifically the position of the first AGG interruption. The data expand the number of haplotypes associated with FMR1 and specifically allow discrimination, by ATL1 alleles, of single haplotypes with differing predispositions to expansion. Such haplotypes should prove useful in further defining the mechanism of dynamic mutagenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1935-46
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9811938-Adenine Nucleotides, pubmed-meshheading:9811938-Alleles, pubmed-meshheading:9811938-Animals, pubmed-meshheading:9811938-Fragile X Mental Retardation Protein, pubmed-meshheading:9811938-Fragile X Syndrome, pubmed-meshheading:9811938-Gene Frequency, pubmed-meshheading:9811938-Genetic Markers, pubmed-meshheading:9811938-Guanine Nucleotides, pubmed-meshheading:9811938-Haplotypes, pubmed-meshheading:9811938-Humans, pubmed-meshheading:9811938-Introns, pubmed-meshheading:9811938-Linkage Disequilibrium, pubmed-meshheading:9811938-Male, pubmed-meshheading:9811938-Microsatellite Repeats, pubmed-meshheading:9811938-Nerve Tissue Proteins, pubmed-meshheading:9811938-Pan troglodytes, pubmed-meshheading:9811938-Polymorphism, Genetic, pubmed-meshheading:9811938-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:9811938-RNA-Binding Proteins, pubmed-meshheading:9811938-Trinucleotide Repeats
pubmed:year
1998
pubmed:articleTitle
Re-examination of factors associated with expansion of CGG repeats using a single nucleotide polymorphism in FMR1.
pubmed:affiliation
Departments of Biochemistry, Pediatrics and Genetics, Emory University School of Medicine and Howard Hughes Medical Institute, Emory University, Atlanta, GA 30322, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.