Journal article
Re-Examination of Factors Associated with Expansion of CGG Repeats Using a Single Nucleotide Polymorphism in FMR1
Human molecular genetics, Vol.7(12), pp.1935-1946
11/01/1998
DOI: 10.1093/hmg/7.12.1935
PMID: 9811938
Abstract
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.
Details
- Title: Subtitle
- Re-Examination of Factors Associated with Expansion of CGG Repeats Using a Single Nucleotide Polymorphism in FMR1
- Creators
- Chris Gunter - Emory UniversityWilliam Paradee - Emory UniversityDana C. Crawford - Emory UniversityKellen A. Meadows - Emory UniversityJames Newman - Emory UniversityCatherine B. Kunst - Emory UniversityDavid L. Nelson - Baylor College of MedicineCharles Schwartz - Greenwood Genetic CenterAnna Murray - Salisbury District HospitalJames N. Macpherson - Salisbury District HospitalStephanie L. Sherman - Emory UniversityStephen T. Warren - Emory University
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.7(12), pp.1935-1946
- Publisher
- Oxford University Press
- DOI
- 10.1093/hmg/7.12.1935
- PMID
- 9811938
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Language
- English
- Date published
- 11/01/1998
- Academic Unit
- Medicine Administration
- Record Identifier
- 9984622760102771
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