Nature Genetics
8, 229 - 235 (1994)
doi:10.1038/ng1194-229
Isolation of a GCC repeat showing expansion in FRAXF, a fragile site distal to FRAXA and FRAXEJulia E. Parrish1, Ben A. Oostra2, Annemieke J.M.H. Verkerk2, C. Sue Richards1, James Reynolds3, Aimee S. Spikes1, Lisa G. Shaffer1
& David L. Nelson1, 4
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
2Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands
3Shodair Hospital, Helena, Montana 59604, USA
4Correspondence should be addressed to D.L.N. Three folate-sensitive fragile sites, termed FRAXA, FRAXE and FRAXF, have been identified on the distal end of chromosome Xq. The first two contain expanded, hypermethylated and unstable CGG (or GCC) repeats within CpG islands. We now report the isolation of similar sequences responsible for the third fragile site, FRAXF. A 5-kilobase EcoRI fragment derived from a cosmid coincident with the cytogenetic anomaly detects expanded, methylated and unstable sequences in five individuals who exhibit fragile sites in distal Xq; these individuals have normal repeat lengths at both FRAXA and FRAXE. By sequence analysis, the expanded region contains a GCC repeat. PCR and sequence analysis of chromosomes from the general population indicates that the repeat is polymorphic (6 to 29 triplets), and is stable upon transmission.
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