the role of agg interruptions in the transcription of fmr1 premutation allelesgg中断的作用的转录fmr1前突变等位基因.pdfVIP

The Role of AGG Interruptions in the Transcription of FMR1 Premutation Alleles 1 1 2 1,3 Carolyn M. Yrigollen , Federica Tassone , Blythe Durbin-Johnson , Flora Tassone * 1 Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Davis, California, United States of America, 2 Department of Public Health Sciences School of Medicine, University of California Davis, Davis, California, United States of America, 3 M.I.N.D. Institute, University of California Davis Medical Center, Davis, California, United States of America Abstract Fragile X associated disorders are caused by a premutation allele in the fragile X mental retardation 1 gene (FMR1) and are hypothesized to result from the toxic effect of elevated levels of expanded FMR1 transcripts. Increased levels of FMR1 mRNA have indeed been reported in premutation carriers; however the mechanism by which expanded alleles lead to elevated levels of FMR1 mRNA in premutation carriers is unknown. Within the CGG repeat tract AGG interruptions are found, generally 1–3 present in normal/intermediate alleles (6–54 CGG repeats) and usually 0–1 in premutation alleles (55–200 CGG repeats). They are present at specific locations, generally occurring after 9 or 10 uninterrupted CGG repeats [(CGG) AGG(CGG) AGG(CGG) ]. We evaluated both the number of AGG interruptions and the resulting length of the 9 9 n uninterrupted 39 CGG repeat pure tract in premutation alleles derived from two large cohorts of male and female carriers to determine whether the presence of AGG interruptions or the length of a pure stretch of CGG repeats