title: Nonrandom X inactivation and selection of fragile X full mutation in fetal fibroblasts.
abstract: In the fragile X female carriers the degree of cognitive impairment appears to be correlated with activation status of the X chromosome bearing the expanded trinucleotide repeat in the promoter of the FMR1 gene. In this study we asked if the deviations from the primarily random pattern of X inactivation are related to the selection which is thought to occur against cells carrying the fragile X full mutation (FM) on the active X chromosome. A fibroblast culture derived from a 20-week FM female fetus was serially passaged. The activation ratio (AR) of the culture increased from 0.68 to 0.92 between passages 2 and 9. All higher passage cells (up to 34 passages) display an AR of 1.0, indicating complete absence of cells in which the normal X chromosome would be inactivated. Of 29 clones established from the fetal culture with AR of 0.8, 28 had no visible 5.2-kb band on Southern blots indicating that these 28 clones consisted entirely of cells with FM on their inactive X chromosome. Only a single clone carried the FM on its active X chromosome. The figure of 1 of 29 is much lower than our expectation based on the AR of mass culture. Therefore cloning and serial cultivation indicate the possibility of selection depending on the activation status of the expanded X chromosome in fetal FM female fibroblasts.
authors.affiliation: Division of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, California 91010, USA. ysun@coh.org
authors.forename: Y J
authors.initials: YJ
authors.lastname: Sun
authors.forename: A
authors.initials: A
authors.lastname: Baumer
mesh_terms: D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000196:embryology / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012641:Selection, Genetic; D014960:X Chromosome / Q000235:genetics
chemical_list: D004247:DNA