title: The spreading of X inactivation into autosomal material of an x;autosome translocation: evidence for a difference between autosomal and X-chromosomal DNA.
abstract: X inactivation involves initiation, propagation, and maintenance of genetic inactivation. Studies of replication timing in X;autosome translocations have suggested that X inactivation may spread into adjacent autosomal DNA. To examine the inactivation of autosomal material at the molecular level, we assessed the transcriptional activity of X-linked and autosomal loci spanning an inactive translocation in a phenotypically normal female with a karyotype of 46,X,der(X)t(X;4)(q22;q24). Since 4q duplications usually manifest dysmorphic features and severe growth and mental retardation, the normal phenotype of this individual suggested the spreading of X inactivation throughout the autosomal material. Consistent with this model, reverse transcription-PCR analysis of 20 transcribed sequences spanning 4q24-qter revealed that three known genes and 11 expressed sequence tags (ESTs) were not expressed in a somatic-cell hybrid that carries the translocation chromosome. However, three ESTs and three known genes were expressed from the t(X;4) chromosome and thus "escaped" X inactivation. This direct assay of expression demonstrated that the spreading of inactivation from the adjoining X chromosome was incomplete and noncontiguous. These findings are broadly consistent with the existence of genes known to escape inactivation on normal inactive X chromosomes. However, the fact that a high proportion (30%) of tested autosomal genes escaped inactivation may indicate that autosomal material lacks X chromosome-specific features that are associated with the spreading and/or maintenance of inactivation.
authors.affiliation: Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: White
authors.forename: H F
authors.initials: HF
authors.lastname: Willard
authors.forename: D L
authors.initials: DL
authors.lastname: Van Dyke
authors.forename: D J
authors.initials: DJ
authors.lastname: Wolff
mesh_terms: D000328:Adult; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism; D007621:Karyotyping; D018895:Microsatellite Repeats / Q000235:genetics; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D012313:RNA; D004247:DNA