THE SPREADING OF X-INACTIVATION INTO AUTOSOMAL MATERIAL OF AN X-AUTOSOME TRANSLOCATION - EVIDENCE FOR A DIFFERENCE BETWEEN AUTOSOMAL AND X-CHROMOSOMAL DNA

X inactivation involves initiation, propagation, and maintenance of ge netic inactivation. Studies of replication timing in X;autosome transl ocations have suggested that X inactivation may spread into adjacent a utosomal 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 phenotypic ally normal female with a karyotype of 46,X,der(X)t(X;4)(q22;q24). Sin ce 4q duplications usually manifest dysmorphic features and severe gro wth and mental retardation, the normal phenotype of this individual su ggested the spreading of X inactivation throughout the autosomal mater ial. 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 s omatic-cell hybrid that carries the translocation chromosome. However, three ESTs and three known genes were expressed from the t(X;4) chrom osome and thus ''escaped'' X inactivation. This direct assay of expres sion demonstrated that the spreading of inactivation from the adjoinin g X chromosome was incomplete and noncontiguous. These findings are br oadly consistent with the existence of genes known to escape inactivat ion on normal inactive X chromosomes. However, the fact that a high pr oportion (30%) of tested autosomal genes escaped inactivation may indi cate that autosomal material lacks X chromosome-specific features that are associated with the spreading and/or maintenance of inactivation.