Abstract
Differential replication staining using the 5-bromo-2′-deoxyuridine+Hoechst 33258
technique has been carried out on a series of 28 girls with Rett syndrome (RTT). The
results indicated that regions Xq23 and Xq28 of inactive chromosome X could contain
early replicating and, therefore, transcriptionally active loci in RTT. Interphase
fluorescence in situ hybridization studies of replication timing, using chromosome
X-specific genomic DNA probes, was applied to determine the loci with altered replication
and transcription in RTT. Randomly selected P1 artificial chromosome (PAC) clones
for Xp, Xcen and Xq were used. Two PAC clones from Xq28 (anonymous clone 24.23.0 and
671D9, containing MeCP2 locus) probably escape inactivation in late replicating chromosome
X in some RTT patients. Therefore, region Xq28 could contain the genes escaping X
inactivation and with expression from the human active and inactive X chromosomes.
These results support the hypothesis proposing the disturbances in dosage compensation
effect due to aberrant activation of genes in inactive chromosome X in RTT (bi-allelic
expression instead of mono-allelic). Our results indicate that the normal allele of
the MeCP2 gene could escape X inactivation and reduce the pathogenic effect of mutated
allele in RTT.
Keywords
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© 2001 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
