Asynchronous replication of alleles in genomes carrying an extra autosome

Transcriptional activity of genes appears to be highly related to their rep lication timing; alleles showing the common biallelic mode of expression re plicate highly synchronously, whereas those with a monoallelic mode of expr ession replicate asynchronously. Here we used FISH to determine the level o f synchronisation in replication timing of alleles in amniotic fluid cells derived from normal foetuses and from those with either of the trisomies fo r autosomes 21, 18 or 13, or for sex chromosomes (47,XXX and 47,XXY). Two p airs of alleles, not associated with the extra chromosome, were studied in subjects with each trisomy and three in normal subjects. In cells derived f rom normal foetuses and from foetuses with sex chromosome trisomies, each p air of alleles replicated synchronously; yet these very same alleles replic ated asynchronously in cells derived from foetuses with trisomy for any of the three autosomes studied. The results suggest that the gross phenotypic abnormalities associated with an extra autosome are brought about not only by over-expression of genes present in three doses, but also by modificatio ns in the expression of genes present in the normal two doses.