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Human Molecular Genetics Advance Access published online on January 20, 2004

Human Molecular Genetics, doi:10.1093/hmg/ddh062
© 2004 by Oxford University Press
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©2004 Oxford University Press

Article

Coordinated replication timing of monoallelically expressed genes along human autosomes

Alexander W. Ensminger 1 and Andrew Chess 1*

1 Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, U.S.A.; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, U.S.A.

* To whom correspondence should be addressed. E-mail: chess{at}wi.mit.edu.


   Abstract

A number of genes in the mammalian genome are expressed from only one of two alleles in either an imprinted or random manner. Those belonging to the random class include X-linked genes subject to X inactivation, as well as a number of autosomal genes, including odorant receptors, immunoglobulins, T-cell receptors, interleukins, natural killer-cell receptors, and pheromone receptors. Monoallelically expressed genes display the unusual property of asynchronous replication and for those genes whose transcription is randomly monoallelic, the asynchronous replication is also random. In mice, recent work has shown that the random asynchronous replication of distributed autosomal genes is coordinated at the whole chromosome level, indicative of chromosome-pair nonequivalence. Here, we show that autosome-pair nonequivalence is present in human cells, and demonstrate its ability to cross the centromere. Additionally, by examining the replication of these genes in a number of human trisomies, we consistently find one allele replicating early and the other two alleles replicating late, similar to previous observations in X trisomies.


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