Coordinated replication timing of monoallelically expressed genes along human autosomes

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 non-equivalence. Here, we show that autosome-pair non-equivalence 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.