Down syndrome is the most common cause of mental retardation in humans. Through a yet unknown mechanism, the presence of an extra copy of human chromosome 21 (HSA21) causes developmental defects in many organs, most notably the brain. HSA21 was the second human chromosome to be fully mapped and sequenced, and now two groups report the first comprehensive analysis of the expression patterns of HSA21 genes in the mouse. These 'atlases' promise to be a valuable resource for identifying the genes that underlie Down syndrome.

The two groups — Reymond et al. and The HSA21 Expression Map Initiative — identified the mouse orthologues of the 213 genes on HSA21, of which 178 are confirmed, and isolated cDNA fragments corresponding to these genes. Then, using complementary approaches, they looked at their expression in different tissues and at different developmental stages of mouse embryogenesis using reverse transcriptase PCR and mRNA in situ hybridization. In addition to this 'wet bench' approach, The HSA21 Expression Map Initiative relied heavily on informatics to measure their frequency in publicly available mouse EST libraries and to identify genes with similar expression profiles. They also conducted mRNA in situ hybridization, focusing on whole embryos and on the neonatal brain. Both groups have deposited their data in a web interactive database.

Together, these studies highlighted several HSA21 genes that, because of their expression in the tissues and organs that are most severely affected by Down syndrome, are good candidates for further investigation. Interestingly, the expression of many HSA21 genes is ubiquitous in early embryogenesis, but becomes more restricted as development proceeds. This is consistent with findings by The HSA21 Expression Map Initiative, who showed that genes found exclusively in multicellular organisms are more likely to be expressed in a spatially or time-restricted pattern, compared with the ubiquitous expression of those genes that are also found in yeast. Both groups also observed genes with similar expression patterns that cluster on particular chromosome regions, as recently reported in worms and flies, which hints at how chromatin structure might govern gene expression.

Mapping the gene expression of an entire chromosome at high resolution provides the next level of genome annotation and brings researchers closer to identifying the function of every human gene — the most important issue in genomic biology.