Human chromosome 21 gene expression atlas in the mouse.

The study of gene expression patterns is of crucial importance to the understanding of gene function. We set out to systematically analyze the expression patterns of genes from an entire chromosome. We chose human chromosome 21 (HC21) because its entire finished nucleotide sequence was available. Furthermore trisomy 21 (Down syndrome, DS) is the most common genetic cause of mental retardation. This chromosome-based approach has advantages over the study of an arbitrary set of genes, as it provides information on the consequences of aneuploidy, and may allow the identification of clusters of co-regulated genes. All identifiable murine orthologs of human chromosome 21 genes (161 out of 178 confirmed human genes) were analyzed by RNA in situ hybridization on whole-mounts (E9.5, E10.5) and tissue sections (E14.5), and by RT-PCR on adult tissues. These stages correspond to mid and late embryonic and fetal human periods, when the major organs and body regions are organized. Patterned expression was observed in several tissues including those affected in trisomy 21 phenotypes (i.e. CNS, heart, gastrointestinal tract, and limbs). Furthermore, statistical analysis suggests the presence of clusters of genes with significant patterns of either coexpression or lack of expression in specific tissues. The entire data set was incorporated in a web site that will be made available to the scientific community. This high resolution expression "atlas" of an entire human chromosome is a new level of gene annotation, which is likely to advance our knowledge on gene function and regulation and to the understanding of human aneuploidies, such as DS.