Comparison of human sequences with the DNA of other mammals is an excellent
means of identifying functional elements in the human genome. Here we desc
ribe the utility of high-density oligonucleotide arrays as a rapid approach
for comparing human sequences with the DNA of multiple species whose seque
nces are not presently available. High-density arrays representing similar
to 22.5 Mb of nonrepetitive human chromosome 21 sequence were synthesized a
nd then hybridized with mouse and dog DNA to identify sequences conserved b
etween humans and mice (human-mouse elements) and between humans and dogs (
human-dog elements). Our data show that sequence comparison of multiple spe
cies provides a powerful empiric method for identifying actively conserved
elements in the human genome. A large fraction of these evolutionarily cons
erved elements are present in regions on chromosome 21 that do not encode k
nown genes.