GENETIC-DIVERGENCE BETWEEN MOUSE AND HUMANS - A USEFUL DIRECTION FOR GENE PATHWAY ANALYSIS

Preliminary results in comparative genetics have revealed a growing li st of differences between mice and humans (Strachan et al. [1997]: Nat . Genet. 16:126-132). However, it is increasingly apparent that some o f these differences ave not accompanied by changes in function. Such d ifferences are nevertheless useful because they represent a sort of ge netic experiment that provides evidence helpful in deducing how the ge netic circuits work. This article draws attention to some recent resul ts. First, we briefly report on representative examples of genetic dif ferences between rodents and humans, suggesting, as expected, that suc h divergence is abundant and diverse at all levels of gene regulation. Second, on the basis of a more detailed analysis bearing on four exam ples, we emphasize that the study of genetic differences associated wi th little or no functional divergence is likely to be a profitable dir ection for future analysis of genetic pathways. Finally, we suggest th at apparently nonfunctional genetic divergence may underlie different susceptibilities to disease. A detailed knowledge of human-mouse genet ic divergence will provide an indispensable framework for extrapolatin g the molecular effects of mutations and teratogens from mice to human s in studies of abnormal development. Teratology 58:82-87, 1998. (C) 1 998 Wiley-Liss, Inc.