Genomics and homeostasis.

The Cannon lecture this year illustrates how knowledge of DNA sequences of complex living organisms is beginning to shape the landscape of physiology in the 21st century. Enormous challenges and opportunities now exist for physiologists to relate the galaxy of genes to normal and pathological functions. The first extensive genomic systems biology map for cardiovascular and renal function was completed last year as well as a new hypothesis-generating tool ("physiological profiling") that enables us to hypothesize relationships between specific genes responsible for the regulation of regulatory pathways. Techniques of chromosomal substitution (consomic and congenic rats) are beginning to confirm statistical results from linkage analysis studies, narrow the regions of genetic interest for positional cloning, and provide genetically well-defined control strains for physiological studies. Patterns of gene expression identified by microarray and mapping of expressed genes to chromosomal sites are adding to the understanding of systems physiology. The previously unimaginable goal of connecting approximately 36,000 genes to the complex functions of mammalian systems is indeed well underway.