Michael G. Walker
Wayne Volkmuth
Tod M. Klingler
Abstract
We wish to identify genes associated
with disease. To do so, we look for novel genes whose expression
patterns mimic those of known disease-associated genes, a method
we call Guilt-by-Association (GBA). GBA uses a combinatoric measure
of association that provides superior results to those from correlation
measures used in previous expression analyses. Using GBA, we have
examined the expression of 40,000 human genes in 522 cDNA libraries,
and have identified several hundred genes associated with known
cancer, inflammation, steroid-synthesis, insulin-synthesis, neurotransmitter
processing, matrix remodeling and other disease genes. The majority
of the genes thus discovered show no significant sequence similarity
to known genes, and thus could not have been identified by homology
searches.
We present here an example of the discovery of five genes associated with schizophrenia and Parkinson's disease. Of the 40,000 most-abundant human genes, these five genes are the most closely linked to the known disease genes, and thus are prime targets for pharmaceutical intervention.