Prions are self-propagating infectious protein isoforms. A growing number of 
prions have been identified in yeast, each resulting from the conversion of 
soluble proteins into an insoluble amyloid form. These yeast prions have served 
as a powerful model system for studying the causes and consequences of prion 
aggregation. Remarkably, a number of human proteins containing prion-like 
domains, defined as domains with compositional similarity to yeast prion 
domains, have recently been linked to various human degenerative diseases, 
including amyotrophic lateral sclerosis. This suggests that the lessons learned 
from yeast prions may help in understanding these human diseases. In this 
review, we examine what has been learned about the amino acid sequence basis for 
prion aggregation in yeast, and how this information has been used to develop 
methods to predict aggregation propensity. We then discuss how this information 
is being applied to understand human disease, and the challenges involved in 
applying yeast prediction methods to higher organisms.