An article in the NYTimes last week talks about research with fruit flies that supports the idea of multiple gene frequencies changes over generations leading to change (evolution) and not the idea of big infrequent mutations leading to change. The article termed this "soft sweep" and it makes sense given mutation rates and the chances that a mutation is positive rather than neutral or detrimental to an organism. This is not to say that mutations don't give rise to change (they do), but rather that they do not seem to be the norm.
This research also supports the concept of many genes controlling traits, as opposed to just a single gene for each trait. This is becoming a focal point of disease research. While some diseases may be controlled by a single gene, some diseases are likely subject to control by a whole slew of seemingly unrelated genes. This is why certain disorders may run in families, but have no discernible genetic basis. It makes it very difficult then to access how at risk someone is for a certain disorder, and since environmental factors definitely play a role in gene expression, it could be extremely hard to predict an individuals likelihood for a specific disease.