This is just the tip of the iceberg with this subject, but it is the quickest one for me to jot down a couple notes and be able to pitch some more paper laying around the house, so now, on to the controversial....

Megacolon...

During development, neural crest cells that originate along the embryo's back, migrate to other areas. Some of these neural cells are responsible for ennervating the colon. If this migration is delayed or disrupted, these cells do not get where they need to go, resulting in improper control of the colon.. in other words, megacolon can develop. The colon eventually fails as feces back up in the system, and a bloated, painful rat is the result. Megacolon is a fatal condition. This is not unique to rats, and is seen in mice, horses, ferrets, dogs, and even humans. They may not involve the exact same mutation, but the result is the same due to some interruption in normal cell migration to these areas of the body.

So, why the risk associated with distinct white patterns and spotting in the coat? Pigment cells also originate and migrate in the same manner as the neural cells, and even those in the inner ear, do during development. So, again, if there is a disruption, these pigment cells will not reach their destination either. You end up seeing the absence of pigment in the areas furthest from the neural crest, such as the face, stomach, feet, etc.

In rats, there are two known gene mutations that cause this. One is a recessive spotting lethal gene that actually results in a deletion of a gene that is responsible for melanocyte formations and cell dispersal in the intestinal region of the body. The result is an unpigmented forehead (a blaze typically) and a lack of normal nerve tissue in the colon, leading to megacolon. The other mutation is white spotting and this is a dominant gene. This mutation knocks out a protein that is responsible for many things, but particularly, in this case, is involved in melanoblast formation and migration. Its affect can be seen with a wide range of depigmentation from a blaze to a complete absence of color (black eyed white). These rats are also prone to anemia, reproductive problems, and deafness because of some of the other things the knocked out protein is responsible for (i.e. blood stem cell production, etc). In regard to megacolon, this particular protein is also involved in intestinal contractions and is critical for normal motility of the small intestine. This abnormal contraction of the intestines can be mild in these rats to severe, therefore megacolon.

Megacolon, although associated with 'high-white', can be caused by other factors as well, and the presence of 'high-white' does not always indicated megacolon either. Blazes and markings such as these can also be caused by other genes that do not affect, with their mutation, any of the elements that later cause intestinal issues. Efforts still continue to breed lines of blazed and marked rats with low to no incidence of megacolon, but much is yet to be learned.

References:
http://www.spflrc.org/user/rats/CoatColorMutations.htm
http://vtpb-www.cvm.tamu.edu/Larr_Mouse/pigment.html
http://www.spflrc.org/user/rats/megacolon.htm