Wednesday, December 7, 2011

Genotype and Severity

This comment was actually left on a blog titled Question From Reader: More Severe Genes? from back in June, but I wanted to be sure to share it as a blog so that everyone can get a little more insight into this issue. The comment was left by Jessica, a cyster in the community that is about 150 times smarter than your average bear. In fact, I generally don't understand what in the heck she's talking about (I know, big shock). If you would like to see the original blog, be sure to click the link above. 


There are actually six classes of mutations, and they don't directly range from 1-6 in "severity". Also, they don't indicate severity so much as the manner in which the CFTR protein and/or transport is faulty - a cellular issue that has not been proven to be affected by patient behaviors. There's a lot of great information with more detail and specifics in this article on the CFF website: 

Taking care of yourself - treatments, exercise, nutrition, etc, are all still extremely important to put yourself in the best position for optimum health, but none currently available have any direct impact on the cellular-level mutation problem itself - that's exactly where these new treatments come in and why they're so exciting! 

Lastly, a quick but important distinction: DeltaF508 is the most commonly identified mutation, but *double* DeltaF508 is a genotype, *not* a mutation. Everyone has two mutations, which are often not the same; the genotype identifies the pair, and their interaction with one another (which is arguably equally if not more important than the mutations individually). DF508 is the most *commonly identified*mutation, but DDF508 is not necessarily the most common *genotype*, and if it is, it's by a slim margin - it's not like there is a vast majority of double deltas and other genotypes are sort of "odd type out" in CF statistics. 

Also, while that DF508 is the most commonly *identified* mutation , many scientists argue that may just as well be because it was the *first* identified mutation, and as more mutations are identified AND more individuals learn their genotype, that will likely change, as it doesn't make sense that DF508 would be the most common from an evolutionary biology standpoint. 

The most important reason to know your (or your child's) genotype is because the new wave of treatments are all going to be rather class specific, if not mutation specific - knowing BOTH of your mutations lets you know whether new trials apply to you (so you can participate and get them to market quicker!) and if they don't, whether the science might be in the same wheelhouse and therefore might eventually - or at least more quickly than a treatment targeting a mutation in a completely different class.