Question: if two parents have the gene for cf what is the chance that their child will get it?

Tim Downing answered on 15 Nov 2012:

Hi Roisin,

Everyone has the gene that is mutated in cystic fibrosis patients called CFTR. The CFTR gene makes a big protein that sits in our cell membranes, like a gate in a fence. It does this for many cells, including ones in our digestive system. So when we eat things like salt that have a lot of a natural chemical called chlorine – this protein lets this chlorine in and out of the cell. If the cell thinks it needs more chlorine from the bananas you ate, then the big CFTR protein lets more chlorine in. And then likewise if the cell thinks it has too much, it sends some of the chlorine atoms out. We then release this excess chlorine naturally, like in our sweat. So everyone has this gene.

We all inherit 2 copies of the gene, one from each of our parents. If one copy has a bad mutation so that it doesn’t send the chlorine into or out of our cells as well as normal, the other good copy will do this enough so that one bad CFTR copy does not matter. Remember that this is only for bad mutations – we all have lots of mutations that make us unique, but most of them have no effects. These are called neutral mutations, and like the bad mutations we also have good mutations that give us an advantage. So many mutations in CFTR genes have no effect, and also a few bad ones also make people ill with cystic fibrosis but also with some other rarer diseases. This is because the CFTR protein is in many parts of our body where it regulates cell chlorine content.

So if two parents each had 1 faulty copy of the CFTR that gave rise to mis-folded CFTR proteins, there is a 25% chance that their child will have both bad CTFR copies. However, this does not necessarily mean they will have CF. Sometimes the mis-folding is only very minor, or other proteins can compensate. This depends on the type of mutation – over 1700 different mutations (so far!) have been detected in the CFTR so there are lots of different outcomes for these different types. This is good news because it means the actual chances of having CF is less than 25%.

Ireland has a really interesting contribution to make on the genetics of cystic fibrosis. Scientists have always wondered why CF is so common? One hypothesis is that having only one slightly faulty copy out of the two CFTR genes might give some people an advantage. The idea is that the reduced chlorine entry/exit associated with faulty CFTR gene copies might be useful because some bacteria use CFTR to get inside cells. Like many north European countries, Ireland has higher rates of CF than the rest of the world, which is why it is studied here – scientists Prof. Dan Bradley and Dr. Valeria Mattiangeli at Trinity College in Dublin have evidence it may be useful for us. But how is still a big question. I did my final year genetics project with these two researchers, and we examined Irish people CFTR genes … we didn’t quite find the answer to this big puzzle, but maybe you can?

Tim