What is a genotype?

Information for children, teenagers and families

What is a genotype?

The genetic code inside every cell is made up of genes. Genes are turned into proteins in the cells and it is the proteins that carry out the work of the cells and make us who we are. Each gene has 2 copies - for the most part one of these is a spare, in case the first one goes wrong. This is the case in cystic fibrosis. CF is caused by one particular gene called CFTR (the cystic fibrosis transmembrane conductance regulator) not working properly. To have CF, both copies of the CFTR gene must be broken. There are lots of ways in which the gene can be broken, each of which has a name called a mutation. For CF to occur there must be a mutation in both copies of the CFTR gene. The genotype is the name given to these combinations of 2 mutations. The commonest mutation is called dF508 and the commonest genotype (found in half of all CF patients in the UK) is to have 2 versions of CFTR damaged by the dF508 mutation - usually written as 'dF508/dF508'. For a few mutations (the commonest of which is called R117H) there is some residual function of the gene, which means that the disease may be less severe than usual. For the majority (90%) of mutations however, the damage to the function of the CFTR gene is severe and doesn't vary for one mutation to another.

Genotype-specific therapy

Since the majority of genotypes end up with the same result on CFTR function and the same severity of CF, knowing the genotype for most people with CF did not, in the past, make any difference to therapy. This all changed in 2013 when a new drug called Ivacaftor became available. This drug is able to restore the function of CFTR but only for patients with particular genotypes - called gating mutations (eg G551D). It is likely that other treatments that are genotype-specific will be developed - hopefully for the common dF508 genotype - and this means that everyone now needs to know their genotype. Orkambi (lumacaftor-ivacaftor), which has been licensed in the US for use in patients with 2 copies of the dF508 mutation has not been funded for use in the UK (see the research section).

Know your genotype

We know the genotype (both mutations) of 99% of children in the OCCFN and we will make sure that all genotype-specific therapies are used as soon as they are available. Ask at your next clinic appointment if you want to know what your genotype is.