Mutations. We know what they are. Mutations change a gene, which can change the protein. And this change in the protein can be either neutral, good or bad. Let’s finally talk about how these mutations can be bad.
There are over 4,000 diseases that are caused by mutations in just one gene. This means that if there is a mutation in one copy of the gene (if dominant) or both copies of the gene (if recessive), there is nearly 100% likelihood that you will get the disease. Let’s look at some common examples.
This is a genetic disease of the lung that is caused by a recessive gene called the cystic fibrosis transmembrane conductance regulator (or CFTR for short). This gene makes a protein that transports chloride across the cell membrane. The most common mutation in this gene is a deletion that causes a frameshift, which makes a much shorter protein. This shorter protein doesn’t work properly at transporting chloride and results in fluid build up in the lungs and other organs that leads to cystic fibrosis (also known as CF).
Since this is a recessive disease, what this means is that you need TWO copies of the mutated CFTR gene to get cystic fibrosis. Remember those genetic squares we used to figure out what the possibility of a child inheriting a particular allele of a gene? Let’s look at one for CFTR. If you imagine that the normal CFTR gene (the one that isn’t mutated) is “C” (shown in blue) and the mutated CFTR gene is “c” (shown in orange). If each parent has one copy of the non-mutated and one copy of the mutated CFTR gene Cc, then they have a 25% chance of having a child with CFTR. Why? Because only a child with two copies of the recessive trait (which in this case is the mutated CFTR gene) will have cystic fibrosis.
This is an example of a dominant mutation that causes a disease. The huntingtin gene
has a region that has lots of repeats of one codon CAG. Most people have less than 36 repeats of CAG. However, if a person has more than 36 repeats, it creates a protein that is toxic to brain cells – exactly how and why it is toxic isn’t really well understood. Since this is a dominant mutation, you only need one copy of this mutated gene to get Huntington’s disease. So if you have one parent with the Huntingtin mutation (shown as H*), which means they have one copy of the Huntingtin gene with >36 CAGs, then a child has a 50% chance of also inheriting Huntington’s disease (HH*)
Now you may be wondering, how do we know if the mutation will be dominant or recessive? That’s a complicated question. In part, you may know if you look at the family history. A disease caused by a dominant mutation will be inherited by more often by the children of an affected parent whereas a recessive mutation is less likely to be inherited because it is only inherited when both parents have one copy of the recessive gene. Another option is to study the function of the mutation protein and see how the mutation in the gene affects the function of the protein. Since there are two copies of every gene, if one copy is mutated, the second copy of the gene could compensate for this mutation (in the case of cystic fibrosis). In other cases, the mutation could cause such dysfunction that even with the normal protein around, it still causes disease (like Huntingtin’s).