What does it mean if I’m a “carrier”?

What does it mean when someone “carries” anything?  The definition of “carry”is to hold or support something while moving somewhere.  Often when you carry something it’s heavy, a burden.  When you’re a genetic carrier, it’s much the same.  You’re holding or supporting a recessive gene mutation as you move around in your normal everyday life.  Even though the recessive gene doesn’t affect you, it’s a genetic burden, because you could pass the trait down to your child.

cfLet’s remind ourselves what it means to have a recessive gene (or re-read the original post referencing 50 Shades of Grey).  You have two copies of every chromosome, and on each of these chromosomes is copies of each gene (called alleles – pronounced AL-eels).  These genes can be slightly different.  In some cases they are different enough that one copy doesn’t work as expected or work at all (these are the “recessive” genes we talked about in an earlier post).  Often the functional copy of the gene can compensate for the copy that doesn’t work right.  But in the case where both copies of the gene don’t work correctly, the person can end up with a disease.  The example that we used previously was cystic fibrosis.  A person will have cystic fibrosis only when the have two copies of the mutated CFTR gene.  The same is true for sickle cell anemia, which is caused by having two mutated copies of the hemoglobin gene called HbgS.  If a person only has one copy of HbgS, the other normal hemoglobin can produce enough hemoglobin to function just fine.  However, if there are two copies of HbgS, the HbgS protein structure collapses in cases where the person doesn’t have enough oxygen and this causes the red blood cells to make a sickle shape.
youandpartnercarrierThere are a number of diseases that are caused by having two copied of a mutated recessive gene (many are listed here).  But again, if you only have one copy, you’re just fine – but you carry that gene mutation. If you have children with someone else who is a carrier (meaning that they also have one copy of a recessive gene that would cause disease), then you have a 25% chance of having a child with that disease, because they have 25% chance of getting two copies of the recessive gene.

This isn’t a huge deal – only 25%, right?  Except that you would never know from looking at someone if they are a carrier.  And you wouldn’t know from living with yourself for all these years if you are a carrier.  And some populations or ethnic groups are more likely than others to be carriers for recessive genes for certain diseases. If you look at the chart below, I have listed a few ethnic groups and diseases which they are often genetic carriers.  After the name of the disease, I have listed the likelihood of someone from that ethnic group being a carrier for a recessive gene that would cause that disease. For Caucasians, if you and 28 people are sitting in a room, one person would carry a mutation in one copy of the CFTR gene that would cause cystic fibrosis. It is estimated that at least one in five Eastern European Ashkenazi Jewish individuals is a carrier of one gene that would cause a genetic disorder.

carrierSo what should you do now that you know that you could be a carrier for gene that could cause a disease.  There are options – the first one being doing nothing at all.  You could also look at your family history.  Are there people in your family or your partners family with a recessive genetic disease like Wilson Disease or Tay-Sachs?  If so, you may want to get tested for common recessive genes. On the other hand even without family history, if you are from a particular ethnic group such as Ashkenazi Jew, you may be encouraged to get tested no matter what (see an interesting guidance about this here) before or during pregnancy.  There is also the possibility that you want to be prepared, and before you and your partner get pregnant that both of you are tested for common carriers. Next post, we’ll talk more about what you can do if you are a carrier.

 

 

 

 

What are examples of diseases caused by one gene?

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.

Cystic Fibrosis

cfThis 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.

Huntington Disease

This is an example of a dominant mutation that causes a disease.  The huntingtin genehuntingtin
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).