There are lots of new terms at the start of medical school but two terms – penetrance and expressivity – seem to cause undue stress and confusion. One of the first areas of learning for the students is genetics, hopefully because it is central to understanding everything. Is the confusion due to being overwhelmed, strange associations or …?
I think it is easy to tell the terms apart – is this expert bias?
I’m sure there are fancy ways to describe penetrance and expressivity but my simple explanations:
Expressivity – how does a disease (or trait) show up?
As example, let’s took at two types of colon cancer. These terms are often used when discussing cancer. (Note: I’ll have to explain inheritance of cancer mutations later.)
- Familial Adenomatous Polyposis Coli (FAP) – 100% penetrant
- If you inherit the disease mutation, you will get the disease (provided you live long enough into adulthood)
- Hereditary Non-Polyposis Colorectal Cancer (HNPCC) – 80% penetrant with variable expressivity
- If you inherit the disease mutation, there is an 80% chance that you will get the disease (provided you live long enough into adulthood)
- Variable expressivity: HNPCC can also show up in other systems: uterine cancer is common but also cancer of the stomach, small intestine, pancreas, ovary, kidney and ureter.
So, does that make sense? Are the terms confusing? If so, please let me know!
If it isn’t confusing, why are the terms mixed up?
Hypothesis 1: the terms are always introduced together and so the students just mix them up
Several students seem to suggest this as an explanation. “It is just hard to remember the terms.”
Hypothesis 2: the terms are ambiguous
Some students say that penetrance makes sense but then get confused when they think about expressivity. Their logic – a gene is expressed when it is on so expressivity must mean on or off. This year, I addressed this reasoning in my workshops and it seemed to help some students.
Hypothesis 3: there is too much to remember
Several students have said that those terms are just the first ones to be ‘too much’. They also don’t use the terms much so they remain memorization terms. I strive for understanding in my workshops but I do realize that memorization happens.
Hypothesis 4: genetic anxiety
I often teach students who are new to genetics or have some anxiety. These anxious students can bring in some baggage from a previous poorly taught/understood course. Some of these students seem to make the terms harder than is needed for medical genetics. The NCBI reference even seems more complicated than needed. (Of course, maybe my explanation is too easy)
Any other reasons?
LisaM says
I really like your hypotheses about why students get confused. The language and the subtle differences between penetrance and expressivity do make it confusing! I agree the NCBI site is a bit complicated, however I did like these two parts for clarifying “thus penetrance is defined as the percentage of individuals with a given genotype who exhibit the phenotype associated with that genotype.”. I also liked thinking about it like this: penetrance is dependent on a yes or no answer (yes phenotype shown or no), where as expressivity is the shades of yes…..little, lots, etc. Is it fair to say that without expressivity is dependent on penetrance (at the individual level)?
genegeek says
Thanks for the comment! I like the point that penetrance is yes/no whereas expressivity is shades of yes.
For your last question, are you asking if expressivity is dependent on penetrance (how it shows up is dependent on IF it shows up)? I think so…
LisaM says
Thanks for the post, I’ll add it as a link to the course website for students to get some clarification on this topic!
Mark says
It’s hypothesis 2. That’s exactly how I felt!
Mai LEe Yang says
Great definition and examples. I think the examples definitely clears it up!!! 🙂
afeefah says
thank you , very helpful!