17 Genetic make-up
So what can we say about the genetic make-up of the individuals we tested?
In performing these PCR tests, there are some important aspects of human genetics that you will need to consider when interpreting your experimental data.
For each individual you have been able to determine:
- the overall copy number of the CYP2D6 gene present in individuals
- the number of CYP2D6*4 variant genes present.
Whilst this combination of data gives you some important information on those individuals, you must remember that you have only tested for two genetic variants.
For some individuals you do, in fact, have complete genetic data. For example, in individuals who carry two copies of CYP2D6, both of which are the *4 variant, you can confidently state that these individuals will not produce any CYP2D6 protein. In contrast, you will have identified some individuals with 3 or 4 copies of the CYP2D6 gene, none of which are the *4 variant. In this case, we do not, however, know whether each of their 3 or 4 genes are actually functional versions, or whether they carry other variants that inactivate the protein. In order to determine this, further testing is required to determine the DNA sequence of each of their CYP2D6 genes.
Once you have data for both CYP2D6 *4 and CYP2D6 copy number, look at the three samples you focussed on above (Samples 32, 33 and 34 in population A).
What can you say about the genotype for each individual? What can you say about that individual’s ability to metabolise prescription drugs that are processed by the CYP2D6 protein?
Answer
Sample 32 has no copies of the gene so this individual won’t produce any CYP2D6 protein and so won’t be able to metabolise certain prescription drugs.
Sample 34 has 2 copies of the gene, both of which are the CYP2D6 *4 variant. This individual won’t produce any functional CYP2D6 protein and so also won’t be able to metabolise certain prescription drugs.
Sample 33 has 2 copies of the gene, one of which is the CYP2D6 *4 variant. We don’t know whether the other copy is a functional version of the gene or whether it is another variant which produces faulty or no protein. We aren’t able to say whether this individual will be able to metabolise certain prescription drugs, but they would certainly have reduced ability compared to an individual with 2 or more functional copies of the gene.
Another thing that these tests don’t tell us is the make-up of each chromosome. For example a person with 2 copies of the gene, one of which is the *4 variant, might have 1 copy on each chromosome or they might have 2 copies on one chromosome and no copies on the other. So these tests can’t be used to answer questions about what genes that person might pass on.
16 Collected data