Question

1) The spike protein on the surface of SARS-CoV-2 virus particles interacts with the ACE2 protein on our cells to initiate infection. The protein, TMPRSS2, then cleaves the spike protein allowing the virus to enter the cell. This leads to both cell death via pyroptosis and a widespread inflammatory response that damages the lung infrastructure.

Scientists have identified a mutation in the TMPRSS2 gene that reduces viral entry in mice. Infected cells with the tmprss2 mutation make TMPRSS2 protein that is unable to cleave the spike protein. Based on this information the mutation is most likely Loss of Function.

a) Is the tmprss2 mutation described in more likely to be dominant or recessive? Recessive

b) Given that the tmprss2 mutant allele described in (a) contains an insertion, how would the results obtained using PCR be used to support your answer?

Answer 1

a) Considering it is a loss of function mutation it is most likely a recessive mutation. Most of the loss of function mutations are recessive, due to the phenomenon in which if one allele loses its function, the other allele still is able to get expressed and acomplish the function.

Not ethat there are some exceptions for that, but they are not common

b) Well, a PCR will amplify the both copies in the genome, whether they are the wildtype or our mutated case. We have to take samples from both cells that ARE NOT able to cleave the spike protein and cells that ARE able to cleave it. When analyzing the cellss that are able to cleave it, if we find 2 possible genotypes, one in which there is only one band with the normal size of the tmprss2 gene, and another one with 2 bands one with the normal size and another with a smaller size (the deletion mutant), then we confirm our answer of it being recessive.

BUT, if when analyzing the cells that are NOT able to cleave the spike we find 2 genotypes, one with one single band that corresponds to the size of the deletion mutation, and another one with 2 bands one with the normal size and another with a smaller size (the deletion mutant), then the PCR confirms we were wrong in our answer.