Module 2: Homework
Christopher A Schmitt
September 24, 2020
Homework: Introduction to Hardy-Weinberg Equilibrium
Readings:
- Chen J. The Hardy-Weinberg Principle and Its Applications in Modern Population Genetics. Frontiers in Biology 5(4): 348-53.
- Benetti E, et al. 2020. ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population. European Journal of Human Genetics
- Maekawa et al. 2014. TMPRSS2 Met160Val polymorphism: Significant association with sporadic prostate cancer, but not with latend prostate cancer in Japanses men. Int J Urology 21(12): 1234-1238
- Wigginton JE, Cutler DJ, Abecasis GR. 2005. A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 76: 887-893.
Now that many of us have a little more facility with working with Ensembl and 1000 Genomes data, I’m hoping this week’s lab homework will be fairly simple. Don’t forget: for more conceptual questions, you can consult both your notes/slides from lecture and the textbook!
As before, you’ll be turning in your homework via an online interface. I recommend writing your essays in a document on your laptop and only engaging with the online interface when you’re ready to turn in all of your completed answers.
What does it mean if there is a SNP in the gene ACE2 or TMPRSS2 that is not in Hardy-Weinberg equilibrium? Think not only about the phenotypic consequences, but what it says about the environment of the population.
How many SNPs in your population were out of Hardy-Weinberg equilibrium?
Please list each of the four SNPs you chose to check for “true” Hardy-Weinberg equilibrium using the Shiny App embedded in the Lab 2 tutorial. What was the P-value of each using the R analysis? What was the modified P-value using the Shiny App? Did any of them change significance? Based on the Module 2 tutorial and the Wigginton et al. (2005) reading, what does a change in P-value mean?
Imagine that gene map above represents ACE2. Based on the Benetti et al. (2020) article itself, and what you know about the organization of genes and the cDNA for the transcript ACE2-201 on Ensembl, where in a gene map for ACE2 would you find the SNP Lys26Arg (e.g., intron 1-2, exon 3, 3’-UTR, promotor, etc)?
Where on the map above is the SNP in your population that most significantly deviates from Hardy-Weinberg equilibrium? How would you predict that SNP might affect ACE2 or TMPRSS2 phenotype? If you don’t have any SNPs that deviate, choose one at random.
Think about the economic, cultural, and medical context of your 1000 Genomes population. Would it make sense for your population’s ACE2 or TMPRSS2 genotype/phenotype to be influenced by evolutionary forces under the current pandemic? Why or why not?
Remember: further questions on hand-written HWE calculations from Lecture 6 will also be accessible in the homework submission interface!