As a World-famous medical doctor that dabbles in research from time to time, you’ve taken a recent interest in a newly discovered compound that appears to cure terriblitis, which has a variety of terrible symptoms. However, this drug appears to work in only 33% of patients, while the remaining 67% seem completely immune to the drug. You head to your basement lab with your data to solve the mystery.
1. You have complete family history for a large family in which every family member is affected by terribilitis. You’ve constructed a family tree to discern the heritability of the drug-susceptibility phenotype.
a. The shaded boxes indicate individuals that were cured by the new drug. The clear boxes indicate individuals for whom the drug had no effect. (Dark grey boxes indicate individuals that have not been tested.) The individual marked with the arrow is called the ‘propositus’, or the individual under study. Based on this information, do you believe the father of the propositus could be curedby the drug?Why or why not?
b. Based on the father’s predicted genotype, what is the probability that the propositus could be cured with the drug?
2. Using standard molecular techniques, you determine that the limaglobingene is responsible for drug susceptibility in this case. The sequence of the dominant and recessive alleles is shown below. The sequence of the propositus is also shown (two alleles, as the individual is human and thus diploid). Based on this data, will the propositus be able to be cured with the drug?
Dominant allele: 5′-AATAGACAGTACAGTAGGGACCGTGAGTTTAGTAG-3′
Recessive allele: 5′-AATAGACAGTACAGTAGGGACTGTGAGTTTAGTAG-3′
Propositus allele 1: 5′-AATAGACAGTACAGTAGGGACCGTGAGTTTAGTAG-3′
Propositus allele 2: 5′-AATAGACAGTACAGTAGGGACTGTGAGTTTAGTAG-3′
3. Based on the data given in Q2, you choose to confirm with a restriction digest using an enzyme (CutII) that cuts the recessive allele on the 5′ sideof the mutation. The dominant allele is not cut by this enzyme. Based on this information, draw the bands in the gel below. Use the laIDer given to determine how far the fragments will travel on the gel.
4. Assuming that the DNA sequence in Q2 is in frame and shows the TEMPLATE strand. Determine the amino acid sequence using the genetic code and give a chemical explaination as to why the drug binds better to the recessive allele. (Hint: remember that mRNA is produced 5′ to 3′, which means that the DNA is read 3′ to 5′.).
5′-AATAGACAGTACAGTAGGGACCGTGAGTTTAGTAG-3′
5. You decide to expand your study to a much wider population. You study 1000 individuals of various genotypes to see if they are receptive to the drug. You then test their genotypes. Is your data consistent with the hypothesis that the trait is strictly Mendellian with complete dominance? (3 points)
|
Genotype RR |
Genotype Rr |
Genotype rr |
Receptive to the drug |
206 |
275 |
53 |
Not receptive |
90 |
26 |
350 |
(Note: You will need to conduct a Chi-squared test. Complete each of the following parts to do your test).
Ho:
Ha:
Degrees of freedom:
X2 value:
|
Expectation |
Observation |
Not cured (RR or Rr) |
|
|
Cured (rr) |
|
|
Because the chi-squared value is (greater than / less than) my critical value, I will (reject / accept) the null hypothesis.
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