1. Welcome to Week 5! Today: Gene Interactions
Thursday: Gene Interactions in Autism
Reminder: Check online for a list of your presentation due dates!

2. Gene Interactions: Why might 2+ genes interact? Biosynthetic pathways?
Signal- transduction pathways?
Developmental pathways?

3. Gene Interactions: How do you know when 2+ genes interact?
Look for protein: protein interactions
Analyze patterns of transcription
Forward genetics!

4. A Simple Place to Start: Interactions Between Alleles of a Single Gene
If this gene is haplosufficient, is the mutation dominant or recessive? What if it is haploinsufficient?

5. A Simple Place to Start: Interactions Between Alleles of a Single Gene
What’s a dominant negative?

6. A Simple Place to Start: Interactions Between Alleles of a Single Gene
Incomplete Dominance

7. A Simple Place to Start: Interactions Between Alleles of a Single Gene
What do you need to see to demonstrate codominance?

8. A Simple Place to Start: Interactions Between Alleles of a Single Gene
Note that this distinction is often a question of scale!

9. A Simple Place to Start: Interactions Between Alleles of a Single Gene
Why are geneticists excited to find lethal alleles?
What happens to your ratios with a lethal allele? What if it’s sublethal?

10. Gene Interactions in Pathways: Beadle and Tatum

11. Gene Interactions in Pathways: Beadle and Tatum
Checking in on the Homework:
Mu-tant
Com-pound A
Com-pound B
Com-pound C
Com-pound D
Com-pound E
Com-pound G 1 - + 2 3 4 5
This is the classic approach to finding gene interactions! Mutants are then compared pair by pair. If double mutants have a unique phenotype then interaction is inferred.

12. Gene Interactions in Pathways: Beadle and Tatum
Let’s Practice!
Mutant
Com-pound 1
Com-pound 2
Com-pound 3
Com-pound 4
Com-pound 5
“Ann” + -
“Suzanne”
“Ruben”
“Oscar”
With your neighbor, identify the most probable order of compounds in the pathway.
Identify where each mutant is blocked in the pathway.

13. Complications!
How do you know if two mutants have different mutations in the same gene?
Imagine you’ve isolated two separate, recessive, wingless mutant Drosophila. You conduct a complementation analysis by crossing one mutant fly to the other. What will you see if these mutations are both in the same gene? If they’re in different genes? Draw Punnett squares or branch diagrams to illustrate your results.

14. What can a double mutant tell us?
Complications!
What can a double mutant tell us?
Assume the genes from our wingless mutants did complement, suggesting we have two separate genes. If you cross two of these F1, winged flies, what fraction of the F2 generation would you expect to be double mutants? Show your expected results in branch diagram!
What will genotypes do you expect in the progeny? What will the phenotype ratio be?

15. Interpreting F2 Ratios:
9: 3: 3: 1?
9: 7 ?
9: 3: 4 ?
12: 3: 1?
No gene interaction!
Genes in the same pathway
Recessive epistasis
Dominant epistasis

16. What is Epistasis?

17. Other Unusual Gene Interactions:
What’s wrong with this pedigree?
With your neighbor, identify the inconsistent individual.
Propose a mechanism (other than the mailman!) to explain this inconsistency.

18. Hint: An enzyme called fucosyltransferase is required to modify the precursor to produce the A or B antigen. The gene for this enzyme is haplosufficient.

19. Gene Interactions: Suppressors
What is a suppressor?
How can you distinguish a suppressor from a revertant?
What phenotypic ratio would you expect to see if you crossed a suppressed mutant with a wild-type Neurospora?

20. Gene Interactions: Penetrance and Expressivity
How do I distinguish these two?