1. Is He Blind? A Visual Case By Eric Ribbens Western Illinois University

2. CQ1: Are there genetic diseases that we cannot cure? A. No B. Yes, but just a few C. Yes, but we have cures for most D. Yes, many of them E. Yes, many of them, and none we can cure

3. Scenario Neil is a 48 year old male who is nearsighted with a large blind spot in his left eye. When examined, a complete visual fields evaluation was performed.

4. How to Read A Visual Field The center of the graph is the focal point. Each ring shows the area where he can see a light. The innermost ring is the dimmest light, the outermost the brightest.

5. Neil’s Visual Fields

6. Small Group Problem: Describe Neil’s vision. Remember, you are a scientist: be as accurate and precise as possible! Don’t just say “He can’t see very well.”

7. CQ2: Neil’s vision is… A: He cannot see what he focuses on B: He cannot see much outside his focal area C: He cannot see movement D: He cannot see colors E: He can see well, he just doesn’t realize it

8. Small Group Problem: Describe Neil’s peripheral vision.

9. Neil has very limited peripheral vision. His left eye is better than his right eye. In his right eye he only has left some peripheral vision above his focal spot; in his left eye he has no peripheral vision to the left of his focal spot.

10. Peripheral Vision What do we use peripheral vision for? In other words, what couldn’t Neil see that a person with normal vision could see?

11. Peripheral vision provides contextual cues, shows movement of objects around the viewer, and is especially used in nighttime vision.

12. CQ3: So if Neil has very limited peripheral vision, you can predict that he cannot: A: See stars B: See movement C: See things that are far away D: See colors very well E: See out of a periscope

13. What does the big cutout on the left side of his left eye represent?

14. CQ4: The big cutout: A: Is the area where he still can see B: Is an area the doctor didn’t test C: Is an area where bacteria have damaged his retina D: Is an area where he can’t see anything

15. What does the big cutout on the left of his left eye represent? It is an area in which Neil can see nothing. This area is especially important because it covers an area outside the view of the right eye. Because he has no peripheral vision to the left, he is unable to sense anything moving at him from his left.

16. Group work: Why is he much less able to see a dim light than a bright light?

17. Why is he much less able to see a dim light than a bright light? Because it requires greater sensitivity of the pigment. One implication is that eventually things like a computer screen will appear brighter in the middle and dimmer around the edges.

18. Variety of Defects Retinitis pigmentosa is a syndrome caused by various genetic defects in the genes that code for the development of the pigments in the retina. Today we know of about 70 different genetic defects that can cause this. Why are there so many defects possible in these pigments?

19. Why are there so many defects possible in these pigments? I suspect it is due to the very precise configuration of these pigments that is required; many defects are possible in the way that these proteins are folded.

20. Sequencing If all of the pigments are slowly breaking down, why is his peripheral vision the first to go?

21. No one knows why peripheral vision deteriorates first. The pigment layer is as thick in the perimeter as in the focal area before the disease takes effect.

22. What do you think will eventually happen to his vision? Why? Hint: think about the possibilities: it could get better, it could stay the same, it could get worse. Given his history and what you know about the disease (genetic cause), answer this question.

23. What do you think will eventually happen to his vision? Why? Pigment loss will continue to happen. Eventually his vision will be restricted to his focal spot, and he may become legally (10 degree or less peripheral vision) or completely blind.

24. Genetic Counseling Build a Punnett Square showing the possible offspring of Neil’s parents. Hint: both parents are normal, and the disease is recessive.

25. CQ5: What are the chances that a sibling also has the disease? A. 0% B. 25% C. 50% D. 75% E. 100%

26. What are the chances that a sibling also has the disease? If it’s recessive, than both parents must be carriers (heterozygous). 50% chance of getting it from each parent, 25% chance of getting two copies.

27. More Genetic Counseling Let’s assume that 1 out of 50 people is a carrier for Usher’s Syndrome Type II. If Neil’s brother Paul does not show RP, what are the chances that Paul’s son has it?

28. Chances Paul’s son has it? First, we need to calculate the probability that Paul is a carrier. There are four possible combinations of gametes Paul could have received from their parents: RP (Dad) and RP (Mom) RP (Dad and normal (Mom) normal (Dad) and RP (Mom) Normal (Dad) and normal (Mom).

29. Chances Paul’s son has it? However, we know Paul doesn’t have RP so the first combination can be thrown out. Two of the other three combinations have one copy of the RP gene, so there is a 2/3 chance that Paul is a carrier.

30. Chances Paul’s son has it? 1: Paul 2/3 likely to be a carrier. Second, we need to know the probability that Paul’s wife is a carrier. We’re told this in the problem, 1/50. Third, we need to know the probability that two carriers have a child with both genes RP. We calculated that in CQ5: 1/4

31. Chances Paul’s son has it? Therefore, the chances that Paul’s son has RP is: 2/3 * 1/50 * ¼ = 0.00333 Note that this is for one specific son! If we rewrite the question as What are the chances Paul has a son with RP, then you need to multiply by the # of sons.

32. CQ6: What causes a genetic disease? A. Coding in the DNA in a chromosome B. A gene doesn’t get translated properly into a protein C. Something goes wrong inside your cells as you get older

33. Quick Review What’s RP? How do you read a visual field chart? How does it relate to the unit we are studying in this course? How did we calculate the probability of a nephew with RP?

34. FollowUp Neil was diagnosed with RP three years ago. His eyes have gotten worse. He is now legally blind, has stopped driving, and cannot play basketball anymore. He hasn’t seen stars for several years, but is grateful he can still see well enough to teach.