1. 1 The Genetics of Color- Blindness Dr. Rick Hershberger http://www.rickhershberger.com

2. 2 The Genetics of Color- Blindness Outline How our Eyes See Colors Defects in Human Color Vision A Gene for Red-Green Color Blindness Inheritance X-Linkage Pedigree Analysis -Testing my Daughter’s Prom Date?

3. 3 The Genetics of Color- Blindness Anatomy of an Eyeball

4. 4 The Genetics of Color- Blindness The Retina Contains Two Types of Light-Detecting Cells Rods – “See in shades of grey” -Cannot distinguish different wavelengths (colors) of light. -More sensitive to low light. Used for night- vision. Cones – “See in colors” -Three types of cones; differ in which photoreceptor protein (opsin) they make. -L-cones sense long-wavelength (red) light -Make the long-wavelength opsin protein -M-cones sense medium-wavelength (green) light -Make the medium-wavelength opsin protein -S-cones sense short-wavelength (blue) light -Make the short-wavelength opsin protein

5. 5 The Genetics of Color- Blindness Photoreceptor Proteins

6. 6 The Genetics of Color- Blindness How Color-Blind People See Things What people with normal color vision see. What a red-green color-blind person sees.

7. 7 The Genetics of Color- Blindness Types of Color Vision Deficiencies Trichromacy (“three-color vision”) -Normal Color Vision Anomalous Trichromacy (“unusual three-color vision”) -See all three primary colors. -One color is seen weakly -Protanomaly (L-cone defect) red-weak -Deuteranomaly (M-cone defect) green-weak -Tritanomaly (S-cone defect) blue-weak Dichromacy (“two-color vision”) -See only two of the three primary colors -One type of cone is totally absent or nonfunctional. -Protanopia (L-cone absent) -Deuteranopia (M-cone absent) -Tritanopia (S-cone absent) Rod Monochromacy (no cones at all) (“no-color vision”) -Sees no colors, only shades of gray.

8. 8 The Genetics of Color- Blindness How Color-Blind People See Things Defect in L-cone (poor red vision) Normal Defect in M-cone (poor green vision) Defect in S-cone (poor blue vision)

9. 9 The Genetics of Color- Blindness Human cells have 46 chromosomes, organized as 23 pairs.

10. 10 The Genetics of Color- Blindness X and Y: Our Sex Chromosomes Our 23 rd pair of chromosomes are our “sex chromosomes”, because they determine which sex we are. Females have two X chromosomes. Males have one X chromosome and one Y chromosome. -If you inherit a Y chromosome, you become a male. -The SRY gene on the Y chromosome controls your gender.

11. 11 The Genetics of Color- Blindness The X Chromosome and X-Linked Traits

12. 12 The Genetics of Color- Blindness Punnett Squares for X-linked Traits X R girl X R Y boy X R X r girl X r Y boy YXRXR Normal Jack XRXR XrXr Carrier Jill Color-blind boys get their trait from their carrier moms. X R X r girl X R Y boy X R X r girl X R Y boy YXrXr Color-Blind Jack XRXR XRXR Normal Jill Color-blind dads make ALL of their daughters carriers! “Carriers” exhibit the dominant trait (are unaffected) but carry the defective allele and can pass the trait on to their children.

13. 13 The Genetics of Color- Blindness Incidence of Color Vision Deficiencies ClassificationIncidence (%) Incidence (%) in Malesin Females Anomalous Trichromacy6.30.37 Protanomaly (L-cone defect)1.30.02 Deuteranomaly (M-cone defect)5.00.35 Tritanomaly (S-cone defect)0.00010.0001 Dichromacy2.40.03 Protanopia (L-cone absent)1.30.02 Deuteranopia (M-cone absent)1.20.01 Tritanopia (S-cone absent)0.0010.03 Rod Monochromacy (no cones) 0.00001 0.00001 Why are most kinds of color-blindness more common in men than women?

14. 14 The Genetics of Color- Blindness Punnett Squares for X-linked Traits: Why Color-Blindness is More Common in Males X R girl X R Y boy X R X r girl X r Y boy YXRXR Normal Jack XRXR XrXr Carrier Jill For a boy to be color-blind, he only needs to inherit ONE X r allele, from his carrier mom. X R X r girl X R Y boy X r girl X r Y boy YXrXr Color-Blind Jack XRXR XrXr Carrier Jill For a girl to be color- blind, she must inherit TWO X r alleles, one from her color-blind dad and one from her carrier mom.

15. 15 The Genetics of Color- Blindness Pedigrees are Genetic Family Trees males females normalaffected dadmom sondaughtersondaughter first bornlast born Boys are square? Girls are round? in order of birth

16. 16 The Genetics of Color- Blindness For traits that are controlled by genes on the 22 pairs of autosomes (non-sex chromosomes) Genotypes and Phenotypes for Recessive Traits A_ AA or Aa aa males females A_ AA or Aa aa dominantrecessive XAYXAYXaYXaY males females X A X _ X A X A or X A X a XaXaXaXa dominantrecessive For traits that are controlled by genes on the X chromosome (X-linked traits) “Carriers” exhibit the dominant trait (are unaffected) but carry the defective allele and can pass the trait on to their children! carrier

17. 17 The Genetics of Color- Blindness Professor Hershberger’s Rules for Interpreting Pedigrees Step 1: Match a genotype to each phenotype. -If the individual exhibits the recessive phenotype, he/she is aa (or X a X a for an X-linked trait) -If the individual exhibits the dominant phenotype, he/she is A_ (or X A _ for an X-linked trait). Step 2: Where possible, track alleles (genes) UP the pedigree, from child to parent. -Because children get one allele from each parent. Step 3: Where possible, track alleles (genes) DOWN the pedigree, from parent to child. -Because each parent gives one of his/her alleles to each child.

18. 18 The Genetics of Color- Blindness You are the Genetic Counselor. Gretchen is a carrier for red-green color- blindness. How will Gretchen’s choice of husband affect whether her children will be color-blind?

19. 19 The Genetics of Color- Blindness You are the Genetic Counselor! What if Gretchen marries a man who has normal vision? non- carrier Gretchen Gretchen’s Children Pam Rick girlboy girlboy 22 Possible Son-in-Law Gretchen 33 33 2 2 1: Label the pedigree chart with the genotypes of Rick, Pam, Gretchen, the “son- in-law”, and Gretchen’s possible children. 2: Enter Gretchen’s and her possible mate’s alleles into the Punnett Square above. 3: Determine the possible genotypes of their children from the Punnett Square. 4: Enter the probabilities for each of Gretchen’s possible children onto the pedigree chart. The “Son- in Law” 11 11 1 4 1 4 1 4 1 4 genotypes probabilities non- carrier 1 4

20. 20 The Genetics of Color- Blindness You are the Genetic Counselor! What if Gretchen marries a man who is color-blind? non- carrier Gretchen Gretchen’s Children Pam Rick girlboy girlboy 22 Possible Son-in-Law Gretchen 33 33 2 2 1: Label the pedigree chart with the genotypes of Rick, Pam, Gretchen, the “son- in-law”, and Gretchen’s possible children. 2: Enter Gretchen’s and her possible mate’s alleles into the Punnett Square above. 3: Determine the possible genotypes of their children from the Punnett Square. 4: Enter the probabilities for each of Gretchen’s possible children onto the pedigree chart. The “Son- in Law” 11 11 1 4 1 4 1 4 1 4 genotypes probabilities non- carrier 1 4

21. 21 The Genetics of Color- Blindness The Answers What happens if Gretchen marries a man who has normal vision?

22. 22 The Genetics of Color- Blindness non- carrier 11 11 Y ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? carrier Gretchen Pam Rick Possible Son-in-Law 1: Label the pedigree chart with the genotypes of Rick, Pam, Gretchen, the “son- in-law”, and Gretchen’s possible children. 2: Enter Gretchen’s and her possible mate’s alleles into the Punnett Square above. 3: Determine the possible genotypes of their children from the Punnett Square. 4: Enter the probabilities for each of Gretchen’s possible children onto the pedigree chart. The “Son- in Law” XrYXrY genotypes probabilities non- carrier girlboy girlboy 22 Gretchen 33 33 2 2 1 4 1 4 1 4 1 4 1 4 Using Prof. H’s Step #1: Because Rick is a male, he has a Y. Using Prof. H’s Step #1: Because he is color- blind, he has the mutant X r allele.

23. 23 The Genetics of Color- Blindness non- carrier 1 11 XXXRXXRX ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? carrier Gretchen Pam Rick Possible Son-in-Law 1: Label the pedigree chart with the genotypes of Rick, Pam, Gretchen, the “son- in-law”, and Gretchen’s possible children. 2: Enter Gretchen’s and her possible mate’s alleles into the Punnett Square above. 3: Determine the possible genotypes of their children from the Punnett Square. 4: Enter the probabilities for each of Gretchen’s possible children onto the pedigree chart. The “Son- in Law” XRXRXRXR genotypes probabilities non- carrier Using Prof. H’s Step #1: Because Pam is a female, she has two Xs. girlboy girlboy 22 Gretchen 33 33 2 2 1 4 1 4 1 4 1 4 1 4 XrYXrY Using Prof. H’s Step #1: Because she is NOT color- blind, she must have at least one dominant normal X R allele. Using Prof. H’s Step #3: Because Pam’s father and grandfather are not color-blind, and none of her brothers or nephews are, it’s likely that the X r allele does not appear in her pedigree. We can assume she did not inherit the X r allele and is thus NOT a carrier.

24. 24 The Genetics of Color- Blindness non- carrier 11 ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? carrier Gretchen Pam Rick Possible Son-in-Law 1: Label the pedigree chart with the genotypes of Rick, Pam, Gretchen, the “son- in-law”, and Gretchen’s possible children. 2: Enter Gretchen’s and her possible mate’s alleles into the Punnett Square above. 3: Determine the possible genotypes of their children from the Punnett Square. 4: Enter the probabilities for each of Gretchen’s possible children onto the pedigree chart. The “Son- in Law” genotypes probabilities non- carrier girlboy girlboy 22 Gretchen 33 33 2 2 1 4 1 4 1 4 1 4 1 4 XXXRXXRXXRXrXRXr Using Prof. H’s Step #2: To be a female, she had to inherit an X chromosome from her father. Her father’s only X chromosome carries the X r allele. Therefore, she must have inherited her father’s X r allele, and is thus a carrier. Using Prof. H’s Step #1: Because she is NOT color- blind, she must have at least one dominant normal X R allele. XrYXrYXRXRXRXR Using Prof. H’s Step #1: Because Gretchen is a female, she has two Xs.

25. 25 The Genetics of Color- Blindness non- carrier 11 ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? carrier Gretchen Pam Rick Possible Son-in-Law 1: Label the pedigree chart with the genotypes of Rick, Pam, Gretchen, the “son- in-law”, and Gretchen’s possible children. 2: Enter Gretchen’s and her possible mate’s alleles into the Punnett Square above. 3: Determine the possible genotypes of their children from the Punnett Square. 4: Enter the probabilities for each of Gretchen’s possible children onto the pedigree chart. The “Son- in Law” genotypes probabilities non- carrier girlboy girlboy 22 Gretchen 33 33 2 2 1 4 1 4 1 4 1 4 1 4 XXXRXXRXXRXrXRXr XrYXrYXRXRXRXR YXRYXRY Using Prof. H’s Step #1: Because the “Son- in-Law” is a male, he has a Y. Using Prof. H’s Step #1: Because he is NOT color-blind, he must have a normal X R allele.

26. 26 The Genetics of Color- Blindness 11111 XY XX non- carrier 11 ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? carrier Gretchen Pam Rick Possible Son-in-Law 1: Label the pedigree chart with the genotypes of Rick, Pam, Gretchen, the “son- in-law”, and Gretchen’s possible children. 2: Enter Gretchen’s and her possible mate’s alleles into the Punnett Square above. 3: Determine the possible genotypes of their children from the Punnett Square. 4: Enter the probabilities for each of Gretchen’s possible children onto the pedigree chart. The “Son- in Law” genotypes probabilities non- carrier girlboy girlboy 22 Gretchen 33 33 2 2 44444 XXXRXXRXXRXrXRXr XrYXrYXRXRXRXR YXRYXRY XRXXRXXRXXRXXrXrXrXr Using Prof. H’s Step #1: Males are XY. Females are XX. Using Prof. H’s Step #3: Daughters get Dad’s X chromosome, so all daughters will inherit a normal X R allele and have normal color vision. Using Prof. H’s Step #3: Sons get Dad’s Y chromosome. 0% no Using Prof. H’s Step #3: If Gretchen marries a man with normal color vision, they will NOT have any color-blind daughters, since all daughters will inherit their dad’s normal X R allele.

27. 27 The Genetics of Color- Blindness XY XRXXRXXRXXRX 1 XrYXrYXRYXRYXX non- carrier 11 ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? carrier Gretchen Pam Rick Possible Son-in-Law 1: Label the pedigree chart with the genotypes of Rick, Pam, Gretchen, the “son- in-law”, and Gretchen’s possible children. 2: Enter Gretchen’s and her possible mate’s alleles into the Punnett Square above. 3: Determine the possible genotypes of their children from the Punnett Square. 4: Enter the probabilities for each of Gretchen’s possible children onto the pedigree chart. The “Son- in Law” genotypes probabilities non- carrier girlboy girlboy 22 Gretchen 33 33 2 2 44444 XXXRXXRXXRXrXRXr XrYXrYXRXRXRXR YXRYXRY XRXRXRXR XRXrXRXr XrXrXrXr 0% Using Prof. H’s Step #3: The probability that any son will be color-blind will be determined by their odds of inheriting the X R or X r allele from Gretchen. Using Prof. H’s Step #3: The probability that any daughter will be a carrier will be determined by their odds of inheriting the X R or X r allele from Gretchen.

28. 28 The Genetics of Color- Blindness XY XRXXRXXRXXRX 1 XrYXrYXRYXRYXX non- carrier 11 ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? carrier Gretchen Pam Rick Possible Son-in-Law 1: Label the pedigree chart with the genotypes of Rick, Pam, Gretchen, the “son- in-law”, and Gretchen’s possible children. 2: Enter Gretchen’s and her possible mate’s alleles into the Punnett Square above. 3: Determine the possible genotypes of their children from the Punnett Square. 4: Enter the probabilities for each of Gretchen’s possible children onto the pedigree chart. The “Son- in Law” genotypes probabilities non- carrier girlboy girlboy 22 Gretchen 33 33 2 2 44444 XXXRXXRXXRXrXRXr XrYXrYXRXRXRXR YXRYXRY XRXRXRXR XRXrXRXr XrXrXrXr 0% YXRXR XRXR XrXr A Punnett Square is used to calculate the probabilities of various possible offspring. One parent’s alleles are used as row headings. These represent the genotypes of the gametes formed by that parent. In this case, these are Gretchen’s possible egg cells. The other parent’s alleles are used as column headings. These represent the genotypes of the gametes formed by that parent. In this case, these are the Son-in-Law’s possible sperm cells.

29. 29 The Genetics of Color- Blindness XY XRXXRXXRXXRX 1 XrYXrYXRYXRYXX non- carrier 11 ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? carrier Gretchen Pam Rick Possible Son-in-Law 1: Label the pedigree chart with the genotypes of Rick, Pam, Gretchen, the “son- in-law”, and Gretchen’s possible children. 2: Enter Gretchen’s and her possible mate’s alleles into the Punnett Square above. 3: Determine the possible genotypes of their children from the Punnett Square. 4: Enter the probabilities for each of Gretchen’s possible children onto the pedigree chart. The “Son- in Law” genotypes probabilities non- carrier girlboy girlboy 22 Gretchen 33 33 2 2 44444 XXXRXXRXXRXrXRXr XrYXrYXRXRXRXR YXRYXRY XRXRXRXR XRXrXRXr XrXrXrXr 0% YXRXR XRXR XrXr YXRXR YXRXR Carry the one parent’s alleles down within each column. Carry the other parent’s alleles across within each row. XRYXRYXRXRXRXR XrYXrYXRXrXRXr

30. 30 The Genetics of Color- Blindness XY XRXXRXXRXXRX 1 XrYXrYXRYXRYXX non- carrier 11 ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? carrier Gretchen Pam Rick Possible Son-in-Law 1: Label the pedigree chart with the genotypes of Rick, Pam, Gretchen, the “son- in-law”, and Gretchen’s possible children. 2: Enter Gretchen’s and her possible mate’s alleles into the Punnett Square above. 3: Determine the possible genotypes of their children from the Punnett Square. 4: Enter the probabilities for each of Gretchen’s possible children onto the pedigree chart. The “Son- in Law” genotypes probabilities non- carrier girlboy girlboy 22 Gretchen 33 33 2 2 44444 XXXRXXRXXRXrXRXr XrYXrYXRXRXRXR YXRYXRY XRXRXRXR XRXrXRXr XrXrXrXr 0% YXRXR XRXR XrXr YXRXR YXRXR XRYXRYXRXRXRXR XrYXrYXRXrXRXr 25% If Gretchen marries a man with normal color- vision, each of their children will have a 25% chance of being either a male with normal color vision a male with color-blindness a female non-carrier a female carrier

31. 31 The Genetics of Color- Blindness XY XRXXRXXRXXRX 1 XrYXrYXRYXRYXX non- carrier 11 ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? carrier Gretchen Pam Rick Possible Son-in-Law The “Son- in Law” genotypes probabilities non- carrier girlboy girlboy 22 Gretchen 33 33 2 2 44444 XXXRXXRXXRXrXRXr XrYXrYXRXRXRXR YXRYXRY XRXRXRXR XRXrXRXr XrXrXrXr 0% YXRXR XRXR XrXr YXRXR YXRXR XRYXRYXRXRXRXR XrYXrYXRXrXRXr 25% If Gretchen marries a man with normal color-vision, half of their sons will be color-blind, none of their daughters will be color-blind, half of their daughters will be carriers.

32. 32 The Genetics of Color- Blindness The Answers What happens if Gretchen marries a man who is red-green color-blind?

33. 33 The Genetics of Color- Blindness XY XRXXRXXRXXRX 1 XrYXrYXRYXRYXX non- carrier 11 ANSWER: Here’s what happens if Gretchen marries a man who is red-green color-blind? carrier Gretchen Pam Rick Possible Son-in-Law The “Son- in Law” genotypes probabilities non- carrier girlboy girlboy 22 Gretchen 33 33 2 2 44444 XXXRXXRXXRXrXRXr XrYXrYXRXRXRXR YXrYXrY XRXRXRXR XRXrXRXr XrXrXrXr 25% YXrXr XRXR XrXr YXRXR YXRXR XRYXRYXRXrXRXr XrYXrYXrXrXrXr 0% If Gretchen marries a man with red-green color-blindness, half of their sons will be color-blind, half of their daughters will be color-blind, the other half of their daughters will be carriers.

34. 34 The Genetics of Color- Blindness How will Gretchen’s choice of husband affect whether her children will be color-blind?

35. 35 The Genetics of Color- Blindness How will Gretchen’s choice of husband affect whether her children will be color-blind? Color-Blind Son-in-Law girlboy girlboy 2 Gretchen Y XrXr XRXR XrXr XRYXRYXRXrXRXr XrYXrYXrXrXrXr If Gretchen marries a man with red-green color-blindness, half of their sons will be color-blind, half of their daughters will be color- blind, half of their daughters will be carriers. Normal Son-in-Law girlboy girlboy 2 Gretchen Y XRXR XRXR XrXr XRYXRYXRXRXRXR XrYXrYXRXrXRXr If Gretchen marries a man with normal color-vision, half of their sons will be color-blind, none of their daughters will be color- blind, half of their daughters will be carriers.