The Genetics of Color-Blindness

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

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. The Genetics of Color-Blindness Anatomy of an Eyeball

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. The Genetics of Color-Blindness Photoreceptor Proteins

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

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

10. The Genetics of Color-Blindness X and Y: Our Sex Chromosomes • Our 23rd 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. The Genetics of Color-Blindness The X Chromosome and X-Linked Traits

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

13. The Genetics of Color-Blindness Why are most kinds of color-blindness more common in men than women? Incidence of Color Vision Deficiencies Classification Incidence (%) Incidence (%) in Males in Females Anomalous Trichromacy 6.3 0.37 Protanomaly (L-cone defect) 1.3 0.02 Deuteranomaly (M-cone defect) 5.0 0.35 Tritanomaly (S-cone defect) 0.0001 0.0001 Dichromacy 2.4 0.03 Protanopia (L-cone absent) 1.3 0.02 Deuteranopia (M-cone absent) 1.2 0.01 Tritanopia (S-cone absent) 0.001 0.03 Rod Monochromacy (no cones) 0.00001 0.00001

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

15. The Genetics of Color-Blindness Pedigrees are Genetic Family Trees Boys are square? Girls are round? normal affected males females dad mom son daughter son daughter first born last born in order of birth

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

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 XaXa for an X-linked trait) • If the individual exhibits the dominant phenotype, he/she is A_ (or XA_ 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. The Genetics of Color-Blindness You are theGenetic 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. The Genetics of Color-Blindness You are the Genetic Counselor!What if Gretchen marries a man who has normal vision? Possible Son-in-Law 1 1 non- carrier 2 2 Rick Pam Gretchen 3 3 2 The “Son-in Law” Gretchen 1 1 3 3 2 Gretchen’s Children non- carrier carrier 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. 1 1 1 1 1 genotypes 4 4 4 4 4 probabilities

20. The Genetics of Color-Blindness You are the Genetic Counselor!What if Gretchen marries a man who is color-blind? Possible Son-in-Law 1 1 non- carrier 2 2 Rick Pam Gretchen 3 3 2 The “Son-in Law” Gretchen 1 1 3 3 2 Gretchen’s Children non- carrier carrier 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. 1 1 1 1 1 genotypes 4 4 4 4 4 probabilities

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

22. The Genetics of Color-Blindness Using Prof. H’s Step #1: Because Rick is a male, he has a Y. ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? Possible Son-in-Law 1 XrY Y 1 non- carrier Using Prof. H’s Step #1: Because he is color-blind, he has the mutant Xr allele. 2 2 Rick Pam Gretchen 3 3 2 The “Son-in Law” Gretchen 1 1 3 3 2 non- carrier carrier 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. 1 1 1 1 1 genotypes 4 4 4 4 4 probabilities

23. The Genetics of Color-Blindness Using Prof. H’s Step #1: Because Pam is a female, she has two Xs. ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? Using Prof. H’s Step #1: Because she is NOT color-blind, she must have at least one dominant normal XR allele. Possible Son-in-Law XrY XRX XRXR 1 XX non- carrier 2 2 Rick Pam Gretchen 3 3 2 The “Son-in Law” Gretchen 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 Xr allele does not appear in her pedigree. We can assume she did not inherit the Xr allele and is thus NOT a carrier. 1 1 3 3 2 non- carrier carrier 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. 1 1 1 1 1 genotypes 4 4 4 4 4 probabilities

24. The Genetics of Color-Blindness Using Prof. H’s Step #1: Because Gretchen is a female, she has two Xs. ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? Possible Son-in-Law XrY XRXR non- carrier 2 2 Rick Pam Gretchen 3 3 2 The “Son-in Law” Gretchen 1 XX 1 XRX XRXr 3 3 2 Using Prof. H’s Step #1: Because she is NOT color-blind, she must have at least one dominant normal XR allele. non- carrier carrier 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. 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 Xr allele. Therefore, she must have inherited her father’s Xr allele, and is thus a carrier. 1 1 1 1 1 genotypes 4 4 4 4 4 probabilities

25. The Genetics of Color-Blindness ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? Possible Son-in-Law XrY XRXR non- carrier 2 2 Rick Pam Gretchen Using Prof. H’s Step #1: Because the “Son-in-Law” is a male, he has a Y. 3 3 2 The “Son-in Law” Gretchen Y XRY 1 XX XRXr XRX 1 3 3 2 Using Prof. H’s Step #1: Because he is NOT color-blind, he must have a normal XR allele. non- carrier carrier 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. 1 1 1 1 1 genotypes 4 4 4 4 4 probabilities

26. The Genetics of Color-Blindness ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? 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 XR allele. Possible Son-in-Law XrY XRXR non- carrier 2 2 Rick Pam Gretchen Using Prof. H’s Step #3: Daughters get Dad’s X chromosome, so all daughters will inherit a normal XR allele and have normal color vision. 3 3 2 The “Son-in Law” Gretchen 1 Y XRY XX 1 XRXr XRX 3 3 2 no Using Prof. H’s Step #3: Sons get Dad’s Y chromosome. non- carrier carrier 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. 1 XY 1 XRX XX XRX 1 XX 1 XY 1 XrXr XX genotypes Using Prof. H’s Step #1: Males are XY. Females are XX. 4 4 4 4 4 0% probabilities

27. The Genetics of Color-Blindness ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? Using Prof. H’s Step #3: The probability that any daughter will be a carrier will be determined by their odds of inheriting the XR or Xr allele from Gretchen. Possible Son-in-Law Using Prof. H’s Step #3: The probability that any son will be color-blind will be determined by their odds of inheriting the XR or Xr allele from Gretchen. XrY XRXR non- carrier 2 2 Rick Pam Gretchen 3 3 2 The “Son-in Law” Gretchen XRY Y 1 XX 1 XRXr XRX 3 3 2 non- carrier carrier 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. XRY XY XRXR XRX XRXr XRX XrY XY XX 1 XrXr genotypes 4 4 4 4 0% 4 probabilities

28. The Genetics of Color-Blindness 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. ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? Possible Son-in-Law XrY XRXR non- carrier XR 2 2 Y Rick Pam Gretchen 3 3 2 XR The “Son-in Law” Gretchen 1 Y XRY XRX XX 1 XRXr 3 3 2 Xr non- carrier carrier 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. 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. A Punnett Square is used to calculate the probabilities of various possible offspring. XRY XY XRX XRXR XRXr XRX XY XrY XrXr 1 XX genotypes 4 4 4 4 4 0% probabilities

29. The Genetics of Color-Blindness ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? Possible Son-in-Law Carry the one parent’s alleles down within each column. XrY XRXR non- carrier XR 2 Y 2 Rick Pam Gretchen XR 3 XRXR XRY 3 Y XR 2 The “Son-in Law” Gretchen 1 XRY Y XRX XX 1 XRXr XR XRXr 3 Y XrY 3 2 Xr non- carrier carrier 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. Carry the other parent’s alleles across within each row. XRY XY XRX XRXR XRX XRXr XrY XY XrXr XX 1 genotypes 4 4 4 4 4 0% probabilities

30. The Genetics of Color-Blindness ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? • 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 Possible Son-in-Law XrY XRXR non- carrier XR 2 Y 2 Rick Pam Gretchen XRXR 3 XR XRY 3 Y XR 2 The “Son-in Law” Gretchen Y XRY 1 XRXr XRX 1 XX 3 XR XRXr 3 Y XrY 2 Xr non- carrier carrier 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. XY XRY XRX XRXR XRX XRXr XrY XY XrXr XX 1 genotypes 25% 4 4 25% 25% 4 4 25% 4 0% probabilities

31. The Genetics of Color-Blindness ANSWER: Here’s what happens if Gretchen marries a man who has normal vision? Possible Son-in-Law XrY XRXR non- carrier XR 2 Y 2 Rick Pam Gretchen 3 XRXR XR 3 XRY Y 2 XR The “Son-in Law” Gretchen 1 Y XRY XRXr XRX 1 XX XR 3 XRXr XrY 3 Y Xr 2 non- carrier carrier • 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. XRY XY XRXR XRX XRXr XRX XrY XY XrXr XX 1 genotypes 25% 4 25% 4 4 25% 4 25% 0% 4 probabilities

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

33. The Genetics of Color-Blindness ANSWER: Here’s what happens if Gretchen marries a man who is red-green color-blind? Possible Son-in-Law XrY XRXR non- carrier Xr 2 Y 2 Rick Pam Gretchen 3 XRXr XR 3 XRY Y 2 XR The “Son-in Law” Gretchen 1 Y XrY XRXr XRX 1 XX XR 3 XrXr XrY 3 Y Xr 2 non- carrier carrier • 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. XRY XY XRXR XRX XRXr XRX XrY XY XrXr XX 1 genotypes 25% 4 0% 4 4 25% 4 25% 25% 4 probabilities

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

35. The Genetics of Color-Blindness How will Gretchen’s choice of husband affect whether her children will be color-blind? • 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. • 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 Color-Blind Son-in-Law 2 XR Y 2 Xr Y Gretchen Gretchen Gretchen XRXR XRY XRXr XRY XR XR XRXr XrY XrXr XrY Xr Xr