The Genetics of Color-Blindness Dr. Rick Hershberger • http://www.rickhershberger.com Rick Hershberger • 21 November 2018

Defects in Human Color Vision A Gene for Red-Green Color Blindness 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?

The Genetics of Color-Blindness Anatomy of an Eyeball

The Retina Contains Two Types of Light-Detecting Cells 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

Photoreceptor Proteins The Genetics of Color-Blindness Photoreceptor Proteins

How Color-Blind People See Things 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.

Types of Color Vision Deficiencies 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.

How Color-Blind People See Things 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)

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

X and Y: Our Sex Chromosomes 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.

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

Punnett Squares for X-linked Traits The Genetics of Color-Blindness Punnett Squares for X-linked Traits The Genetics of Color-Blindness 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. XRXR girl XRY boy XRXr XrY XRXr girl XRY boy XR XR Xr XR Color-blind boys get their trait from their carrier moms. Color-blind dads make ALL of their daughters carriers! Rick Hershberger • 21 November 2018

Incidence of Color Vision Deficiencies 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

XR Y Xr Y XR XR Xr Xr XRXR XRY XRXr XrY XRXr XRY XrXr XrY 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 XRXR girl XRY boy XRXr XrY XRXr girl XRY boy XrXr XrY 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.

Pedigrees are Genetic Family Trees 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 in order of birth last born

Genotypes and Phenotypes for Recessive Traits 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

Professor Hershberger’s Rules for Interpreting Pedigrees 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.

You are the Genetic Counselor. 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?

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 girl boy 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 probabilities 4 4 4 4 4

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 girl boy 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 probabilities 4 4 4 4 4

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

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 XrY 1 Y 1 non- carrier 2 Using Prof. H’s Step #1: Because he is color-blind, he has the mutant Xr allele. 2 Rick Pam Gretchen girl boy 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 probabilities 4 4 4 4 4

Because Pam is a female, she has two Xs. 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 XRXR XX 1 XRX non- carrier 2 2 Rick Pam Gretchen girl boy 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 probabilities 4 4 4 4 4

Because Gretchen is a female, she has two Xs. 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 girl boy 3 3 2 The “Son-in Law” Gretchen 1 1 XRX XRXr XX 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 probabilities 4 4 4 4 4

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. girl boy 3 3 2 The “Son-in Law” Gretchen Y 1 XRY XRXr 1 XRX XX 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 probabilities 4 4 4 4 4

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. girl boy 3 3 2 The “Son-in Law” Gretchen XRY 1 Y 1 XRXr XRX XX 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 XX XRX 1 XRX XX 1 XY 1 1 XX XrXr genotypes Using Prof. H’s Step #1: Males are XY. Females are XX. probabilities 4 4 4 4 4 0%

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. 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. Possible Son-in-Law XrY XRXR non- carrier 2 2 Rick Pam Gretchen girl boy 3 3 2 The “Son-in Law” Gretchen Y 1 XRY XRXr 1 XRX XX 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 XrXr XX 1 genotypes probabilities 4 4 4 4 4 0%

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

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 2 XR 2 Y Rick Pam Gretchen girl boy XRXR 3 XR XRY 3 Y XR 2 The “Son-in Law” Gretchen XRY Y 1 XX XRX XRXr 1 XR XRXr 3 Y XrY 3 Xr 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. Carry the other parent’s alleles across within each row. XY XRY XRX XRXR XRXr XRX XY XrY XX XrXr 1 genotypes probabilities 4 4 4 4 4 0%

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 2 XR Y 2 Rick Pam Gretchen girl boy XR XRXR 3 3 Y XRY XR 2 The “Son-in Law” Gretchen XRY Y 1 XRX XRXr XX 1 XR XRXr 3 Y XrY 3 Xr 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 XY XrY 1 XX XrXr genotypes probabilities 25% 4 25% 4 25% 4 25% 4 0% 4

If Gretchen marries a man with normal color-vision, 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 XR Y 2 Rick Pam Gretchen girl boy XRXR XR 3 3 XRY Y XR 2 The “Son-in Law” Gretchen Y XRY 1 XRX XX 1 XRXr 3 XR XRXr Y XrY 3 2 Xr 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. XY XRY XRX XRXR XRX XRXr XrY XY XrXr 1 XX genotypes probabilities 25% 4 25% 4 25% 4 25% 4 4 0%

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

If Gretchen marries a man with red-green color-blindness, 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 2 Xr Y 2 Rick Pam Gretchen girl boy XRXr XR 3 3 XRY Y XR 2 The “Son-in Law” Gretchen Y XrY 1 XRX XX 1 XRXr 3 XR XrXr Y XrY 3 2 Xr 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. XY XRY XRX XRXR XRX XRXr XrY XY XrXr 1 XX genotypes probabilities 25% 4 0% 4 25% 4 25% 4 4 25%

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

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 Xr 2 Y Gretchen Gretchen Gretchen girl boy girl boy XRXR XRY XRXr XRY XR XR XRXr XrY XrXr XrY Xr Xr