D. Genetic Processes · Genetic ProcessesSex-Linked Inheritance and Pedigrees
D3.3 D2.3 D2.1 D2.4 A2.2 A1.12About 75 minutes
Learning goals- I can explain why X-linked recessive traits are more common in males.
- I can use Xᴮ/Xᵇ/Y notation in Punnett squares for sex-linked crosses.
- I can read and draw a pedigree with the standard symbols.
- I can use a pedigree to decide whether a trait is dominant or recessive, and autosomal or X-linked.
Words to know
sex-linked (X-linked) gene
A gene located on the X chromosome; its inheritance pattern differs in males and females.
hemizygous
Having only one copy of a gene, as a typical XY male does for X-linked genes.
carrier
A heterozygous individual who carries a recessive allele but does not show the trait (for X-linked traits, usually a female XᴮXᵇ).
pedigree
A chart of a family's relationships over generations that shows who has a trait.
SRY gene
A gene on the Y chromosome that starts the development of testes in an embryo.
Barr body
The condensed, inactivated X chromosome seen in the nuclei of cells with two (or more) X chromosomes.
A trait that skips generations
About 1 in 12 men of Northern European ancestry has red-green colour vision deficiency (often called colour blindness), but only about 1 in 200 women. Why would a trait be so much more common in one sex? The answer is not about being male or female as such; it is about where the gene is: on the X chromosome.
Sex chromosomes and sex determination
In humans, most females have two X chromosomes (XX) and most males have one X and one Y (XY). Every egg carries an X. A sperm carries either an X or a Y, so the sperm determines the chromosomal sex of the child, with about a 1/2 chance of each.
The Y chromosome carries the SRY gene, which switches on the development of testes. The X chromosome is large and carries hundreds of genes for things that have nothing to do with sex: colour vision, a blood-clotting factor, muscle proteins and more. The Y has no matching copies of most of these.
So for X-linked genes:
- A typical female (XX) has two alleles, like any autosomal gene.
- A typical male (XY) has only one allele: he is hemizygous. Whatever allele is on his X shows, dominant or recessive.
Notation for X-linked crosses
Write the allele as a superscript on the X: Xᴮ (normal colour vision, dominant) and Xᵇ (red-green colour vision deficiency, recessive). The Y gets no allele. There are five possible genotypes:
| Genotype | Phenotype |
|---|
| XᴮXᴮ | female, normal vision |
| XᴮXᵇ | female, normal vision (carrier) |
| XᵇXᵇ | female, colour vision deficiency |
| XᴮY | male, normal vision |
| XᵇY | male, colour vision deficiency |
A male has the condition with just one recessive allele. A female needs two, one from each parent, which means her father must have the condition too. That is why X-linked recessive traits are far more common in males.
Worked exampleExample 1: An X-linked cross
Hemophilia A (a blood-clotting disorder) is X-linked recessive. A woman whose father had hemophilia, and who does not have it herself, has children with a man who does not have hemophilia.
(a) What is the woman's genotype? (b) What is the probability that their son has hemophilia? (c) What is the probability that a child (sex not known) has hemophilia?
- Key: Xᴴ = normal clotting, Xʰ = hemophilia.
- (a) Her father was XʰY and gave her his X, so she got Xʰ. She does not have hemophilia, so her other X is Xᴴ: she is XᴴXʰ, a carrier.
- The man is XᴴY. Punnett square: XᴴXᴴ, XᴴXʰ (daughters); XᴴY, XʰY (sons).
- (b) Given that the child is a son, he is XᴴY or XʰY: probability 1/2.
- (c) Of all four equally likely children, only XʰY has hemophilia: 1/4.
(a) XᴴXʰ (b) 1/2 (c) 1/4.
Read the question carefully
"The probability that a son has the condition" (1/2 here) is different from "the probability that a child is a son with the condition" (1/4). In the first, you already know the child is a boy; look only at the boy boxes.
Thomas Hunt Morgan's fruit flies
In 1910, at Columbia University, Thomas Hunt Morgan found a male fruit fly with white eyes instead of the normal red. Crossing it gave results that only made sense if the eye-colour gene was on the X chromosome: white eyes showed up mainly in males. This was some of the first strong evidence that genes are carried on chromosomes, and it earned Morgan a Nobel Prize in 1933.
A Canadian discovery: the Barr body
In 1949, at the University of Western Ontario in London, Ontario, Murray Barr and his student Ewart Bertram noticed a small dark spot in the nuclei of nerve cells from female cats, but not from males. This Barr body turned out to be an X chromosome that is switched off. In cells with two X chromosomes, one X in each cell is inactivated early in development, so females and males have similar amounts of X-gene activity.
Pedigrees
Geneticists and genetic counsellors cannot do test crosses on people, so they study pedigrees: family charts that show who has a trait.
- Square = male, circle = female.
- Filled = has the trait (affected); empty = does not.
- A horizontal line between a male and a female = they are parents together; a vertical line drops to their children, who hang from a horizontal sibship line in birth order (oldest on the left).
- Roman numerals number the generations; Arabic numbers number the people in each generation (II-4 = generation II, person 4).
| Pattern | Clues in the pedigree |
|---|
| Autosomal recessive | Affected children can have two unaffected parents (both carriers); skips generations; males and females affected about equally. |
| Autosomal dominant | Every affected person has at least one affected parent; does not skip generations; males and females about equally; two affected parents can have an unaffected child. |
| X-linked recessive | Mostly males affected; affected males usually have unaffected (carrier) mothers; never passed from father to son; an affected father passes the allele to all his daughters. |
Worked exampleExample 2: Analysing the pedigree above
Use the pedigree figure. (a) Why can't the trait be autosomal dominant? (b) What is the genotype of I-2? (c) What is the probability that III-2 is a carrier?
- (a) II-1 is affected but neither parent (I-1, I-2) is. A dominant trait would show in at least one parent, so the trait is recessive.
- Only males are affected and the affected males have unaffected mothers: consistent with X-linked recessive.
- (b) I-2 must have given Xᵃ to her affected son II-1 (sons get their X from their mother): she is XᴬXᵃ.
- (c) III-2's mother II-4 is a carrier (XᴬXᵃ, she has an affected son) and her father II-5 is XᴬY. A daughter gets Xᴬ from her father and either Xᴬ or Xᵃ from her mother: P(carrier) = 1/2.
(a) Two unaffected parents had an affected child, so it is recessive. (b) XᴬXᵃ. (c) 1/2.
Just for funAlmost every calico cat (patches of orange, black and white) is female. The orange and black fur-colour alleles are on the X chromosome, and a female's patches show which X was switched off in each region of skin. That's X-inactivation, the same thing Murray Barr spotted under his microscope, showing up on a cat.
Hands-on activityBuild a family-trait pedigree (with a made-up family)
You need: paper, a pencil and a ruler.
- Invent a three-generation family of 10 to 14 people (use names of fictional characters if you like). Use the standard symbols.
- Choose an X-linked recessive trait (for example, red-green colour vision deficiency). Start with a carrier grandmother. For each child, flip a coin to decide which X the mother passes on, and a second coin for the child's sex.
- Fill in who is affected. Mark each female who must be a carrier with a dot.
- Give your pedigree to a family member (without telling them the pattern). Can they work out that it is X-linked recessive using the clues table?
What to look for: affected males with unaffected mothers, no father-to-son passing, and fewer affected females. If you want a real-world check, free online colour-vision tests exist, but a diagnosis needs an eye-care professional.
Note: please keep this to an imaginary family. Real family health information is private.
Your turn
1Why are X-linked recessive traits more common in males than in females?
A male has only one X, so one recessive allele is enough to show the trait. A female needs the recessive allele on both X chromosomes.
2Give the genotype of (a) a carrier female, (b) a male with red-green colour vision deficiency.
3Can a father pass an X-linked trait to his son? Explain.
No. A father gives his son a Y, not an X. The son's X comes from his mother.
4A woman with normal vision whose father had red-green CVD has a son with a man with normal vision. What is the probability that the son has CVD?
She is XᴮXᵇ; the son gets Xᴮ or Xᵇ from her: 1/2.
5In a pedigree, what do a square, a circle and a filled shape mean?
Square = male; circle = female; filled = affected (has the trait).
6Two unaffected parents have an affected daughter. Is the trait dominant or recessive? Could it be X-linked recessive?
Recessive (unaffected parents, affected child). It is not X-linked recessive: an affected daughter would need an affected father (XᵃY), but her father is unaffected. So it is autosomal recessive.
More practice: warm-up
1What are the sex chromosomes of a typical human male?
2Which parent's gamete determines the chromosomal sex of a child?
The father's (sperm carries X or Y).
3What does hemizygous mean?
Having only one copy of a gene (like a male's X-linked genes).
4Who discovered white-eyed fruit flies and X-linked inheritance?
Thomas Hunt Morgan (1910).
5Write the genotype of a female with hemophilia.
More practice: on your own
1A man with hemophilia (XʰY) and a woman who is homozygous normal (XᴴXᴴ) have children. Describe their sons and daughters.
Sons get the mother's Xᴴ: all sons unaffected (XᴴY). Daughters get the father's Xʰ: all daughters are carriers (XᴴXʰ), unaffected.
2A woman with red-green CVD (XᵇXᵇ) has children with a man with normal vision. Predict their children.
Daughters XᴮXᵇ: normal vision, carriers. Sons XᵇY: all have CVD.
3In fruit flies, red eyes (Xᴿ) are dominant to white (Xʳ). A white-eyed female is crossed with a red-eyed male. What eye colours do the offspring have?
XʳXʳ × XᴿY: daughters XᴿXʳ (red eyes), sons XʳY (white eyes).
4A trait appears in every generation of a pedigree, affects males and females equally, and every affected person has an affected parent. What is the most likely pattern?
5Why is the Barr body important for X-linked genes?
In cells with two X chromosomes, one X is inactivated (the Barr body), so females and males end up with similar levels of X-gene activity.
Challenge
1A couple has a son with Duchenne muscular dystrophy (X-linked recessive). Neither parent has the condition. What is the probability that their next child is a son with the condition? A daughter who is a carrier?
The mother must be XᴰXᵈ (the father is XᴰY). Four equally likely children: XᴰXᴰ, XᴰXᵈ, XᴰY, XᵈY. Son with the condition: 1/4. Carrier daughter: 1/4.
2Combine genes: a woman who is a carrier for red-green CVD and has type A blood (Iᴬi) has children with a man with normal vision and type O blood. What is the probability that a child is a son with CVD and type O blood?
CVD part: P(XᵇY) = 1/4 (from XᴮXᵇ × XᴮY). Blood: Iᴬi × ii gives P(type O) = 1/2. Independent genes (X chromosome and chromosome 9): 1/4 × 1/2 = 1/8.
3Can a female have an X-linked recessive condition? Describe the parents needed, and explain why this is rare.
Yes: she needs Xᵃ from both parents, so her father must be affected (XᵃY) and her mother must be a carrier or affected. This is rare because it needs an affected father and a mother carrying a rare allele; if the allele frequency is q, about q² females are affected versus q males.
Quiz
1. A man has an X-linked recessive condition. Which of his children will inherit the allele?
2. What is the genotype of a carrier female for red-green colour vision deficiency?
3. A carrier female (XᴴXʰ) and a normal male (XᴴY) have a son. The probability that he has hemophilia is:
4. In a pedigree, a filled square represents:
5. Which pedigree pattern rules out X-linked recessive inheritance?
6. Thomas Hunt Morgan's work with white-eyed fruit flies provided evidence that:
Big idea: This lesson covers sex linkage (D3.3) and sex-linked Punnett squares (D2.3), with pedigree analysis as a way of working out genotypes (D2.4).
How to help: Keep the pedigree work to imaginary families. Real family health histories are private, and some families include adoption, donor conception or step-relationships. If your teen is curious about a condition in your own family, a family doctor or genetic counsellor is the right source.
Language note: The lesson uses "most females are XX and most males are XY" because some people have other sex-chromosome combinations (covered in the chromosomal disorders lesson) and biological sex is not the same as gender identity. Keep discussion respectful.
Common difficulties:
- Giving the Y an allele.
- Mixing up "probability a son is affected" (1/2) and "probability a child is an affected son" (1/4).
- Forgetting that sons always get their X from their mother.