Sex-linked inheritance and pedigree analysis
Recessive genes on the X chromosome, like those for haemophilia and colour blindness, show up mostly in males. A pedigree chart traces such traits through a family.
Why X-linked recessive traits are common in males
The X chromosome carries many genes that the Y does not. A male has only one X, so a recessive allele on it always shows. A female has two X chromosomes, so one normal X hides a faulty one; she is a carrier. A son always gets his X from his mother. So a carrier mother can pass the trait to her sons. A daughter is affected only if her father is affected and her mother is at least a carrier. That is why haemophilia is very rare in females. Queen Victoria was a carrier, and many of her descendants had haemophilia. For colour blindness, your textbook gives about 8% of males but only 0.4% of females.
Haemophilia: carrier mother and normal father
A woman whose father had haemophilia marries a man with normal blood clotting. What is the chance that (a) a son and (b) a daughter will have haemophilia? (Xʰ = X with the haemophilia allele.)
- The woman got her father's Xʰ, so she is a carrier: XXʰ.
- The man is normal: XY.
- Mother's eggs: X and Xʰ. Father's sperm: X and Y.
- Daughters: XX (normal) and XXʰ (carrier). None is affected.
- Sons: XY (normal) and XʰY (haemophilic), half each.
(a) 1 in 2 sons (50%) will have haemophilia. (b) No daughter will be haemophilic, but half will be carriers.
Colour blindness across three generations
A colour-blind man marries a woman with normal vision who is not a carrier. One of their daughters marries a man with normal vision. Work out their children and the daughter's sons. (Xᶜ = X with the colour blindness allele.)
- Man XᶜY × woman XX.
- All daughters are XXᶜ: normal vision, but carriers.
- All sons are XY: normal, because sons get the Y from their father.
- Carrier daughter XXᶜ × normal man XY.
- Her sons are XY (normal) or XᶜY (colour blind) in the ratio 1 : 1.
None of the man's children is colour blind, but all his daughters are carriers. Half of his daughter's sons will be colour blind: the trait passes from grandfather to grandson through a daughter (criss-cross inheritance).
Symbols used in pedigree charts
| Symbol | Meaning |
|---|---|
| Square | Male |
| Circle | Female |
| Diamond | Sex not specified |
| Filled (shaded) square or circle | Affected individual |
| Dot in the centre of a symbol (used in some charts) | Carrier |
| Horizontal line joining a male and a female | Mating |
| Double horizontal line | Mating between relatives (consanguineous mating) |
| Vertical line to a horizontal sibling line | Their children, eldest on the left |
| Number written inside a symbol | That many unaffected children, e.g. 5 |
| Roman numerals I, II, III on the left | Generations |
Reading a pedigree: deciding the pattern
- Trait in every generation, and every affected child has an affected parent: likely autosomal dominant (e.g. myotonic dystrophy).
- Trait skips a generation, and two unaffected parents have an affected child: recessive (e.g. sickle-cell anaemia, autosomal recessive).
- Mostly males affected, passed from an affected man through carrier daughters to grandsons, never father to son: X-linked recessive (haemophilia, colour blindness).
- An affected daughter with an unaffected father rules out X-linked recessive; the trait is autosomal.
- A double line (marriage between relatives) raises the chance of recessive disorders in the children.
Activity: spotting a pedigree chart of a family trait
Your practical exam may show a prepared pedigree chart for tongue rolling, ear lobes, widow's peak, blood groups or colour blindness.
- 1Number the generations I, II, III from the top, and the people in each from the left.
- 2Identify the symbols: males, females, affected (shaded), marriages and children.
- 3Note the trait. Practical manuals usually treat tongue rolling, free ear lobes and widow's peak as dominant. This is a simple classroom model; the real inheritance of these traits is more complex. Colour blindness is X-linked recessive; blood groups show multiple alleles.
- 4Check: does the trait appear in every generation (dominant) or skip one (recessive)? Are mostly males affected (X-linked)?
- 5Write the likely genotype of each person. Use a blank, such as T_, where one allele cannot be known.
- 6★Record: the pattern of inheritance, with one reason taken from the chart.
★ key step
Families with haemophilia in the pedigree can meet a genetic counsellor, who draws the family tree and explains the risk for each child. Patients are treated by giving them the missing clotting factor.
2 marks: “Why is haemophilia more common in males than in females?” The gene is X-linked recessive. A male has one X, so one faulty allele makes him affected. A female needs two faulty alleles: her father must be affected and her mother at least a carrier, which is very rare.
3 marks: “A colour-blind man marries a woman with normal vision whose father was colour blind. What are the chances of colour blindness in their sons and daughters?” Man XᶜY; woman XXᶜ (carrier). Daughters: XᶜXᶜ (colour blind) or XXᶜ (carrier), 50% colour blind. Sons: XY or XᶜY, 50% colour blind.
3 marks: “Draw any six symbols used in pedigree analysis and state what each means.” Square male, circle female, diamond sex unspecified, shaded affected, horizontal line mating, double line consanguineous mating, vertical line to offspring, number inside symbol for unaffected children.
X-linked recessive: mother carries, son suffers. Never passed from father to son.