Sex Linkage

Not all genes are inherited equally. Those on the sex chromosomes show distinctive inheritance patterns because males and females carry different combinations of sex chromosomes. Sex-linked inheritance is particularly important because several well-known human genetic disorders, including haemophilia, red-green colour blindness and Duchenne muscular dystrophy, are X-linked recessive conditions that affect males much more frequently than females. OCR A-Level Biology A specification module 6.1.2(c) requires you to understand sex linkage and be able to analyse sex-linked pedigrees and crosses.

Key Definitions:

• Sex linkage — the inheritance of a gene carried on a sex chromosome.
• X-linked — carried on the X chromosome.
• Y-linked — carried on the Y chromosome.
• Autosome — any chromosome that is not a sex chromosome.
• Carrier (heterozygote) — a female heterozygous for a recessive X-linked allele who does not usually show the trait but can pass it on.
• Hemizygous — having only one copy of a gene (e.g. males for all X-linked genes).

---

Sex Determination in Humans

Humans have 23 pairs of chromosomes: 22 pairs of autosomes and one pair of sex chromosomes (the 23rd pair).

• Females are XX — two X chromosomes.
• Males are XY — one X and one Y.

The Y chromosome is much smaller than the X and carries fewer than 100 genes. The X chromosome carries over 800. Therefore:

• A female has two copies of every X-linked gene — she can be homozygous or heterozygous.
• A male has only one copy of every X-linked gene (hemizygous), so whatever allele he carries on his single X will be expressed. There is no "carrier" state for males.

Men pass their X to daughters and their Y to sons. Women pass one of their two Xs to every child regardless of sex. This asymmetry produces the characteristic sex-linked inheritance pattern.

---

X-Linked Recessive Inheritance

Most sex-linked diseases are X-linked recessive. A male with the allele is affected; a female needs two copies to be affected, and a female with one copy is a carrier (usually unaffected but able to pass it on).

Key observations about X-linked recessive conditions

• Affected males far outnumber affected females.
• A carrier mother has a 50% chance of passing the allele to each child. Half her sons will be affected; half her daughters will be carriers.
• An affected father passes his X (with the allele) to every daughter (all become carriers) and his Y (no allele) to every son (all unaffected, unless they inherit it from their mother).
• Affected individuals often "skip" generations, appearing in grandsons via unaffected carrier daughters.

Punnett square: carrier mother × unaffected father

Let Xᴬ be the normal allele and Xᵃ the recessive disease allele.

	Xᴬ	Y
Xᴬ	XᴬXᴬ	XᴬY
Xᵃ	XᴬXᵃ	XᵃY

Offspring: 1 unaffected daughter : 1 carrier daughter : 1 unaffected son : 1 affected son. Among sons alone, half are affected. Among daughters alone, half are carriers.

Punnett square: affected father × unaffected non-carrier mother

	Xᴬ	Xᴬ
Xᵃ	XᴬXᵃ	XᴬXᵃ
Y	XᴬY	XᴬY

All daughters are carriers; all sons are unaffected.

---

Named Examples

1. Haemophilia A

• Caused by a recessive allele on the X chromosome in the gene for clotting factor VIII.
• Affected males bleed excessively from minor injuries and suffer from internal joint bleeding.
• The "royal haemophilia" that spread through European royal families from Queen Victoria is the most famous historical example — Victoria was a carrier and passed the allele to several of her descendants.
• Incidence: around 1 in 5,000 males. Affected females are extraordinarily rare.

2. Red-Green Colour Blindness

• Caused by recessive alleles on the X chromosome in the genes for red or green photopigments in the cone cells of the retina.
• Affected individuals cannot distinguish red from green.
• Affects around 8% of males and only ~0.5% of females of European ancestry — the most common X-linked condition.

3. Duchenne Muscular Dystrophy (DMD)