Coaching Centre
Sex linkage and pedigrees
How sex is inherited, X-linked inheritance including red–green colour blindness and haemophilia, how to draw and read pedigree charts, and how to decide whether a trait is autosomal or X-linked, dominant or recessive.
About 1 in 12 boys of northern European descent can't easily tell red from green, but only about 1 in 200 girls. Same genes, same families, very different odds. The reason is that the gene sits on the X chromosome, and boys have only one.
Inheriting sex
A mother's eggs all carry an X chromosome. A father's sperm carry either an X or a Y, in roughly equal numbers. So the sperm decides the baby's chromosomal sex, and each pregnancy has about a 50% chance of XX and 50% of XY. A Punnett square of XX × XY gives XX, XX, XY, XY.
The X chromosome is large, with about 800 protein-coding genes, most of them nothing to do with sex: genes for colour vision, blood clotting and muscle proteins among them. The Y is small, with fewer than 100 genes, mostly involved in making sperm. Because females have two X chromosomes, one X in each of their body cells is switched off early in development (randomly chosen in each cell) so that males and females make similar amounts of X-gene products. Tortoiseshell cats show this: the fur colour gene is on the X, and patches of orange and black show which X is switched off in each patch of skin. That is why almost all tortoiseshell cats are female.
X-linked inheritance
Genes on the X chromosome are X-linked (or sex-linked). We write the alleles as superscripts on the X: for colour vision, Xᴮ (normal, dominant) and Xᵇ (colour blind, recessive).
| Genotype | Phenotype |
|---|---|
| XᴮXᴮ | female, normal vision |
| XᴮXᵇ | female, normal vision, carrier |
| XᵇXᵇ | female, colour blind |
| XᴮY | male, normal vision |
| XᵇY | male, colour blind |
A male has only one X, so whatever allele it carries shows. He cannot be a carrier: he either has the trait or he doesn't. A female needs two copies of a recessive X-linked allele to show it. So recessive X-linked traits are much more common in males. If a fraction q of X chromosomes carry the allele, about q of males are affected but only about q² of females: 8% of males (0.08) but 0.08² ≈ 0.6% of females, close to what is observed for red–green colour blindness.
A woman who is a carrier for colour blindness has children with a man with normal vision. What are the chances for their sons and daughters?
Mother XᴮXᵇ: eggs Xᴮ or Xᵇ. Father XᴮY: sperm Xᴮ or Y.
| Xᴮ | Xᵇ | |
|---|---|---|
| Xᴮ | XᴮXᴮ normal girl | XᴮXᵇ carrier girl |
| Y | XᴮY normal boy | XᵇY colour-blind boy |
Each son has a 50% chance of being colour blind. No daughter will be colour blind, but each has a 50% chance of being a carrier.
Notice two rules that come from where the X goes. A father passes his X to all his daughters and his Y to all his sons, so X-linked traits are never passed from father to son. And an affected male's daughters will all receive his allele.
Haemophilia A is another X-linked recessive condition. A missing clotting protein (factor VIII) means blood clots slowly, so injuries and internal bleeding can be dangerous. It affects about 1 in 5000 males. Queen Victoria was a carrier, and through her daughters it passed into the royal families of Spain, Germany and Russia, where her great-grandson Alexei, heir to the Russian throne, had the disease. Today people with haemophilia inject the missing clotting factor, and gene therapies that let the liver make it have been approved in several countries since 2022.
Pedigree charts
Geneticists can't set up crosses between people, so they study families. A pedigree is a family tree showing who has a trait, using standard symbols:
- square = male, circle = female
- shaded = has the trait (affected); unshaded = unaffected
- a dot in the middle, or half shading, sometimes shows a known carrier
- a horizontal line joins parents; a vertical line drops to a line joining their children (siblings), drawn left to right in birth order
- generations are numbered with Roman numerals (I, II, III) and individuals with numbers, so II-3 is the third person in generation II.
Reading a pedigree
Work through these questions in order.
- Dominant or recessive? If two unaffected parents have an affected child, the trait must be recessive (both parents are hidden carriers). If two affected parents have an unaffected child, it must be dominant (both parents are heterozygous). A dominant trait usually appears in every generation; a recessive one often skips generations.
- Autosomal or X-linked? Look at fathers and sons, and fathers and daughters.
- An affected father with an affected son rules out X-linked (sons get their father's Y).
- For X-linked recessive: an affected daughter must have an affected father, and an affected mother must have all affected sons. Mostly males are affected.
- For X-linked dominant: an affected father passes it to all his daughters and none of his sons.
- If nothing rules a pattern out, say which is most likely. Small families can fit more than one pattern.
- Work through all five families. For each, first decide dominant or recessive, then autosomal or X-linked.
- In family 1, which two people prove the trait is recessive? Which person rules out X-linked recessive?
- Find the family where an affected father has only affected daughters. What does that tell you?
- In family 3, write the genotype of every female. Which ones must be carriers?
Test yourself
Which parent determines whether a baby is chromosomally male or female?
Every egg has an X; sperm carry X or Y.
A colour-blind man (XᵇY) and a woman with genotype XᴮXᴮ have a daughter. She will be
She gets Xᵇ from her father and Xᴮ from her mother.
In a pedigree, two unaffected parents have an affected daughter. The trait is most likely
Recessive (unaffected parents); not X-linked recessive, because her father would have to be affected.
Which observation rules out X-linked inheritance?
Fathers pass a Y, not an X, to their sons.
A carrier woman (XᴴXʰ) and an unaffected man (XᴴY) have a son. The chance he has haemophilia is
Sons receive Xᴴ or Xʰ from their mother with equal chance.
Label the pedigree.
What does each observation tell you?
Genes carried on the X chromosome are said to be . A female with one recessive allele for colour blindness is a . In a pedigree, a represents a male. Haemophilia is caused by a missing factor. X-linked recessive traits are more common in .
Explain why red–green colour blindness is much more common in males than females, and why a colour-blind man cannot pass it to his sons. Use genotypes in your answer.
The colour vision gene is on the X chromosome and the colour-blind allele (Xᵇ) is recessive. A male is XY, so he has only one copy of the gene: if his X carries Xᵇ (XᵇY) he is colour blind, because there is no second X to carry a dominant Xᴮ. A female has two X chromosomes and is only colour blind if both carry the recessive allele (XᵇXᵇ); a female with XᴮXᵇ has normal vision and is a carrier. Since needing two copies is much less likely than needing one, many more males are affected: if 8% of X chromosomes carry Xᵇ, about 8% of males but only about 0.6% of females are colour blind. A father gives his X chromosome only to his daughters and his Y to his sons, so a colour-blind man's sons get their X from their mother and cannot inherit his Xᵇ. All his daughters, however, will be at least carriers.