AQA A-Level Biology: Sex Linkage, Autosomal Linkage and Epistasis

The tidy ratios of a dihybrid cross assume that genes are inherited independently. Often they are not. This guide explains three situations that change the pattern of inheritance: sex linkage, where a gene sits on a sex chromosome; autosomal linkage, where two genes travel together on the same chromosome; and epistasis, where one gene overrides another. Each explains why real offspring ratios can depart from the ones you would predict.

Sex linkage

A sex-linked gene is one whose locus is on a sex chromosome, normally the X chromosome. This matters because the two sexes carry different sex chromosomes.

In humans, females are XX and males are XY. The Y chromosome is much shorter than the X and carries few genes, so for a gene on the X chromosome:

• Females (XX) have two alleles. A female only shows a recessive X-linked condition if she is homozygous recessive; with one recessive allele she is an unaffected carrier.
• Males (XY) have only one allele of the gene, inherited on the single X chromosome from their mother. There is no second allele on the Y to mask it, so a recessive allele is always expressed in a male.

This is why recessive X-linked conditions, such as red-green colour blindness and haemophilia, are far more common in males. Pedigree diagrams can reveal sex linkage: if a condition appears mainly in males, it suggests the gene is on the X chromosome, and an unaffected mother with an affected child must be a carrier. You can also rule sex linkage out. If an affected father has an unaffected daughter, the gene cannot be a recessive one on the X chromosome, because he would have passed his only X-linked allele to her and she would be affected or a carrier accordingly.

(In some organisms, such as birds, the system is reversed, with males XX and females XY. The same reasoning then applies with the sexes swapped.)

Autosomal linkage

Autosomal linkage is when two genes lie on the same autosome, a chromosome that is not a sex chromosome. Because the genes are on the same chromosome, their alleles travel together into a gamete rather than being sorted independently.

• During meiosis, the two linked alleles stay together through the independent segregation of homologous chromosomes, so they are usually inherited as a unit.
• The exception is crossing over, which can swap sections between homologous chromosomes and produce new combinations of the linked alleles.
• The closer together two genes are on the chromosome, the less likely crossing over is to separate them, so the more tightly they are inherited together.

Autosomal linkage means a dihybrid cross does not give the expected 9 : 3 : 3 : 1 ratio. Instead, the parental combinations of alleles appear far more often than expected, with only a small number of recombinant offspring produced by crossing over.

Epistasis

Epistasis is the interaction of two non-linked genes where one gene masks or suppresses the expression of the other. In other words, whether the second gene shows up at all depends on the alleles present at the first.

A common example is a gene that controls whether a pigment is produced at all, and a second gene that controls the colour of that pigment. If the first gene prevents any pigment being made, the alleles of the second gene make no difference to the phenotype, because there is no pigment for them to colour. Because one gene overrides the other, epistasis also distorts the expected offspring ratios of a dihybrid cross.

How this fits together

Sex linkage, autosomal linkage and epistasis are the three main reasons real inheritance departs from the simple predictions of a dihybrid cross, and they are exactly the sort of thing a chi-squared test can flag up. Inheritance so far has been about individuals and families; the same alleles, considered across a whole population, are the subject of the populations and the Hardy-Weinberg principle guide.