Sex linkage is the phenotypic expression of an allele that is related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of expressing the trait. Since, in humans, there are many more genes on the X than there are on the Y, there are many more X-linked traits than there are Y-linked traits.

In mammals, the female is the homogametic sex, having two X chromosomes (XX), while the male is heterogametic, having one X and one Y chromosome (XY). Genes that are present on the X or Y chromosome are called sex linked genes.

Linkage overview

X-linked recessive traits are expressed in all heterogametics, but only in those homogametics that are homozygous for the recessive allele. For example, an X-linked recessive allele in humans causes haemophilia. Haemophilia is much more common in males than females because males are hemizygous - they only have one copy of the gene in question - and therefore express the trait when they inherit one mutant allele. In contrast, a female must inherit two mutant alleles, a less frequent event since the mutant allele is rare in the population.

The incidence of recessive X-linked phenotypes in females is the square of that in males (squaring a proportion less than one gives an outcome closer to 0 than the original). If 1 in 20 males in a human population are green color blind, then 1 in 400 females in the population are expected to be color blind (¹/₂₀)*(¹/₂₀).

X-linked recessive inheritance

X-linked traits are maternally inherited from carrier mothers. Each son born to a carrier mother has a 50% probability of inheriting the X-chromosome carrying the mutant allele. There are a few Y-linked traits; these are inherited from the father.

In classical genetics, a reciprocal cross is performed to test if a trait is sex-linked.

Types of links

X-linked recessive

X-linked inherited diseases occur far more frequently in males because they only have one X chromosome. Females must receive a copy of the gene from both parents to have such a recessive disease. However, they will still be carriers if they receive one copy of the gene. Recessive genes on the X chromosome that cause serious diseases are usually passed from female carriers to their ill sons and carrier daughters. This is because males, who always have the disease and are not just carriers, would have to father a daughter to pass on the gene. This is unlikely because severe genetic diseases often cause death in childhood or early adulthood. Even those males who survive childhood are unlikely to father children because a sickly male will be less likely to find a mate. However, if the disease shows up late in life, or is not severe, he will pass the gene to all of his daughters. He can not pass it to his sons because a male receives his X chromosome from his mother. A mother with one copy of the gene has a 50% chance of passing it to her children of both sexes, but her daughters will just be carriers of the gene unless their father has it too.

Diseases well known for their X-linked recessive inheritance are Haemophilia (types A and B), and color blindness.

X-linked dominant

There are few examples of X-linked dominant diseases; the best known in this category is vitamin D resistant rickets. Other examples are:

• Incontinentia pigmenti

Y-linked

• Various failures in the SRY genes

Sex-linked traits in other animals

• Calico or tortoiseshell cats, those which have orange-and-black fur.
• White eyes in Drosophila melanogaster flies, the first sex-linked gene ever discovered.

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