Linkage

When genes are only present on one sex chromosome, they are referred to as being sex-linked.

Sex linkage in genetics

All humans have 22 autosomal chromosomes (any chromosome that is not a sex chromosome) pairs and one pair of sex chromosomes. Biological females have two X chromosomes and biological males have one X and one Y chromosome.

The process of meiosis produces haploid cells. These only contain a single set of unpaired chromosomes. This means that for females, all gametes will have one X chromosome, while half of the alleles that a male produces will have an X chromosome and half will have a Y chromosome.

Recall that a child will inherit one sex chromosome from their mother and one from their father. Because of this, a child inheriting two X chromosomes (XX) will be biologically female, whereas a child inheriting one X and one Y chromosome (XY) will be biologically male.

The X chromosome is much longer than the Y chromosome, and most regions of the X chromosome do not have a homologue in the Y chromosome. This means that a single recessive allele on the non-homologous portion of the X chromosome is enough for the corresponding trait to be expressed. After all, there can be no dominant allele on the Y chromosome to mask it. Because of this, the sex of an individual greatly affects their chances of inheriting certain recessive alleles or defective genes which lead to disease.

For females, there are three possible phenotypes:

• Neither suffer nor carry the disease (what is designated as ‘normal’ in some textbooks.)
• Carrier (has one allele but doesn't suffer the illness.)
• Has the disease.

For males, there are only two phenotypes:

• Neither suffer nor carry the disease.
• Has the disease.

Why can men not be carriers of sex-linked genetic diseases?

Men can’t be carriers of sex-linked genetic diseases because they have only one X chromosome. The Y chromosome is not a homologous chromosome. Therefore, the genetic make-up of the trait isn’t twofold.

Can males be carriers of diseases?

A carrier for a disease has the allele for a trait but doesn’t usually show symptoms. They will be heterozygous (e.g. Aa or Hh) and can pass the allele for the disorder to their offspring. If the offspring is homozygous-recessive (aa or hh) then the offspring will be infected. Males only have one X chromosome. A single recessive gene on that X chromosome will be expressed in the phenotype because there are no corresponding genes on the Y chromosome. This means males cannot be carriers.

In women, a recessive allele on an x chromosome is usually masked in their phenotype by a dominant allele on the other X chromosome. This is why women are more likely to be carriers and not have the gene expressed in their phenotype.

How can we predict the inheritance of colour blindness?

Some of the genes for red-green colour blindness are sex-linked and found on the X chromosome. Let the allele B represent healthy vision and b represent colour blindness. The capital (B in this case) always denotes the dominant allele and lower case (b) denotes the recessive allele.

The following diagram shows how two healthy parents (a healthy male and a carrier female) can have offspring with colour blindness. As the Y chromosome does not have either gene it is just represented as Y.

Parent’s phenotypes: normal vision normal vision

Parent’s genotypes: Xᴮ Xᵇ XᴮY

Gametes: Xᴮ Xᵇ XᴮY

Table 1. Inheritance of colour blindness from a healthy father and a carrier mother

50% of offspring will be male, half of whom will be colour blind. This means 25% of offspring are colour blind males. On the other hand, none of the females is colour blind. A colour blind male can only have inherited the condition from his mother since he would have only gained a Y chromosome from his father.

How can we predict the inheritance of haemophilia?

Haemophilia can lead to slow and persistent internal bleeding, particularly in joints, and can be lethal if left untreated. Because many individuals with this disease do not survive until reproductive age, it is relatively rare. The overwhelming majority of its sufferers today are male; only a small percentage are female. This is in part due to the fact that many haemophiliac females die from extreme blood loss when menstruation begins.

Haemophilia can be caused by a number of things, but one is a recessive allele on the X chromosome which codes for a faulty protein involved in the clotting process. When a carrier female and a healthy male have offspring, 25% will be haemophilic males, as predicted by the diagram below. While males can inherit haemophilia from their mothers, they cannot inherit it from their fathers. 25% of the offspring will also be carriers XᴴXʰ. The following diagram shows a cross between a non-carrier male and a carrier female.

Parent’s phenotypes: Carrier mother Non-carrier father

Parent’s genotypes: XᴴXʰ XᴴY

Gametes: XᴴXʰ XᴴY

Table . Inheritance of haemophilia from non-carrier father and carrier mother

Haemophilia is a recessive trait. Thus, non-carrier genotypes are depicted as Xᴴ, while diseased genotypes are depicted as Xʰ.

Pedigree charts

Pedigree charts are a useful method of tracing the inheritance of sex-linked traits. They have specific characteristics such as:

• Males are represented by squares.
• Females are represented by circles.
• The shading in each shape represents the absence or presence of a trait in question – usually the phenotype.
• Shading indicates the presence of a trait.

The following is an example pedigree of a non-diseased male and a carrier female for the phenotype of colour blindness.

As shown above, neither parent is colour blind. However, one of the offspring is colour blind. This means that one of the parents is a carrier. Recall that males only have one X chromosome, the female parent must be the carrier.

Autosomal linkage

Autosomal linkage can seem really complicated because there's a lot to think about at once but if we break it down, you’ll see that it's not as hard as it first appears.

1. Linked genes are genes that occur on the same chromosome.
2. All the genes on a single chromosome are said to form a linkage group.
3. Autosomes are all chromosomes except sex chromosomes.
4. When the same autosome carries two or more genes, we call it autosomal linkage.
5. These linked genes remain together during meiosis. They pass onto gametes and then offspring together (this is assuming there is no crossing over.)
6. Segregation in accordance with Mendel's law of independent assortment does not occur.

Genes on the same autosome have a higher chance of being inherited together. Recall that heterozygous individuals possess two different alleles of the same gene. When two genes T and B with heterozygous alleles are on different chromosomes, there would ordinarily be four different combinations, and the offspring would have phenotypes with a 9:3:3:1 ratio (see the article on Inheritance for more details.) However, when genes are linked, there are only two possible combinations: (TB) and (tb), written in brackets to represent linkage. The resulting phenotype ratios are therefore easier to deal with.