Brent Cornell

    
Sex linkage refers to when a gene controlling a characteristic is located on a sex chromosome (X or Y)

• The Y chromosome is much shorter than the X chromosome and contains only a few genes (50 million bp; 78 genes)
• The X chromosome is longer and contains many genes not present on the Y chromosomes (153 million bp ; ~ 2,000 genes)
• Hence, sex-linked conditions are usually X-linked - as very few genes exist on the shorter Y chromosome

X and Y chromosomes

    
Sex-linked inheritance patterns differ from autosomal patterns due to the fact that the chromosomes aren’t paired in males (XY)

• This leads to the expression of sex-linked traits being predominantly associated with a particularly gender

As human females have two X chromosomes (and therefore two alleles), they can be either homozygous or heterozygous

• Hence, X-linked dominant traits are more common in females (as either allele may be dominant and cause disease)

Human males have only one X chromosome (and therefore only one allele) and are hemizygous for X-linked traits

• X-linked recessive traits are more common in males, as the condition cannot be masked by a second allele

The following trends always hold true for X-linked conditions:

• Only females can be carriers (a heterozygote for a recessive disease condition), males cannot be heterozygous carriers
• Males will always inherit an X-linked trait from their mother (they inherit a Y chromosome from their father)
• Females cannot inherit an X-linked recessive condition from an unaffected father (must receive his dominant allele)

Inheritance of an X-linked Recessive Disease Condition

    
Red-green colour blindness and haemophilia are both examples of X-linked recessive conditions

• Consequently, they are both far more common in males than in females (males cannot mask the trait as a carrier)

When assigning alleles for a sex-linked trait, the convention is to write the allele as a superscript to the sex chromosome (X)

• Haemophilia:  X^H = unaffected (normal blood clotting) ; X^h = affected (haemophilia)
• Colour blindness:  X^A = unaffected (normal vision) ; X^a = affected (colour blindness)

Haemophilia

Haemophilia is a genetic disorder whereby the body’s ability to control blood clotting (and hence stop bleeding) is impaired

• The formation of a blood clot is controlled by a cascade of coagulation factors whose genes are located on the X chromosome
• When one of these factors becomes defective, fibrin formation is prevented - meaning bleeding continues for a long time
• Different forms of haemophilia can occur, based on which specific coagulation factor is mutated (e.g. haemophilia A = factor VIII)

Red-Green Colour Blindness

Red-green colour blindness is a genetic disorder whereby an individual fails to discriminate between red and green hues

• This condition is caused by a mutation to the red or green retinal photoreceptors, which are located on the X chromosome
• Red-green colour blindness can be diagnosed using the Ishihara colour test

The Ishihara Colour Test
(Click on the image to compare normal vision and colour blind vision)