Sex-linked Inheritance — Haemophilia and Colour Blindness

Sex-linked inheritance refers specifically to the characteristic pattern by which genes located on one of the two SEX chromosomes — in practice, almost always the X chromosome, since the much smaller human Y chromosome carries only a comparatively small number of genes — are transmitted from parent to offspring, a pattern that differs in an important, predictable way from the inheritance of genes located on the ordinary autosomes. Because a human male carries only a SINGLE X chromosome in his cells (genotype XY), any recessive allele that happens to be present on that one X chromosome is expressed directly and fully in his observable phenotype, since there is no second X-linked copy of the gene present anywhere in his cells that could possibly mask or dominate it. This single structural fact is precisely why X-linked RECESSIVE disorders are observed, consistently and predictably, far more frequently in human males than in human females: a female, carrying two X chromosomes (genotype XX), needs to inherit the same recessive allele on BOTH of her two X chromosomes simultaneously before the disorder can be expressed in her own phenotype, whereas a male needs to inherit that very same recessive allele on just his ONE single X chromosome for the disorder to be expressed immediately and fully in him.

Haemophilia is a well-studied, and historically famous (through its transmission within several European royal families), X-linked recessive disorder of humans, in which an individual's blood fails to clot normally because of a genetically caused deficiency of one of the essential blood-clotting proteins (most commonly clotting Factor VIII, in the most common form of the disease), resulting in prolonged, and potentially dangerous, bleeding even following comparatively minor injuries that would not trouble an unaffected individual at all. Consider a phenotypically entirely normal but genetically carrier (heterozygous, genotype XHXh) woman who marries a phenotypically normal, non-haemophilic man (genotype XHY): because every SON born to this couple necessarily receives his single X chromosome from his MOTHER (his Y chromosome instead comes from his father), each son has an independent 1/2 (50%) probability of inheriting the mutant Xh allele from his carrier mother and consequently being born haemophilic (genotype XhY), and an equal 1/2 probability of instead inheriting the normal XH allele and being unaffected (genotype XHY). Every DAUGHTER born to this same couple, by contrast, necessarily receives one X chromosome from each of her two parents — always a normal XH allele from her unaffected father, and either an XH or an Xh allele from her carrier mother — so every daughter is phenotypically entirely normal (since she always has at least one normal XH allele, inherited from her father), yet exactly half of these phenotypically normal daughters (genotype XHXh) are themselves, like their mother before them, silent carriers of the haemophilia allele, capable of passing it on, undetected, to a future generation. …