X-linked Inheritance: MDCAT Biology notes

Sex chromosomes and sex determination

In humans and Drosophila the female is XX and the male XY. A son receives his X from his mother and his Y from his father; a daughter receives one X from each parent. Other systems: XX-XO in the grasshopper (male has a single X and no Y) and ZZ-ZW in birds (female is ZW).

Genes on the X chromosome (with no partner on the Y) are X-linked. Because a male has only one X, he is hemizygous: a single recessive allele on his X is expressed. Inheritance of X-linked genes is criss-cross: a father passes his X to his daughters, who pass it to their sons.

Morgan's experiment

T. H. Morgan found a white-eyed male Drosophila among wild-type bright red-eyed flies. Red is dominant.

• White-eyed male ($X^wY$) $\times$ red-eyed female ($X^WX^W$): all $F_1$ are red-eyed, males and females.
• $F_1$ cross ($X^WX^w \times X^WY$): all females red; half the males red and half white. White eyes appeared only in males, showing the gene is on the X.

X-linked recessive traits

Examples: haemophilia (missing clotting factor), red-green colour blindness, testicular feminization. They are far more common in males. A female shows the trait only if both her X chromosomes carry the allele, so an affected girl must have an affected father and a carrier (or affected) mother.

Parents	Daughters	Sons
Carrier mother $X^HX^h$ $\times$ normal father $X^HY$	50% normal, 50% carriers	50% normal, 50% affected
Normal mother $X^HX^H$ $\times$ affected father $X^hY$	All carriers	All normal (0% affected)
Affected mother $X^hX^h$ $\times$ normal father $X^HY$	All carriers	All affected
Carrier mother $X^HX^h$ $\times$ affected father $X^hY$	50% carriers, 50% affected	50% normal, 50% affected

In the last cross each class of child (carrier girl, affected girl, normal boy, affected boy) is 25% of all children. A father never passes an X-linked allele to his son.

X-linked dominant traits

Example: hypophosphataemic (vitamin D-resistant) rickets. One copy is enough to show the trait. An affected father passes it to all his daughters and none of his sons; an affected heterozygous mother passes it to half her children of either sex.

Y-linked traits

Genes only on the Y chromosome (holandric genes), e.g. hypertrichosis of the ear pinna and the testis-determining gene, pass from father to every son and to no daughter. This is called straight inheritance.

Sex-influenced traits

Pattern baldness is autosomal, not sex-linked. Its expression depends on sex hormones: the heterozygote is bald in males but not in females, so it is commoner in men.

Common MDCAT traps

• An affected father cannot give haemophilia to his son; only the mother's egg carries an X to a son.
• Colour-blind mother $\times$ normal father: 0% normal sons, all daughters carriers.
• Haemophilia and colour blindness are recessive; hypophosphataemic rickets is the dominant X-linked example.
• Cystic fibrosis, thalassaemia and sickle cell anaemia are autosomal, not X-linked.
• Baldness is sex-influenced (autosomal), not X-linked.

Quick revision

• A man gets his X only from his mother.
• X-linked recessive traits are commoner in males.
• Carrier mother: half her sons affected, half her daughters carriers.
• Y-linked: father to all sons (straight inheritance).
• Grasshopper: XX female, XO male.