Single-gene disorders and pedigrees

Monogenic (single-gene) diseases come from a fault in one gene; over 10,000 are known. They follow Mendel's laws, so their inheritance can be traced with a pedigree: a family tree drawn with standard symbols (squares for males, circles for females, shaded for affected).

Autosomal recessive: the gene is on an ordinary chromosome, and two faulty copies are needed to cause the disease. A person with one faulty copy is a carrier: healthy, but able to pass it on. If two carriers have a child, there is a 1 in 4 chance the child is affected.

• Sickle cell anaemia: a fault in the haemoglobin beta gene (on chromosome 11). Red cells become sickle-shaped after giving up their oxygen, block blood vessels and break easily. It is common in the Deccan plateau of central India.
• Others: cystic fibrosis, Tay-Sachs disease, phenylketonuria.

Autosomal dominant: one faulty copy is enough. In achondroplasia (a form of dwarfism), D/d people are affected, and D/D is often lethal. Huntington's disease is another example.

X-linked recessive: the gene is on the X chromosome. Since males have only one X, they are affected far more often. A carrier mother passes it mainly to her sons. An affected father passes it to none of his sons (they get his Y) but makes all his daughters carriers (they all get his X). Examples: haemophilia (a fault in clotting factor VIII or IX) and Duchenne muscular dystrophy (a fault in the muscle protein dystrophin).

X-linked dominant: an affected father passes it to all his daughters and no sons; an affected mother to half her children. Examples: hypophosphataemic (vitamin D-resistant) rickets and Alport syndrome.