Mutation and genetic disorders

The essentials

Mutation is a change in the DNA sequence that results in a change in genotype and phenotype. Loss (deletion) or gain (insertion/duplication) of a DNA segment causes changes in chromosomes. A point mutation is a change in a single base pair, as in sickle-cell anaemia. Deletions and insertions of base pairs cause frame-shift mutations. Chemical and physical factors that cause mutations are called mutagens, such as UV radiation.

Pedigree analysis traces a trait through several generations of a family using standard symbols (square for male, circle for female, shaded for affected).

Mendelian disorders (single-gene):

• Haemophilia: X-linked recessive; a protein involved in blood clotting is affected, so a small cut may bleed for long. Carrier females transmit it to sons.
• Colour blindness: X-linked recessive defect in red or green cone cells. It occurs in about 8% of males and only about 0.4% of females.
• Sickle-cell anaemia: autosomal recessive; glutamic acid (Glu) is replaced by valine (Val) at the sixth position of the β-globin chain, because GAG changes to GUG. Under low oxygen, RBCs become sickle shaped.
• Phenylketonuria: autosomal recessive; lack of the enzyme that converts phenylalanine to tyrosine.
• Thalassaemia: autosomal recessive; reduced synthesis of α or β globin chains (a quantitative problem), unlike sickle-cell anaemia, which is a qualitative problem.

Chromosomal disorders arise from aneuploidy (gain or loss of a chromosome) caused by failure of chromatids to separate. Down's syndrome: trisomy 21; short stature, small round head, furrowed tongue, partly open mouth, palm crease, delayed development. Klinefelter's syndrome: 47, XXY male, with masculine development but some feminine traits and sterility. Turner's syndrome: 45, X0 female, sterile with rudimentary ovaries.

Common mistakes

• Polyploidy (extra whole sets) is common in plants; aneuploidy causes these human syndromes.