Gene mutations (substitution, insertion and deletion) and their effects on the protein, chromosome mutations, mutagens, examples of genetic disorders such as cystic fibrosis and sickle-cell anaemia, and genetic screening and counselling.

What this dot point is asking

CCEA wants you to describe gene mutations (substitution, insertion and deletion) and their effects on the protein, describe chromosome mutations and mutagens, give examples of genetic disorders such as cystic fibrosis and sickle-cell anaemia, and explain genetic screening and counselling. It draws together the molecular genetics, inheritance and gene technology of the unit to explain how genetic disease arises and how it is managed.

Gene mutations and their effects

The effect depends on the type. A substitution changes only the codon it falls in. Because the genetic code is degenerate (most amino acids have more than one codon), a substitution may code for the same amino acid (no effect), a different amino acid (changing one amino acid in the protein), or a stop codon (cutting the protein short). An insertion or deletion is usually more serious: because the code is read in non-overlapping triplets, adding or removing a base shifts the reading frame of every codon after the mutation (a frame shift), so all the downstream codons change and the protein is likely to be completely non-functional. This is why a single deletion can be far more damaging than a single substitution.

Chromosome mutations and mutagens

Most mutations are harmful or neutral, but a rare beneficial mutation provides the variation on which natural selection acts. Mutations in body cells can lead to cancer if they affect genes controlling cell division, which is why mutagens such as ultraviolet light and tobacco smoke increase cancer risk. Mutations in gametes are passed to offspring and can cause inherited genetic disorders.

Genetic disorders, screening and counselling

Two much-tested examples link mutation type to disease. Sickle-cell anaemia is caused by a substitution mutation in the gene for a haemoglobin chain, changing one amino acid; the altered haemoglobin makes red cells sickle-shaped, so they carry less oxygen and can block vessels. Cystic fibrosis is caused by a recessive allele (often a deletion) affecting a membrane protein, leading to thick mucus in the lungs and digestive system. Because cystic fibrosis is recessive, two unaffected carriers (heterozygous) can have an affected child (a 1 in 4 chance). Genetic screening tests individuals or fetuses for disease-causing alleles, and genetic counselling helps families understand the risks and make informed choices. The benefits include early diagnosis and treatment and informed reproductive decisions, while the issues include difficult choices, anxiety, and concerns about privacy and the use of genetic information.

Examples in context

Example 1. Sickle-cell anaemia and a single base change. A single substitution in the haemoglobin gene changes one amino acid, altering the haemoglobin so red cells become sickle-shaped under low oxygen. This shows how even a one-base mutation can cause serious disease, connecting the molecular genetics of the unit to a real genetic disorder and to the cardiovascular content.

Example 2. Screening for cystic fibrosis. Couples with a family history of cystic fibrosis can be screened to see if they are carriers, and a fetus can be tested during pregnancy. The results inform reproductive choices and early care, but raise difficult ethical questions, illustrating both the benefit and the issues of genetic screening.

Try this

Q1. State the three types of gene mutation. [3 marks]

• Cue. Substitution (one base replaced), insertion (one base added), deletion (one base removed).

Q2. Explain why a deletion usually has a greater effect on a protein than a substitution. [2 marks]

• Cue. A deletion causes a frame shift, changing every codon after it; a substitution changes at most one codon.

Q3. Explain why two unaffected parents can have a child with a recessive genetic disorder. [2 marks]

• Cue. Both parents can be heterozygous carriers; a child inheriting the recessive allele from both is homozygous recessive and affected.