Quick questions on Types of mutation: point, silent, frameshift and chromosomal: HSC Biology Module 6

A point mutation changes a single base pair in the DNA. There are three structural sub-types.

Substitutions are further classified by what they do to the protein.

A frameshift is caused by an insertion or deletion of a number of bases not divisible by three. Every codon downstream of the mutation is shifted, so the amino acid sequence past that point is essentially random and a premature stop codon usually appears within a few codons. The resulting protein is truncated and non-functional.

A chromosomal mutation changes the structure or number of whole chromosomes. These affect many genes at once.

One base is replaced by another (e.g. A to G). The reading frame is unchanged; at most one codon is altered.

An extra base is inserted into the sequence.

A base is removed from the sequence.

Sickle cell anaemia is a single substitution (A to T) in the beta-globin gene, changing codon 6 from GAG to GTG. This is a missense mutation: glutamic acid becomes valine. The altered haemoglobin polymerises under low oxygen, deforming red blood cells.

Classify each of the following mutations: (a) a single base substitution that changes UCU to UCC, both coding for serine; (b) deletion of two bases in the middle of a gene; (c) duplication of an entire chromosome arm. [3 marks]

A 1500 bp gene undergoes a single base insertion at position 200. The original reading frame contained 500 codons including the stop. Predict how many amino acids will be altered compared to the original protein, assuming the new reading frame produces no premature stop until the end.

Compare the likely phenotypic consequences of (a) a silent point mutation in the centre of a coding sequence, (b) a nonsense mutation in the second codon of a gene, and (c) a translocation between chromosomes 9 and 22 in a haematopoietic stem cell. [2+2+2 marks]