Quick questions on Effects of mutation on amino acid sequence: coding vs non-coding DNA: HSC Biology Module 6

Silent mutation. A substitution that does not change the amino acid because the genetic code is degenerate (e.g. GGA and GGC both code for glycine). No effect on protein sequence.

Promoter mutations. Alter transcription factor binding, increasing or decreasing transcription. A weaker promoter for a tumour suppressor reduces its expression and increases cancer risk.

A substitution that does not change the amino acid because the genetic code is degenerate (e.g. GGA and GGC both code for glycine). No effect on protein sequence.

A substitution that changes one amino acid for another. Effect depends on:

A substitution that creates a premature stop codon (UAA, UAG, UGA). The protein is truncated and usually non-functional. Many Duchenne muscular dystrophy alleles are nonsense mutations in the dystrophin gene.

An insertion or deletion of a number of bases not divisible by three shifts the reading frame from the mutation onward. The amino acid sequence past the mutation is essentially random, and a premature stop codon usually appears within a few codons, producing a truncated, non-functional protein.

Alter transcription factor binding, increasing or decreasing transcription. A weaker promoter for a tumour suppressor reduces its expression and increases cancer risk.

Disrupt the GT...AG signals at intron boundaries, causing exon skipping or intron retention. Many beta-thalassaemia and Marfan syndrome alleles are splice-site mutations.

Change tissue-specific or developmental-stage expression.

A mutation in a microRNA gene can dysregulate dozens of target mRNAs.

Beta-globin gene, codon 6, sense strand changes from GAG to GTG (a single A to T substitution).

Codon 6 changes from GAG to GUG.

Glutamic acid (charged, hydrophilic) is replaced by valine (uncharged, hydrophobic). This is a non-conservative missense mutation at a surface residue.

The hydrophobic valine creates a sticky patch on the beta-globin surface. Under low oxygen, the deoxygenated haemoglobin (HbS) polymerises into long fibres, deforming red blood cells into rigid sickled shapes.

Sickled cells block capillaries (vaso-occlusive pain crises), are destroyed by the spleen (chronic haemolytic anaemia) and have a shortened lifespan. Heterozygotes are carriers with partial resistance to malaria, which explains the high allele frequency in malarial regions.