A genetic laboratory reports that a patient's PCR-amplified DNA fragment shows a pattern consistent with heterozygosity for a point mutation. On Sanger sequencing, the trace shows two overlapping peaks at the position of interest, one representing guanine (G) and one representing adenine (A). This finding indicates that the patient is heterozygous for which type of mutation if the original codon is GGA (glycine) and the mutant allele reads AGA?

• A Nonsense mutation converting glycine to a stop codon
• B Silent mutation with no amino acid change
• C Missense mutation converting glycine (GGA) to arginine (AGA) ✓
• D Frameshift mutation causing altered reading frame

Explanation

GGA encodes glycine, while AGA encodes arginine. A single G→A transition at the first position of the codon changes the amino acid from glycine to arginine — a missense mutation. Both alleles produce slightly different proteins (one normal, one with Gly→Arg substitution), which is why Sanger sequencing shows overlapping G and A peaks at that position in a heterozygous individual. A single nucleotide substitution affecting a single codon without introducing a stop codon is classified as a missense mutation.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.