Q.72 A protein coding gene in the mouse was mutated, such that the resultant protein was nonfunctional. The phenotypic effect
of the mutation was observed in homozygous mutant mice, in heterozygous mice that inherited the mutation from the
mother, and in heterozygous mice, that inherited the mutation from the father.
This suggest that –
1. the gene is imprinted.
2. the mutation acts as a dominant negative.
3. the gene possibly has more than two alleles
4. the gene is X-linked.
Mouse Gene Mutation Phenotype in All Heterozygotes: Q.72 Dominant Negative Answer
A nonfunctional protein mutation showing phenotype in homozygous and both maternal/paternal heterozygous mice indicates the mutant actively interferes with wild-type protein function regardless of parental origin.
Correct Answer
Option 2: the mutation acts as a dominant negative. The mutant protein disrupts normal protein activity in heterozygotes from either parent.
Option Explanations
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Option 1 incorrect: the gene is imprinted. Imprinted genes silence one parental allele; maternal heterozygotes would show phenotype but paternal ones wouldn’t (or vice versa).
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Option 2 correct: mutation acts as dominant negative. Mutant protein forms defective complexes with wild-type, poisoning function in all heterozygotes irrespective of inheritance source.
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Option 3 incorrect: gene possibly has more than two alleles. Standard biallelic inheritance; multiple alleles don’t explain parent-independent heterozygous effects.
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Option 4 incorrect: gene is X-linked. X-linked recessive shows phenotype mainly in hemizygous males; heterozygous females usually asymptomatic due to X-inactivation mosaicism.
Mechanism Insight
Dominant negative mutations often occur in multimeric proteins where defective subunits poison wild-type complexes (like p53 tetramers or Ras signaling).
Exam Strategy
Key clue: phenotype in both maternal and paternal heterozygotes eliminates imprinting/X-linkage. Link to protein complex disruption patterns in genetics questions.
