Molecular biology and genetics: dominant-negative mutation: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Biochemistry · Molecular biology and genetics: dominant-negative mutation

Sample item

A tumour suppressor protein functions as a tetramer. A heterozygous missense mutation in its DNA-binding domain abolishes far more activity than deleting one allele would. Which mechanism explains this?

AHaploinsufficiency, as half the normal amount of protein is madeBGain of function, with constitutive activation of the DNA-binding domainCDominant-negative effect, with mutant subunits inactivating mixed tetramersDGenomic imprinting, with silencing of the remaining normal allele

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

C. Dominant-negative effect, with mutant subunits inactivating mixed tetramers

If a mutant subunit still assembles into a tetramer, any tetramer containing it is non-functional. With equal expression, only 1 in 16 tetramers is fully normal, so activity falls far below the 50% expected with one deleted allele. Missense TP53 mutations act in this way.

Option by option

A. Haploinsufficiency, as half the normal amount of protein is made
Haploinsufficiency would give about 50% activity, as with a simple deletion.
B. Gain of function, with constitutive activation of the DNA-binding domain
The mutation abolishes activity, so this is a loss, not a gain, of function.
C. Dominant-negative effect, with mutant subunits inactivating mixed tetramers (correct)
Correct. Mutant subunits poison mixed tetramers, a dominant-negative effect.
D. Genomic imprinting, with silencing of the remaining normal allele
Imprinting restricts expression by parent of origin and is not described here.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is C, Dominant-negative effect, with mutant subunits inactivating mixed tetramers. If a mutant subunit still assembles into a tetramer, any tetramer containing it is non-functional.

Why is "Haploinsufficiency, as half the normal amount of protein is made" not the answer?

Haploinsufficiency would give about 50% activity, as with a simple deletion.

Why is "Gain of function, with constitutive activation of the DNA-binding dom…" not the answer?

The mutation abolishes activity, so this is a loss, not a gain, of function.

Why is "Genomic imprinting, with silencing of the remaining normal allele" not the answer?

Imprinting restricts expression by parent of origin and is not described here.

What concept does this question test?

It tests Molecular biology and genetics: dominant-negative mutation in Biochemistry. With equal expression, only 1 in 16 tetramers is fully normal, so activity falls far below the 50% expected with one deleted allele. Missense TP53 mutations act in this way.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Molecular biology and genetics: dominant-negative mutation?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.