Medical genetics: dominant negative effect: practice question

A Anatomy 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.

Try it

Anatomy · Medical genetics: dominant negative effect

Sample item

A baby with a glycine substitution in a COL1A1 chain has multiple fractures at birth, blue sclerae and a severe phenotype, while a parent with a null COL1A1 allele has mild disease. Which mechanism explains the severe case?

AHaploinsufficiency from half the usual amount of normal collagenBGain of function of an enzyme degrading collagenCLoss of heterozygosity at the wild-type allele in each cellDMutant chains disrupt the collagen triple helix, so the normal chains are lost too

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

The answer and the reasoning

D. Mutant chains disrupt the collagen triple helix, so the normal chains are lost too

In a dominant negative mutation the abnormal protein interferes with the product of the normal allele. Glycine substitutions disturb triple helix formation, so most collagen molecules are abnormal, whereas a null allele leaves half the normal amount (haploinsufficiency), giving mild type I disease.

Option by option

A. Haploinsufficiency from half the usual amount of normal collagen
Haploinsufficiency is the mechanism of the milder form in the parent.
B. Gain of function of an enzyme degrading collagen
No enzyme gain of function is involved.
C. Loss of heterozygosity at the wild-type allele in each cell
Loss of heterozygosity is a tumour suppressor mechanism and does not explain inherited osteogenesis imperfecta.
D. Mutant chains disrupt the collagen triple helix, so the normal chains are lost too (correct)
Correct. The abnormal chain poisons the helix and most molecules are defective.

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 Anatomy question

What is the answer to this Anatomy question?

The best answer is D, Mutant chains disrupt the collagen triple helix, so the normal chains are lost too. In a dominant negative mutation the abnormal protein interferes with the product of the normal allele.

Why is "Haploinsufficiency from half the usual amount of normal collagen" not the answer?

Haploinsufficiency is the mechanism of the milder form in the parent.

Why is "Gain of function of an enzyme degrading collagen" not the answer?

No enzyme gain of function is involved.

Why is "Loss of heterozygosity at the wild-type allele in each cell" not the answer?

Loss of heterozygosity is a tumour suppressor mechanism and does not explain inherited osteogenesis imperfecta.

What concept does this question test?

It tests Medical genetics: dominant negative effect in Anatomy. Glycine substitutions disturb triple helix formation, so most collagen molecules are abnormal, whereas a null allele leaves half the normal amount (haploinsufficiency), giving mild type I disease.

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 Medical genetics: dominant negative effect?

Learn every nerve by its route, its muscles and what a lesion looks like at the bedside. That one habit answers a large share of questions. Then use the flashcards and the other Anatomy 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.