Question

Alcohol dehydrogenase is an enzyme composed of several polypeptide subunits. It is normally expressed at high levels in the liver and the lining of the stomach. It is essential to metabolize alcohol, as without it, drinkers would become drunk faster and stay drunk longer. A scientist is studying mutations in mice that affect the activity of the enzyme. She finds that a heterozygote having a normal allele and a mutation that deletes the gene has 50% of normal enzyme activity. She has identified a new mutation and generated a homozygote for it. She crosses this homozygote to the heterozygote bearing the deletion. Half of the offspring have 75% of normal enzyme activity and half of the offspring have 25% of normal enzyme activity. Select all answers that correctly characterize the new mutation.

  

It is a gain-of-function mutation.

   

It is a partial loss-of-function mutation.

   

It is a loss-of-function mutation.

   

It is dominant negative.

   

It is a null mutation.

   

It is haploinsufficient.

Answer 1

Answer: Options B and F are correct
Explanation:
WT allele = Dominant = A
Mutant allele = Recessive = a

Parental cross: Aa X aa
Progeny: Aa Aa aa aa
Aa = 50% progeny = 75% of normal activity
aa = 50% progeny = 25% of normal activity

i. The WT allele is not sufficient to cause the WT phenotype in the heterozygous condition = Haploinsufficiency

ii. It is a partial loss of function mutation (aa exhibits 25% of the activity)

It is not a gain of function mutation as the activity is reduced due to the mutation.
It is not a complete loss of function mutation/null mutation (aa exhibits 25% of the activity)
It is not a dominant-negative mutation (If it is a dominant-negative mutation, Aa and aa should exhibit 0% activity)