Question

An enzyme, encoded by gene A, converts substrate X into product Y. Individuals with a dominant mutation in gene A over accumulate substrate X, which causes severe neurological symptoms. At the molecular level, this enzyme functions as a homodimer. A homodimer is a protein composed of two subunits that are encoded by the same gene. Let’s suppose you are able to purify subunits from cell samples and then mix them together under conditions in which they form homodimers, and you have an enzyme assay that can measure the accumulation of product Y. How would you distinguish the three common patterns of dominant inheritance: haploinsufficiency, dominant negative mutations, and gain-of-function mutations? In your answer, you need to describe what types of cell samples you would analyze, and how your results could distinguish between the three molecular explanations for dominant inheritance. Be quantitative in your answer.

Answer 1

gene A converts substrate X into Y.if there is any mutation in the gene then no conversion of substrate X into Y.That means without gene A or presence of mutated gene A quantity of X is more.there could be a situation in between complete conversion of X to Y.That situation is a case of haploinsuffiency(where both normal and abnormal genes comes into picture.where both are dominant or due to mutation copies of dominant gene is absent).

so here in this case let suppose 2 subunits contains genes A.that is case of dominant inheritence.if one unit contain A,then 50-50 situation arises.that is the case of haploinsuffiency.if gene A abesent from both subunits then it is a case of dominant negative mutation.if two subunits have both A,then it is gain of function mutation.