Dominant mutations can be categorized according to whether the...

Question

Dominant mutations can be categorized according to whether they increase or decrease the overall activity of a gene or gene product. Although a loss-of-function mutation (a mutation that inactivates the gene product) is usually recessive, for some genes, one dose of the normal gene product, encoded by the normal allele, is not sufficient to produce a normal phenotype. In this case, a loss-of-function mutation in the gene will be dominant, and the gene is said to be haploinsufficient. A second category of dominant mutation is the gain-of-function mutation, which results in a new activity or increased activity or expression of a gene or gene product. The gene therapy technique currently being used in clinical trials involves the 'addition' to somatic cells of a normal copy of a gene. In other words, a normal copy of the gene is inserted into the genome of the mutant somatic cell, but the mutated copy of the gene is not removed or replaced. Will this strategy work for either of the two aforementioned types of dominant mutations?

Accepted Answer

Hello, everyone. Welcome back. Let's look at our next problem. It says hap low insufficiency in genetics describes a model of dominant gene action and deployed organisms in which a single copy of the wild type allele at a locus in a hetero ziggy's combination with a variant allele is insufficient to produce the wild type phenotype. What are the types of inheritance that are a result of gain of function mutations? I E the disease caused by the change in protein function as a result of mis sense mutations and a result of a mutant form of protein contributing to the formation of diners or multi MERS respectively. This question really throws a lot at us and it's kind of even tricky to parse out what we're supposed to be finding. So to sum it up, we're talking about models of dominant gene action. So when a genetic disorder is inherited in a dominant fashion, just one copy of the mutant allele is enough to cause the condition. And it's starting with hap low insufficiency and describing what that means in terms of dominant gene action and then asking us about two other types of dominant inheritance. So the second, we've got number one half, low insufficiency. Number two, it's saying the result of gain of function mutations. And number three, the result of a mutant form of protein contributing the formation of diamonds and multiples. So one is identified for us already. And two and three, we need to identify in our answer choices. So to think this through, it actually is kind of helpful to start with thinking about what does it mean when a condition is recessive. So in a recessive condition, having 50% of the normal protein of that wild type gene product is sufficient for the individual to be unaffected by the disease. So we know our genes produce proteins. And in this case, having one mutant alley, all means you've only only producing 50% of the normal form of this protein, but that's enough, you only need that you can still go on and you're not affected by symptoms. Um this is actually the case with many, many conditions. Uh so that's what a recessive condition is. I'm gonna put that in parentheses because that's not what we're looking for. We're looking for the different modes of dominant inheritance. So we saw number one mentioned here is half low insufficiency. So as our question says, when a single copy of the wild type allele in the hetero sickos combination with a variant allele is insufficient to produce the wild type phenotype. So in the case of happily insufficiency, unlike, are recessive condition, 50% of the normal protein is not enough. So the individual will suffer from a disease despite having only one very valuable because it's not enough to just have half the amount of protein that might occur. Because perhaps that protein has to be in a certain ratio with other proteins for normal metabolic functions to be carried out. But half low insufficiency is not what we're looking for. We're looking for the other types. So we're going to put a red X over the definition of half insufficiency to remind ourselves that we're not looking for that. So what are our other modes of dominant inheritance? Well, the first one says the result of gain of function mutations and and it says it's the disease caused by the change in protein function often as a result of MS sense mutation, why would gain a function be bad? Well, if the mutation causes the protein to have increased amount of activity more than it should have or an increased lifespan in a cell, think of early development and how important those timelines of different things turning on and off in development. So if we have gained a function protein doing what it shouldn't do. Uh That is another type of dominant inheritance because the mutant allele starts causing all these problems. So that form of inheritance, we just describe as autism, all dominant inheritance. You inherit one variant a little um it does this function that it shouldn't it has too much activity uh lives too long and it causes a genetic condition. So that's autism, a dominant inheritance. But then finally, we have this other type where we have a mutant form of protein that actually almost you might say poisons the function of the wild type protein most often by contributing the formation of diamonds or multi MERS. So your mutant protein combines in deleterious ways with your wild type protein and makes it unable to function causes problems with what it's supposed to do. So that when that happens, that is called a dominant negative effect. So again, that's when the mutant protein actually interferes with the function of the normal protein prevents the normal protein from carrying out what it's supposed to usually by forming diamonds or multiverse with the normal protein. So now all that understood what we're looking for would be autism. All dominant inheritance or gain of function mutation and the dominant negative effect. So let's look through our answer choices and we see that indeed choice. D says autism a dominant inheritance, dominant negative effect. But let's look through our other answer. Choices here. Choice A says Allah Gil syndrome and dominant negative effect, dominant negative is correct. But a legal syndrome is a genetic syndrome caused by hap low insufficiency. So that's why that's not going to be our correct answer. Choice. B says autism, a dominant inheritance, multiple existences, multiple existences is also a genetic condition caused by hap low insufficiency. So choice B also not our answer and choice. E alla Gil syndrome, multiple existences. Again, both of those caused by happen insufficiency. So not our answer choice. But again, when we're looking for the types of inheritance that a result of gain of function mutations and the result of a mutant form of protein contributing to the formation of dimmers or multi MERS. We've got autism all dominant inheritance and the dominant negative effect, which is choice d see you in the next video.

Key Concepts

Haploinsufficiency

Gain-of-Function Mutations

Gene Therapy

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