Monoallelic Expression

by Georgina Cornwall, PhD

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    00:01 Now, we also can have monoallelic expression. That is only one allele is expressed. We’re not talking about the X-inactivation where one is crumpled up. But for some reason and it could be random, we may only have expression of one allele. So, let’s look at some of the ways in which we might get monoallelic expression.

    00:27 First of all, we could have a random choice as I just said. It could happen because of genomic imprinting.

    00:35 We’ll take a look at both of those cases as well as it happening from X-inactivation. So these are three distinct ways that we may end up with only one allele being expressed even though both of them are actually there. So, when we look at monoallelic expression being a random choice, there are two possibilities that have surfaced. One of those is allelic silencing, where literally one allele is silenced by epigenetic mechanisms.

    01:08 So, either we have DNA methylation or histone modification or one of the epigenetic mechanisms that literally makes the DNA inaccessible to the transcriptional process. The other means we could have is by somatic rearrangement.

    01:24 This is one of those places where we talked about having an inversion. Let’s say the inversion happened right within a gene. So, the breakpoint from one of the ends of the inversion is right in the middle of the gene.

    01:37 That piece of DNA flips and is inserted back in. Now, we’ve broken a gene. So randomly, that gene may no longer be able to be expressed leaving only one allele or monoallelic condition. The next thing we have to consider is genomic imprinting. Genomic imprinting is going to come up in much more detail when we look at it in the lectures on single-gene disorders. Because genomic imprinting is something that happens to a chromosome, it’s marked epigenetically so that it is expressed one way in a male than it is in the female. So, let’s take a quick look at how that happens. We’ll start with the top half of this figure. You can see that we have an oocyte all the way over on the right hand side. That oocyte has been fertilized by a sperm. We see that it has a pink chromosome indicating that that chromosome came from the maternal parent. Now, the male sperm comes along and fertilizes the egg. It brings in a chromosome. That chromosome, the blue one is from the male parent.

    02:53 So we can follow that in both directions. Those chromosomes in those cells will stay marked the way that they are as those cells go through growth and development and we’ve become an adult. So, the adult will have exactly the same chromosomal markings of a paternally inherited chromosome and a maternally inherited chromosome.

    03:17 Those markings will stay throughout that person’s life until they, themselves make gametes. That’s where we see the grayed out version of the chromosomes here because the epigenetic markers are actually removed from a chromosome during the formation of gametes or sperm and eggs so that they can be relabelled as being from an egg or from a sperm. Thus, when we continue on and have fertilization, they are labelled as maternally or paternally inherited. Now, why does this even matter? It matters because the expression, there are some conditions, one of which we’ll look at specifically in much more detail later in which it has a completely different manifestation, whether the mutation was inherited paternally or maternally.

    04:09 So, one individual could have a completely different outcome based on which chromosome or the mutation coming from the parent, the male parent or the female parent. It’s certainly a complex situation but trust me, we will investigate it in much more detail later. It will make much more sense or maybe it will become more confusing.

    04:32 But it’s certainly an interesting case. It is definitely distinct from X-inactivation which is something we’ve looked at before that also impacts gene expression dependent on sex. But it’s entirely different because it doesn’t depend on which parent it comes from. X-inactivation, we’ve considered certainly before. Dosage compensation is what has to happen. Males have one X chromosome and a Y. Apparently, in the case of the X chromosome, that is the perfect amount. Females, well we happen to have a little bit too much and so one of them needs to be inactivated.

    05:15 Which one is inactivated? It’s actually fairly random as far as we know. We seem to say these things are random all the time but it probably just means that we don’t really know yet what causes them to be inactivated.

    05:29 So, one chromosome is chosen to be inactivated. It condenses up. By a consequence or not, it happens to be epigenetically modified so that we have the DNA methylation or histone modifications or anything that helps this DNA crumple up and be inaccessible to the transcription mechanisms. So, the progeny of each of these two cells which could either have the pink one inactivated or the blue chromosome inactivated, all of them will have the same progeny, all of which have the same chromosome inactivated. You might recall from the previous course that that results in females in essence being a mosaic. So by mosaic, we use the example of a calico cat back then but even our sweat glands are often mosaic because they can be X-linked. So, we’ll have patchy networks of sweat glands. It could be that more cells have the maternally inherited chromosome or more cells have the paternally inherited chromosome. Of course, it really depends on where those genes are expressed, which cells they’re expressed in. So, we can be a mosaic in many different ways because of this dosage compensation concept.

    06:54 Again, distinct though from the imprinting that we saw. So, keep those distinct in your mind. We’ll examine more conditions that involve those specific mechanisms later on in the course. So, what we need to understand from this lecture is that there are all sorts of different ways that allow us to have just the right amount of DNA being expressed or protein products resulting from the DNA. Often, changes in the level of gene expression can go unnoticed. But on occasion, even a very small change can have a huge clinical consequence. That’s where we see the gene modifications that result in some of the genetic disorders that we’re going to see throughout this course.

    07:45 So, I’m really excited to move on to the next section and help us explore chromosomal mutations. Thanks so much for listening.

    About the Lecture

    The lecture Monoallelic Expression by Georgina Cornwall, PhD is from the course Introduction to Medical Genetics. It contains the following chapters:

    • Monoallelic Expression
    • Monoallelic Expression: X-Inactivation

    Included Quiz Questions

    1. One allele is not present in the genome.
    2. One allele is randomly chosen.
    3. One allele is imprinted to not get expressed.
    4. One allele is part of the inactivated X chromosome.
    5. One allele is epigenetically silenced.
    1. Genomic Imprinting follows Mendelian inheritance.
    2. Some conditions may have different manifestations based on whether the mutation is paternally imprinted or maternally imprinted.
    3. Imprints are re-established during gametogenesis.
    4. Imprints remain part of our whole life (developmental and adulthood).
    5. Genomic Imprinting is an example of epigenetic inheritance.
    1. Barr body
    2. Barr chromosome
    3. Bar chromosome
    4. Bar body
    5. Bar allele
    1. Allelic dominance
    2. Epigenetic modifications
    3. X-inactivation
    4. Genomic Imprinting
    5. Barr body formation

    Author of lecture Monoallelic Expression

     Georgina Cornwall, PhD

    Georgina Cornwall, PhD

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