If you've ever taken a biology class before, you've heard of Gregor Mendel. Mendel was an Austrian monk and the first person to uncover some basic principles of how genes are passed on or inherited. I see him as lucky because the traits he chose to study; pea plant in height, color, and texture are very rare example of genes that are inherited and expressed in a very straightforward manner, what we call Mendelian inheritance. So Mendelian inheritance refers to genes that are inherited and expressed in a very particular pattern. You have a genotype, which describes which genes you have and a phenotype, which is the results of those genes, like your hair color. Genes can be dominant, meaning you almost always see the phenotype or recessive, meaning you only see the phenotype if there isn't a dominant gene present. Remember, you have two copies of each gene. You get one from each of your parents, and punnett squares are a way of tracking how genes are inherited and used to make predictions. I'll come back to punnett squares of the real life example in a minute. As I mentioned at the beginning of this lecture, gene that are inherited in this way are the exception, not the norm. For example, there can be incomplete dominance. Incomplete dominance is when an intermediate phenotype is expressed as an individual's heterozygous. Heterozygous means that I have one dominant gene from one parent and a recessive gene from the other. So the classic example of certain kinds of flowers. To get a pink flower, one parent is red and the offspring has inherited one red gene and the other parent is white, and the offspring has inherited one white gene. The resulting offspring is a mix of the two or pink, mix of red and white. There is also codominance as well. Codominance means that regardless of what gene variant you have, both will be expressed. An example of codominance is blood types. Let's look at an example of blood type a little bit more closely. Humans can be A, B, AB, or O. You may also be familiar with being A positive, A negative. Positive or negative refers to whether or not there's a protein on blood cells called the Rh factor. Let's return to these letters. A and B refer to certain kinds of sugars that are on the outside of blood cells. Let's just say here's a blood cell and on that blood cell we have A sugars. This would be for someone who has type A blood. Then let's say we have here someone who is type B blood, so they've got B sugars stuck on their blood cells. So where codominance comes into this, is somebody who has a gene for A, they will have A sugars on their blood cells, that they have a gene for B will also have B on their blood cells as well. So how about somebody who is O? So we can think of O as being no. So in this case there's no sugars at all. This is why O negative blood, particularly as universal donor, because there's no sugars there's nothing that can react with the immune system. So anybody can accept O negative blood. AB positive blood is also known as universal recipient. This person can accept either positive or negative blood or A blood, B blood, AB blood, or O blood. Let's apply what we have here to a real-world example. So my son and I are AB, O incompatible. So if we look at my blood cells, I'm O positive. So I have the RH factor that there is no sugars stuff on the outside of my blood cells. But if we look at my son, he has A blood. So he has A sugars stuck on his cells. When my son was being born, my body recognized his blood as foreign and attacked. So this resulted in the destruction of his blood cells, when blood cells are destroyed, a compound called bilirubin is produced and that builds up and leads to judders. So he ended up spending the days the first few day's life on a belly bed to help break down that bilirubin. So if I'm O, how is it possible that I have a son who is A? Well, we have to blame my husband. Let's break this down a little bit of the punnett square. So here is the punnett square. Then I'll put my genotype at the top. So going back to our discussion of codominance because I'm O positive, that means that I can't have a gene for A or B. So my genotype has to be O, O. My husband must have at least one gene for A. We don't know what his other is because we're not sure what his blood type is, and even if we did know, we might not know for sure. So I can only pass O onto my offspring. So basically we just drop this O down. Husband passes on and A and then we don't know. Because my husband could be AO, he could be AA, and he could be AB, we're not sure. If we knew for sure that his blood type is AB, we would know that his genotype is AB as well though. The minimum we know in terms of me having future children is that there's a 50 percent chance. There's 1, 2, 3, 4 chances, so 2 out of 4 chance, 50 percent chance of having a biocompatible event. If my husband's genotype is either AA or AB then we know that that it's 100 percent chance of happening again. If we draw these planet squares, so if we have OO, my husband is AO. AO, AO, OO, OO so 50 percent chance. If he is AA, and we are in OO, AO, AO, AO, AO, so 100 percent chance. If he happens to be AB, so AO, AO, BO, BO, so 100 percent chance of being a biocompatible event. One way that we can know for sure if my husband's genotype is, is if I have an offspring, had a child rather, who is B blood, if my first child has A blood and my second child has B blood, that means my husband has to be AB. If I don't have a child with O blood, well, that means my husband has to be AO because otherwise there would be no way to have a child with O blood, because they got an O for me and an O my husband. If I have another child that's A, well, we don't know if that's because my husband is AO or AA. In this example we saw how to use Punnett squares for predicting blood types. Punnett squares are one tool for predicting inheritance and pedigrees or another. Pedigrees are particularly useful for tracking genetic patterns across generations and determining how a trait is transmitted between those generations. As shown in this image, males are shown as boxes and females are circles. A pedigree can be used, for example, to determine if a disease or condition is sex-linked or not. Sex linkage is an interesting phenomenon that also doesn't follow Mendelian inheritance. Remember that humans have 23 pairs of chromosomes, and that the 23rd pair is what are called sex chromosomes. Generally, as there are exceptions, like everything else in biology and science, males have an X and a Y and females have two X chromosomes. Y chromosomes have one function and that is to specify male during embryonic development. The default developmental program is female. Without the activation of genes on the Y chromosome, a female child will result. In the case of mutations where those genes on the Y chromosome do not get turned on, you have an individual who appears physically female, but is genetically male. The X chromosome, on the other hand, carries over 1,000 protein-coding genes, including genes that are linked to color blindness and hemophilia. Since males only have one X chromosome, they are more likely to be affected by X-linked traits. There's only one chance, so to speak, to get a normal or a wild-type version of the genes. On a pedigree, if a disease or condition is X-linked, we would look and see that there are more males affected than females. For non sex-linked genes, the pedigree will vary depending on if it's a recessive or a dominant gene. Let's consider albinism for a minute. Albinism is lack of pigment in your skin or your hair. Albinism is a recessive trait, and so in order for someone to have albinism, they must have two recessive genes. On a pedigree, you would only see affected individuals from parents who were either affected themselves or who are carriers. A carrier is an individual with one wild type and one mutant copy of a gene. They themselves are unaffected, but they can still pass a gene on to their offspring. Women can be carriers of sex-linked traits as well. A woman, for example, can carry the mutant form of the gene controlling color blindness, but not be colorblind herself. If she has a son and passes mutant form of that gene controlling color blindness unto her son, her son will be colorblind. Mendel was lucky enough to study genes that are inherited in a straightforward manner. In the examples I've given so far are also fairly straightforward. However, I want to emphasize that this is the exception and not the norm. The majority of genes and protein products work in conjunction with one another to influence gene expression. In fact, we're only now just beginning to understand the interactions between genes, gene expression, and the environment, also known as epigenetics. I mentioned epigenetics earlier in this module. Epigenetics is a new field. The very first papers came out in the 1990s and the official term epigenetics was not coined until 2008. Epigenetics refers to heritable changes in gene expression that do not resolve from changes in the DNA sequence or from mutations, which we talked quite a bit about in the last module. These heritable changes alter how accessible these genes are. So again the more easy it is to access the more likely it is to be expressed. The really fascinating part of our epigenome is that it can change, although our genes, what genes we get from our parents are static, our epigenomes are not. So let's consider twins for a minute. Twins have identical genetic material, but as twins age they can actually have very different health histories. Why does that happen if they share the same genes? It's because their epigenomes are changing over time causing twins to actually become less identical as they age. Being able to easily change our epigenome can be good or bad. It's good because if we have damaging epigenetic changes then we can reverse them. So this could be a viable treatment option for diseases like cancer. However the easily changed epigenome means we're susceptible to the damaging changes as well. Epigenetic changes can be passed to our offspring as well. An intergenerational trauma is an example of a how epigenetic changes can pass on to children. One landmark study followed up on children who were in utero during the Dutch Hunger Winter in the 1940s. During World War II the Dutch attempted to help allied forces by interfering with railroad operations used by the Nazis to move troops. The Nazis punished the Dutch by blocking food supplies causing a famine that lasted until the Netherlands were liberated the following spring. These children went on to have altered metabolism and stress responsiveness as a result. They weighed more, they had higher blood triglyceride levels, and they had elevated cholesterol as well. They were also more likely to die prematurely. Evolutionarily this makes sense, if mom faces significant stress this prenatal program can help the offspring, the prime to come into this stressful environment. They need to be able to pack on pounds so that they can survive a famine. This is an example of an experiment done at Emory University that exemplifies intergenerational trauma and epigenetics. If you've ever taken a psychology class before you may be familiar with a phenomenon called classical conditioning. This was most famously exemplified through the work of Pavlov, who demonstrated the relationship between ringing a bell before giving dogs food and the dogs starting to salivate. So eventually all Pavlov needed to do is ring the bell to get the dogs to salivate. There's an application of this that involves fear. Here's my mouse. [inaudible]. This mouse has been classically conditioned to be afraid of the smell of almonds. Let's call that an almond there. Because every time the mouse smell almonds it received just a small foot shock. Ouch. The mouse started to associate the shock to the smell of almonds. So anytime the mouse smelled almonds he would freeze and afraid, "I don't want to do this." Eventually there was no need to have the shock anymore because just the smell of almond was enough to make the mouse freeze. What's important here is that these were all male mice that were classically conditioned. So when you take these male mice, and so all show that these are the classical conditioned ones. We'll just do a little lightning bolt here. We took these mice and we cross them with females who were not here conditioned. Then now we have baby mice. It should look a little bit like my almond. But well we'll roll with it. Here's our little mice. So what's interesting is that if these mice are exposed to the smell of almonds, we'll make our almonds now green to make it stand out. So almond smell is now green. They did the exact same thing that their fathers did, they freeze. So even though this generation of mice was not fear conditioned nor did they have any contact with their father whatsoever, they were still afraid of the same thing that their father was afraid of. So that gene was actually passed in the sperm, the progeny, the offspring had the exact same fear responses to the father. This is an example of how epigenetics works and how intergenerational trauma works. Because even though the offspring didn't experience this fear or this trauma they're still programmed to be afraid of it. To wrap up, how genes are inherited and expressed isn't really that straightforward. In fact some have even suggested that we shouldn't teach Mendelian genetics at all, because it gives the wrong ideas about how our genes work. This can be particularly problematic when exploring everything from social justice issues to making sense about easily accessible genetic information. Now all you need to do to find out information about your genes is go to the store and pick up an at-home testing kit. In the next module we'll discuss more about at-home genetic sequencing and other hot genetic technologies.
