How are genes inherited?
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How are genes inherited?
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Section 1: Intro
Chapter 15. How are genes inherited? Some people look the same or similar to their parents. This is because they share some of their genes. Genes are really passed on from one person to the next, where some genes are shuffled around.
Section 2: The genome
Now, let us look at inheritance of genetics. Let us first start with the structure of the genome. The genome itself is basically a term that describes the whole genetic information of a person. This is frequently lined up into letters and genes are dispersed and they only make up 1% of the whole genetic code, which consists of 30 thousands of such genes. As I described in what genes are in another chapter, the human body has a nucleus which contains the chromosomes. The chromosomes contain the DNA genetic letters. The chromosomes are kind like boxes that contain around one thousand genes.
There are different types of chromosomes. If you list them all up, you will always see that there are two copies of each chromosome. There is chromosome number 1, 2. They all have different sizes. As I said, each one of them will have around 1 thousand different genes on them. There are the X and Y chromosomes which we will talk about them in a minute. Now, I have colored them in pink and blue because the pink ones are all from the mother and the blue ones are from the father. This is why we have two copies of every chromosome. You get one from your father and one from your mother and that is why you kind of have your mother’s eyes and your father’s smile. They are really shuffling their genes to create a new combination which then is you.
As I said, one thousand different genes per chromosome. For example, the lactase gene for lactose intolerance sits on chromosome number 2. The factor-V gene for thrombosis is chromosome number 1. One example that I have made in the other chapter, COL4A5, sits on the X chromosome. So, there are different locations for different genes.
Section 3: Heredity
Now, let us look at heredity. Let us first ask a simple question: what determines a person’s gender? Is the person male or female? This is entirely defined by the X or the Y chromosome. You might have heard about this. Having an X chromosome and a Y chromosome means you are male, a man. If you have two X chromosomes, you are female, a girl.
Let us look at a couple who together have a child. The man has an X and a Y because he is a man. The woman has two X chromosomes. When they have a child, they will quite by chance pass on one of the two. So, the man can pass on the X chromosome and from the mother the baby will get also an X chromosome. With two X chromosomes, it is a girl. If the man produces a sperm that has Y chromosomes, so there is a fifty fifty chance, then the baby will get one Y from the father and one X from the mother and it will be a boy. Again, X and X will be a girl and X and Y will be a boy. Now, what really defines if it is a boy or a girl is the chromosome that the father passes on. Remember, in the middle ages, kings often blame their wives for not giving them sons. It is really the sperm of the king or the father which was the cause. Really, just by knowing which of the chromosomes have been passed on, we know if it is a girl or a boy.
This is the basic mode of inheritance and this is also how it works with other genetic traits and diseases. If we look at the factor-V gene on chromosome one, as I said, you get one chromosome with the gene from your mother and one from your father. Now, I need to teach you some technical words.
Section 4: Co-dominant inheritance
There is co-dominant inheritance. It means if you get one genetic defect in one gene, you have an increased risk. If you get two of this genetic defect, you have more risk. So, the more genetic variations you have, the higher your risk is. It is a kind of a logical deduction. Let us look at two people. Both have two copies of the chromosome. So, the factor-V gene on chromosome one. The woman is going to have two, one from the mother and one from the father. The man is going to have the same.
Now, let us mutate one of these genes in each of those people. We know from scientific studies if one of the two genes is broken, then you have an 8 times risk of developing thrombosis compared to people with no broken genes. Again, just like we have seen with the X and Y chromosomes, they are going to pass on one chromosome by chance. So, in case it is the healthy chromosome or gene that is passed on, this child will then have the normal risk of thrombosis. In case the baby inherited one broken gene from the mother and one working gene from the father, it is just the same like the parents, the risk is times 8. Here again, the risk is times 8.
This baby is unlucky. He inherited a broken gene from both parents. Here, it is actually not 2x8, 16 fold, but 80 fold. Really having more risk, it together multiplies by each other. So, it is not really additive but multiplicative. By having two parents who have 8 fold risk of developing thrombosis, you can get anything from no risk to 80 fold, 10 times higher than the parents. As I said, this co-dominant inheritance. The more genetic defects and variations you have, the higher your risk is.
Now, the question if you say why do a genetic test, let us just look at my family history? If you assume you are the same as your parents, this baby might have made the wrong conclusion. It has 8 fold lower risk than its parents. Those two will be correct. They have the same risk of their parents. This child has 10 times higher risk. So, really by assuming you are the same as your parents, you have a 50 % error rate. So, how can we really find out? You can test the gene. Then, we can find out whether you inherited any of it, maybe more of it than your parents and then you get more detailed information. So, this is co-dominant inheritance. The more genetic variations you have, the more risk you have.
Section 5: Recessive inheritance
There is something else called recessive inheritance. This means you need two broken genes for this disease to occur. Let us look at another example. Again, we have two people who have two copies of the lactase gene. The one that digests lactose. The one for lactose intolerance. Now, let us make two of these genes lactose intolerant, mutated. What happens is that if you have one gene that does not know how to digest lactose but the other one can, it is enough for the body to know how to digest lactose because this gene can take over the function of both.
So, really people, carriers we call them, who have one genetic variation that disables it and the other one works are lactose tolerant. They can drink milk. This person can drink milk and has no problems. Again, the father gives them one defective gene and a functional one. Then, this person is also not lactose intolerant. Now, they have children together. By chance, they pass on one of the two of the genes. This child has received two healthy genes. This child has received one mutated gene but from the other parent. So, these are carriers but they do not exhibit lactose intolerance. However, the fourth child has received two broken genes and both of them do not know how to digest lactose. So, this child is going to be lactose intolerant.
Again, when looking at the family history, why do a genetic test. Just I look at whether my parents are lactose intolerant, if the answer is no, then saying you are not going to be lactose intolerant is incorrect because this child is lactose intolerant. He has it from his parents’ genes, but the child could not see it in the family history. This is recessive inheritance. Again, a genetic test is going to tell you. Family history is not going to tell you. So, we have co-dominant where the more genetic variations, the more risk. Recessive where you need two broken genes for the disease to occur.
Section 6: Dominant inheritance
Then, there is dominant inheritance, which means one of them is enough to give you full risk. Again, let us look at a gene of which very parent has two copies; the HLA-B 27 gene. It is a genetic variation that increases the risk of the Bechterew's disease, which is basically a bone disease where the vertebral column begins to fuse together. So, instead of having flexible vertebral discs, it becomes one solid bone and then people start to have posture problems. They cannot move the spine anymore. This is very strongly influenced by genetic variations. Now, let us give both of these people this genetic variation. They have 78 fold risk of developing the disease and more than 95 % of all people who have the disease have this genetic variation. Both of them have high risk. By chance, they pass on one of the chromosomes and this child is going to be healthy. Even though both parents have a high risk, this child has no risk. If one of them is passed on, there is 78 fold risk as you would expect.
However, if you get two of the genetic variations, there is the same risk again. So, really having more of the same genetic mutation does not increase your risk higher. This is dominant inheritance. So, one genetic variation is enough for you to get the full risk. Again, you get 25 % error rate when you look at family history compared to a genetic test.
This is the end of chapter 15, how genes are inherited.