What are genes?
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What are genes and what information do we get from genetic analyses?
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Section 1: Intro
Chapter 13. What are genes and what kind of information can we get from genetic analyses? In this chapter, I want to explain generally what genes are, what influence they have on our body in terms of health, lifestyle, body weight and fatty performance and so on. I want to differentiate between different kinds of genetic tests because they are not all the same. There are different kinds of tests that have different aims and different roles. It is important to start having an overview of what kind of genetic tests they are and what kind of tests that we perform. So, let us first start with the question: what are genes?
Section 2: Genes
The human body consists of around fifty billion cells. Every cell, with some exception like blood cells for example, has a cell nucleus. The cell nucleus contains chromosomes. These latter are the x shapes that you see here. If you take a closer look at a chromosome, you see it is a very tightly round thread. This thread is the DNA double helix and that is where we have the genetic code. In other words, it is the blueprint of the body. It is really the information on how the body needs to be built. Geneticists like to represent these genetic bases, which are basically chemical structures in letters.
We call them A T G and C. They are just short forms for chemical words. If you just stick with A T G and C, then this is the genetic code that we work with. Here we see one strand. Now, we come to the genes. A gene is a certain region in here that has a certain function. For example, there is a gene, the pigment gene, which means that this genetic code region has the information of how to create a pigment, a color, that is then expressed in blue eyes for example. So, a gene is really an instruction in a genetic code which tells the body how to do one or only a few processes. The problem is that most of us have errors in these genes, genetic variations or real errors that completely destroy the function of the gene. These are called mutations, if they are rare or genetic variations if they are more common.
Here is an example. I have three genes; one of them is a coagulation gene, factor five. This gene inhibits blood clot formation in the blood stream because you do want the wound to close up through blood clotting if you cut yourself, but you do not want this to happen in the blood vessels. Then, there is an enzyme gene. An enzyme is a small gene like scissors that break up things or put things together. In this case, this enzyme gene is called lactase, which necessary to break down or digest milk sugar lactose. Then, there is the bone formation gene. It is basically one of the components for strong bones. The Col1A1 to have strong bones. Now, let us introduce a mutation in genes. Here you see the letter change. In the coagulation gene, this genetic variation happens; the instruction is disrupted. The gene no longer inhibits blood clot formation and it can lead to thrombosis, i.e. blood clot forms and blocks up blood supply to one part of the body. If the enzyme gene is defective, then the body does not know how to digest lactose. It forms lactose intolerance, one of the most common forms of food intolerances. For bone formation, instead of building strong bones, you build bones that lose their density faster with age and this leads to osteoporosis. So, really a small letter change in our three billion-letter genetic code can cause a severe disease. It is just one letter.
You have to consider that every human being has three point two billion letters, A G C T G. If I continue reading in this same speed, I would take one hundred years just to read out the genetic code contained in one cell. It takes ages because there is so much information. Just one specific letter change can cause such a disease. These are some quite severe examples, thrombosis, lactose intolerance and osteoporosis. It is estimated that every one of us has around two thousand genetic defects, or more correctly said genetic variations, that influence our body in a negative way. They are not all as severe as causing life threatening diseases but they can make our eye sight a little weaker or they can reduce the effectiveness of our immune system or make our legs shorter or longer and so on. Really, there is a multitude of negative genetic variations that can influence our body and every one of us has a different combination, which is really why every one of us has other genetic talents as well as risks for diseases.
So, the question is: how do we get these mutations? There are a number of ways. One is radioactivity. Radioactive radiation can hit the DNA strand and can break the code. Then, you actually get a letter change in there. Then, there is UV radiation. UV radiation from the sun for example hits our skin and then it can hit a gene or a genetic code and make it change. This is why we can get skin cancer from too much sun exposure. Soot or smoke are chemicals. When they reach our body can grab onto DNA and break it. Then, there are copying errors. You have to consider when an embryo is created, you have an egg and a sperm. Each one of them contains half of the genetic code that a cell would have. They fuse together, then they have one full set of frequent two billion letters. For the organism to grow, you need more cells. Therefore, you need to copy the whole thing once to create two cells. So, copy three point two billion letters, you get two, copy them again you get four, copy them again you get eight. Really, to create fifty billion cells, you need to copy the DNA a lot. This is surprisingly error-free, but nevertheless from one generation to the next, you end up with around three genes per generation.
If you look at my parents and me, I will have a mixture of genes from my parents, but there will be in average three changes that will be different in me compared to my parents. So, copying errors is also one of the sources. There is one more thing I want to say here. While radioactivity is absolutely a cause of genetic mutations, it is not usually as severe as copying errors because radioactive rays or UV radiation hit my cell in my skin and it hits by chance my lactase gene. So, my skin cell loses the information of how to digest lactose. It does not really matter to my skin cell because my intestine needs to know how to lactose. Really, these kind of mutations happen in individual cells. They do not usually have an impact on a person’s health. The only exception is cancer. We have anti-cancer genes. When these are disrupted in one cell, then this cell starts to grow uncontrollably. Therefore, one cell becomes two or four and it grows into a tumor. This is a rare thing to happen.
The genetic variations that really do influence our health severely are the ones inherited from our parents because they are in the first cell and this cell becomes two, four or eight and every cell in my body is going to have this genetic variation. So our health is mostly influenced by genetic variations that have originated some time ago in our human history, forty thousand years ago, one million years ago. These variations now influence our health negatively.
Section 3: Mutations and genetic tests
Ok. Now, let us look at few different genes and let us have a look at what mutations can do to our body. As I said, there is a coagulation gene, factor five, which prevents blood clot formation. The lactase gene, which splits lactose in our intestine. There is a renal tissue gene called Col4A5, which builds strong kidney tissue. The kidney can work and remove toxins from the body. Then, there is a fat-intake gene, which regulates how much fat we absorb from food. When you eat something with fat in it, it absorbs it. It regulates how much of it. There is also an iron-intake gene, which absorbs iron from our food.
So, there is one gene which has one or few functions and all of these together build the blueprint of our body. Now, if we look at the renal tissue gene that I use as an example. As I said, it builds string kidney tissue. Let us say through a copying error, it happened that the genetic code has changed. This happened by chance, just a copying error, there is nothing deliberate and it happened outside the gene. This will usually not have any influence. There are millions of these variations in every person’s genome that do not have any impact on it because they are in, let us say, a genetic chunk in-between the genes that are the important parts. The other parts have also some importance but most of these variations have no impact on a person’s health.
However, if one of these mutations happens within the gene, it can disrupt the function. Then, we lose the information of how to build strong kidney tissue. In the case of this gene, Col4A5, the person will have progressive renal failure. The kidneys start to fail. A doctor will see progressive renal failure in a young person and he would ask why this is happening? If he knows enough about genetics, he will know that it might be a disease. He will do a genetic test for the Col4A5 gene. Then, you will usually read out the whole genetic code of this gene. It is a very big analysis. You need to do tests for several thousands of genetic letters and then compare them to what we know to be a healthy code.
This kind of analysis is usually quite expensive. It is in the range of one thousand and five hundred euros to test one gene. In the end, you will get a report saying yes we have found a mutation in this gene. This indicates that there is the Alport Sydrome disease. Then, you have to run a diagnosis to know the reason for this renal failure. This disease, just as an example, is very rare. Only one in fifty thousand people has it. So, does it really make sense to test this gene in every person? Unlikely because you are going to have one positive result in fifty thousand and forty thousand and nine hundred and ninety nine are negative results. These kinds of genetic tests are what people usually consider to be genetic tests. It is a rare disease, you need a diagnosis; you do not know why this is happening. Then, you do a genetic test. Then, you confirm it through finding a mutation in this gene and then you know this mutation causes this disease. It is a diagnostic effect.
For example, this disease is not treatable. It is just finding out about why this is happening. This is the normal type of genetic tests that people consider to be genetic tests. They are rare diseases. There are six thousands different genetic diseases that are known. There are genetic tests for three thousands of these. We do have them in our portfolio, but these are actually the less interesting ones because they are really diagnosis. You find out what is wrong and usually you do not get any specific treatment or prevention from these kind of genetic tests. They are just diagnostic. Then, there are genetic variations for common diseases.
Section 4: Polymorphisms
Now, I need to explain a term called polymorphisms. If you take the genetic code of a person and lay it down in one line. As I said, there are three point two billion letters and that is where the genes sit. Around thirty thousand genes are lined in this genetic code. If you then take another person, maybe a relative. You take this person’s genes or DNA and put them next to each other, we will find that they are almost identical. You will find the same gene at the same location. Both have the same genetic code in genes. You will only find a change in average one in one thousands genetic letters. They are almost the same, you only have a few variations. These are called polymorphisms.
The difference between polymorphisms and mutations is that polymorphisms are common, found in many people. Mutations are uncommon. They hit one individual or one family. They mean the same thing, it is only a different terminology that we use. So, if we look at these polymorphisms here, this is where the genetic code will be different between two different people. Most of them will be somewhere in that genetic area, which has no important function. Some of them will be in genes. These variations, as I said, are quite common and there is one difference in one thousand bases, which is actually surprising. If we take the DNA from a chimpanzee and you put them next to each other.
Again, it is very similar. The genes are usually in the same locations but you will have one difference in one hundred bases. It is really surprising. We have the same evolutionary history, and we can still see that in our genes. Alright. Most of these genetic variations do not matter. Sometimes, they disrupt a gene and have a function. This is something you will have to remember. They are called Single Nucleotide Polymorphisms, single letter changes. There is a term that scientists use. The short term is S N P. however, scientists like to use the term SNIPS, to label this. So, when you hear about SNIPS, it is a very common term, it means the genetic variations indicating that one person has the letter A in one location and someone else has the letter C. They are very common. There are around ten million known polymorphisms in the human genome. When we look at people from different regions, they found ten million different variations.
The majority has no impact on health or body or anything. As I said, around two thousands of these polymorphisms negatively influence our health. Now, let us look at a common example. Lactose intolerance or tolerance is a very common example of a food intolerance. This is the inside of an intestine. When lactose is eaten with food, that is when milk or milk products are ingested, then it cannot be absorbed into the intestine. You first need a lactase gene. This gene has some information of how to build an enzyme, a kind of small scissors. This enzyme can then break lactose into smaller sugars. Lactose is a combination of two sugars that are bound together and the enzyme cuts them into pieces, glucose and galactose, small sugars. These sugars have the advantage of being absorbable. The body then can use these sugars as a source of energy. They are very important for babies because these are one of the energy sources that they get from the mother’s milk.
Nature is quite conservative with energy. In the Stone Age and usually mammals need to be able to digest milk for their babies who need milk from their mothers. It is crucial for survival. However, when they grow up, a grown up cow for example, do not ever drink milk again. A grown up Neanderthal or our ancestors do not drink milk anymore because they are used to not have cows or any sources of milk. So, nature decided to save the energy of building this enzyme if we do not need it. So, there is a genetic element, this here, which begins with increasing age to turn off the gene because it is no longer needed. The enzyme is not produced. This usually does not matter because the cow or the deer does not drink milk anymore when it grows up.
Now, humans started to raise cows and now we can drink milk when we are adults. Then, lactose is digested by bacteria because it is not taken up. Bacteria produces all sorts of acids and waste products that then cause severe digestive problems. This is what you see. The amount of lactase enzyme is usually high in the beginning and then it starts to decline over the years. Meaning that in one of six people, the lactase enzyme is gradually switched off and it will first cause mild symptoms. If you eat milk products, it becomes increasingly severe. There is a genetic variation that disables this switching-off function. This is a SNIP. It is a very common polymorphism that has developed and it is common among people of European ancestry. In this case, the enzyme is produced even with increasing age.
Then, the sugars can be taken up. Even grown-ups can drink milk if they have this genetic variation. It is not a variation that causes a disease, but actually something that was beneficial. This is what happens in these people. Five out of six people with European ancestry produce lactase enzyme constantly. They never show symptoms of lactose intolerance. The question is: if this is the variation, the mutation, the abnormal thing, why is it so common in European ancestry?
This is quite an interesting story. Between forty to ten thousand years ago, humans have already populated Europe. In the north of Europe, scientists estimate that around Sweden, this genetic variation occurred in one person. This was the first person as a grown-up who could drink milk without getting digestive problems than all the others around him. During that time, there was famine. So, there was not much food available, many people died. This person had an advantage because he already had animals from which he could get milk, but most of the others could not drink any. He could. He had such a big survival advantage in those times. His children had also this genetic variation. Their children again had this genetic variation. This person is a direct ancestor of eighty percent of people with European ancestry. So, this genetic variation hit one person. It was inherited to many other people.
Then, there was such a big advantage that really populated and repopulated Europe. This is one very common polymorphism as I said. Eighty percent have it. Twenty percent do not have it. Those twenty percent of European population became lactose intolerant. There is some more information about lactose intolerance in case you are interested in another training, but I am just giving you few examples. Another one is the Iron Overload Disorder. There is a gene which says I need iron from food. It absorbs iron but it says do not absorb too much because too much iron can be detrimental to health. A genetic variation in this gene can disrupt this process. Then, too much iron is absorbed. This is what happens. Iron is increasing in the blood over the years. In the beginning, there are no symptoms but then you start to develop joint pains. You get the susceptibility to infectors. The immune system gets weaker. You become diabetic. Eventually your liver is damaged and it is fatal if you do not obtain treatment.
Now, the doctor will usually find this is what happens. He will usually find at some point that these symptoms indicate hemochromatosis. It is a technical term for Iron Overload Disorder. Then, he will do a genetic test. This test will confirm there is a genetic variation. However, this is unfortunately still a rare occurrence because seventy six percent of diagnoses are wrong. We know it is diabetes, but the cause of it is really iron toxification. It is not diagnosed correctly. The doctor has done a genetic test and he knows. Then, he starts with a blood letting therapy. Blood contains a lot of iron from the hemoglobin, the red substance in the blood that transports oxygen. When you remove blood from the body, blood becomes new and uses up some iron. You can reduce iron content by a regular blood letting. If you continue this for the rest of your life, you can keep it in the normal range.
The problem is that the disease that has already developed will remain. Usually, life expectancy is severely reduced. This is a typical genetic test that is done to diagnose a disease. However, there is a way to use this information in a preventive manner because this genetic variation is present from birth, from the moment the embryo had been created by the fusion of the egg and the sperm. From that moment on, we already know that this person has this genetic trait. Now, using this exact same genetic test that has been done in hospitals worldwide before you can even detect elevated iron levels, you can find out that this person has this genetic variation. Then, you can start prevention. This is a very specific prevention because this person should go to blood donations. It is the same like letting therapy. You remove blood from your body. Your body uses up more iron to build up more blood. Then, you keep it in the normal range for the rest of your life. You help other people with your donations, but you also remain healthy. It is really the same genetic test. One time you do it to find out about what causes the problem. In another time, you use it to prevent the problem from occurring, preventive genetic medicine. This is one of the big focuses that we have. Then, we have rare diseases that only affect one in fifty thousand.
Section 5: Medication
We have common diseases that affect most of us. Then, we have medication. The way medication works in our body is also influenced by genetics. For example, drugs, like aspirin or some medication, only have side effects on around sixty percent of the population. It is more for some drugs, less for others. We know, they do not usually work the same in everyone. Some people have side effects, which can also de deadly, some people have no effects.
Statistics tells us one of twelve hospital patients suffer from severe side effects. They are for some problem but they really get another problem through the drugs that they are taking and one out of two hundred fifty dies due to these side effects. They really die, not because of the disease or the problem that they have, but from the treatment. It is the fifth most frequent cause of death in the western world. It is really one of the big problems that we have. Without medication, of course many more people would die, but many people would die because of drug side effects. There are certain genes which control how these drugs are converted into our body.
Let me show you an example. If you take a drug. For example you swallow a pill. The drug gets into your body and shows its effects. Then, the drug is recognized in the body as something that should not be there because these drugs are chemicals that should not be there according to the body. So, the liver has enzymes that recognize it, modify it and more or less tag it for removal from the body. This enzyme comes from an enzyme gene. The modified drug is recognized by the kidneys and then it is removed from the body. Then, what happens if you take a drug? It increases in blood level and then it goes down again. Here it is how it would look. It goes up and then it is slowly removed again. Then, you are in the effective dose of the drug for some time till you get less headache. Usually, a headache only lasts for few hours, so you are covering this very well with an active dose.
Now, there are some other drugs which should be in active range for a long time like antibiotics which it should take for a week. What you do is you take it in regular intervals. Whenever it would go high you take it again. Then, you always stay in the effective dose of the drug. Now, that is the normal way it should work. However, some people have genetic variations that disrupt the function of this enzyme gene. so, the drug is taken. It still has its effect, but the gene is not producing the enzyme. Then, what happens? The drug is not broken down, not modified. It is not removed from the body. It starts to accumulate if you take it several times a day. What really happens is you get more and more of the drug. Therefore, you go beyond the effective dose and you get severe side effects. One such example is a blood thinner. It is modified by one of these genes and a genetic variation can lead to uncontrollable bleeding as a side effect because the drug has such a high dose. So, drugs and how medication works are also influenced by genetics. We can do a genetic test. We can find out this drug should be reduced in dose, this should not be used and this one is ok.
Section 6: Obesity
Moving into a more life kind of area, body weight. Obesity is also controlled by genetics. Let me explain one example. This is again the inside of the intestine. This person had a fatty meal. The body recognizes there is fat in the intestine. That is great, let us absorb it because it has a lot of energy. We can use to create new cell roles and so on. The body starts absorbing it. It is then used up or stored somewhere. Then, there is a stage where a fat absorption gene says ok thank you we had enough. Then, it would stop the absorption. I have to say this is very simplified.
The process behind it is much more complicated, but the example demonstrates the mechanism behind it quite well. So, this gene says ok thank you we had enough. The rest of the fat stays in the intestine and then it is excreted from the body. There are some people who have a variation in this gene. It means that this gene does not work as it should do. Fat is absorbed. Then, the body gets all of it. The problem is the more fat you eat, very fatty food, the more you absorb. Some of it is used up and the rest is stored somewhere for more times in the future and that is the problem of obesity; too much fat stored. A genetic variation can influence how sensitive you are to the amount of fat you eat. There are brilliant scientific studies that have shown if you give a person twice as much fat to eat, some people would gain weight, as you would expect and some do not because they just do not absorb it. Then, body weight is modified by genetics. When a person wants to lose weight, the question is: should he go for low CARB diet, everybody has heard of this, or a low fat diet, the opposite? A balanced diet, a little bit of both. There are many different options. From genetics, we can find out if your body does not absorb fat as effectively. The fat stays in the intestine and low fat is not going to do much. The same thing goes for carbohydrates. Some people gain more weight from carbohydrates, others do not. We can really find out how your body is built, how much of each of these substances is absorbed. We can find out from a genetic test what is the most effective low fat/low carb are.
Section 7: Diet/nutrition
This is body weight. Next question is diet or nutrition. Everybody has heard about what is healthy to eat. You should eat many fruits, vegetables, low fat and so on. Everybody thinks that there is one way of how to eat healthy. However, this is not really true. Let me explain the concept of nutrigenetics, nutrition and genetics. It is a growing field. Let us look at three people each with a genetic disease. One is lactose intolerant. One is gluten intolerant who cannot digest wheat, he gets bad reaction from wheat, he cannot digest it. The other person has the iron overload disorder, he absorbs too much iron.
These three people listen to the general guideline of healthy diet. These say dairy products are healthy, they are good source of calcium. The lactose intolerant person will not agree. When he eats milk products, he will get severe side effects, he will feel very ill and very bad. This guideline really does not apply to him. The gluten intolerant person who has problems with wheat protein would say yes sure, it is a good source of calcium. It is healthy and tastes good. That is true. The person with the iron overload disorder also applies it. Then, wheat. Maybe a whole bread meal, where you have a lot of wheat protein, will not be a problem for the lactose intolerant person. For the gluten intolerant person, it is unhealthy. For the iron overload disorder person, again there is a lot of fiber, it is good for digestion. It is really healthy. Again this only applies to some people. Low fat red meat is a good source of iron. So, people who have an iron deficiency are advised to eat more red meat. It is true for lactose intolerant people. A good source of iron for gluten intolerant people. However, people who are already absorbing too much iron from diet should really not eat much red meat, but low iron content food.
So, these guidelines, as good as they can be, when you have to issue one guideline for everybody, but really every person is genetically different. He has different risks, different disease risks, different strengths and weaknesses. Therefore, one guideline for everybody is not possible, as you can see in these examples. Nutrigenetics does this. They look at what your genetic variations are and how to modify your nutrition to make sure you get the right nutrients, you avoid the wrong nutrients and you maintain optimal health. This is nutrigenetics. Some people say this is the stuff of the future. Twenty years ago maybe they were right. In the future, we are going to be much better than we are now. However, nutrigenetics is already present because every person who has lactose intolerance, that is twenty percent of Europe, is already avoiding lactose-containing food. So, this is nutrigenetics in action.
Section 8: Talent for competitive sports
Then, there is talent for competitive sports. Sport is really filtering for the right genes for optimal performance; athletics, competitive sports. Many people try to compete and only the ones who have the optimal combination of genes win. It is very easy to understand a pro basketball player or someone who wants to a be a pro basketball player who has short legs, genes make his legs short. He is not going to have much chance. There are some other variations that influence the structure of muscle cells.
Am I more towards power or endurance? There are two genes that influence us. For example, we can have two ENDURANCE genes, we can have one ENDURANCE gene and one POWER gene or two POWER genes. We know from scientific studies that if you have either of these variations of the genes, they are better for power, power is strength, quick reactions, sprinting, you have to really start quickly. However, they tire very quickly and if you want to run a marathon, it would be bad. What scientists did is they looked at these genes and looked into a control group, the general population that does not perform any sport and they found that fourteen percent have ENDURANCE genes, which are good for marathon running but they are bad for sprinting for example.
So, fourteen percent have bad genes for sprinting of the people who do sport. Then, they looked at pro sprinters, people who are at the Olympics or won championships in sprinting. They found that three percent of them have the wrong genes for sprinting. From the general population, many decide to become a pro sprinter. However, I select a group made out of these, mostly the ones with the right genes. It does not mean that it is impossible. Three percent of them have the wrong genes for the sport, but the chance in this case is five times worse to reach the Olympic level if you have the ENDURANCE genes. So, all of athletic performances and musical ears are genetically influenced.
So, genetic testing can tell really us anything from rare diseases, standard genetic tests, common diseases, medication, talent as well body weight and healthy nutrition. These are of all the different areas. They are classified into three different groups. One of them is lifestyle analyses. This is not really about diseases, it is about optimizing body weight. It is about sports. It is general information about the body that has nothing to do with diseases. Then, there is the medical analyses commonly used for preventive purposes but also for diagnostic purposes. Then, there are rare diseases, which are usually diagnostic in nature. Our laboratory network performs tests in all three categories. However, the interesting ones are medical analyses where you have preventive potential. We can help people stay healthy when you have a genetic risk. We can also optimize the treatment. Obviously, if you have a disease, you need effective treatment. Lifestyle analyses also help people to maintain their body weight.
Section 9: End
So, that is the end of chapter number thirteen. What are genes and what kind of information do we get from genetic analyses?