Genomics and Human Medicine - Online Tutor, Practice Problems & Exam Prep

The Human Genome Project revealed that only 2% of the human genome consists of protein-coding regions, while 98% comprises non-coding elements, including introns and transposons. Key variations among individuals arise from copy number variations and single nucleotide polymorphisms (SNPs). Transgenic organisms, created by introducing foreign DNA, are vital for studying gene functions and diseases. Gene therapy aims to correct mutations using viral vectors or liposomes to deliver healthy genes, exemplified in treatments for conditions like cystic fibrosis, enhancing personalized medicine approaches.

Human Genome Composition

Hi. In this video, we're going to be talking about the human genome and medicine. So, the Human Genome Project was the first major scientific undertaking to sequence the first human genome. And this is super important because without this sequence, we'd have really no idea how many genes we have, and therefore, we can't do anything to determine whether gene mutations are causing disease. So sequencing the human genome is really the very foundation for a lot of the gene therapies and the personalized medicine that you're hearing about today. And so the Human Genome Project's main function was to identify what was in the human genome. So what were the major components of the human genome? And what they found was actually extremely surprising.

They were expecting the majority of the genome to be made up of protein-coding regions, regions that had genes that produced proteins. But instead, what they found is that those regions actually only composed 2% of the genome, meaning 98%, so the overwhelming majority of the human genome does not encode genes, and that was really surprising to the scientists who were doing it. Now, that doesn't mean that there are a small number of genes. Instead, there are about 20,000 to 25,000, depending on the textbook you're using. We'll say either number, but it's about 20 to 25k genes. Now, each gene, though, can produce more than one protein. Right? So we have protein isoforms that are made through alternative splicing. And so, although it's 20 to 25 different genes, it can produce a lot more proteins than 20 to 25k. But still, the overarching concept I want you to grasp here is that the majority of our genome is not composed of genes but is instead composed of other things. And we'll talk a little bit about those things in a second.

Now, that means the next question was, "Well, are the genes equally distributed or are there clusters of genes found throughout the genome?" And they actually found that there are gene-rich regions, which are concentrated areas of genes, and then gene deserts, which are regions without any genes. And that was another interesting finding. And then finally, comparing individuals, there's about a 99% similarity between individuals. And we know our genomes aren't perfectly identical because if they were, we would all look exactly the same, and we don't. So there are 2 major concepts that allow for the genome to be different between individuals.

So the first one is copy number variations. These are variations in the number of gene copies. So either the gene has been deleted, or it's actually been inserted. Copy number variance is actually a big source of variation between identical twins because these copy number variations can occur very early in development. And so, even though identical twins have mostly identical genomes, they actually can have differences, and a major difference is copy number variation. And so if it differs between twins, then you can imagine how much it differs between me and you; it's a lot.

Then the second type is single nucleotide polymorphisms, short is SNP. These are single nucleotide variations between individuals, so between me and you. And there are actually thousands of these, if not even more than that, that exist between me and you. There's a major sort of variation in the human genome.

Now, if we look at the human genome composition, you can see that the protein-coding regions here are this dark green area, proteins, and you can see that it's very small and that the overwhelming majority of the entire human genome is made up of other things. And so these are things like transposons, which we've either seen a video about or will see a video about in the future, depending on the order of your textbook. These are kinds of jumping genes that jump around the genome. We have introns, which make up a huge portion. These are non-coding regions between the exons of the protein-coding genes. These are again transposons as well. We have duplication and heterochromatin here. So these would be gene deserts, right, because heterochromatin is not going to be expressed, these genes aren't going to be expressed. And then this whole 12% unique sequences, which is an interesting category that can include a lot of things, some of which is still unknown to this day. And so obviously, the human genome is this diverse selection of different molecules that do things other than just encode for proteins.

Now, the important part of the human genome that the Human Genome Project really discovered, and that was a shock at the time, was that these non-coding regions of the genome are just as important as the coding regions. The coding regions are only 2%. Right? So 98% are these non-coding regions, and therefore, they're extremely important. And so there have been a few different projects that have attempted to classify these since the Human Genome Project. One of these is called the ENCODE Project. It stands for the Encyclopedia of DNA Elements. And the ENCODE project is looking for enhancers, promoters, and pretty much anything that would be a regulatory region in the genome. And so this is a huge undertaking because if we can understand how the genes are regulated, then we may be able to understand what's going wrong in diseased cases. And then, another thing is that there are actually a big component of the genome is pseudogenes. So these are sequences that were genes. They were genes at some time; they resemble genes in a lot of different ways, but they are non-functional or inactive now. That could be due to some type of mutation or insertion or transposon. There are a lot of different ways that these genes may be inactive now or a viral genome insertion. Like I said, lots of different ways, but essentially, they were genes, and when you look at this genome, they're like, oh, that looks like a gene, but it's not quite because it's not functional anymore. So, with that, let's now turn the page.

Transgenic Organisms and Gene Therapy

Okay. So now, let's talk about transgenic organisms, and then we'll turn the page and go to gene therapy. So, first is transgenic organisms. Transgenic organisms are used to study human genes. So, what is a transgenic? Well, a transgenic organism is an organism that contains foreign DNA. Typically, this is done in a laboratory setting where scientists take a gene from one organism and put it into another organism. And we're referring to crops like rice and wheat, these genetically modified organisms that create a lot of controversy. But really, all they are is they are just a plant that contains a gene from another organism. There are a couple of different ways they could be created. We have gene addition, which is when some type of gene is added. And then we have gene knock-in, which is where the gene is added, but it's added to a specific site. Gene addition is actually fairly simple; there are a lot of very easy ways to get a gene into a genome. But gene knock-in is actually much harder because you want it in a specific site. Gene addition doesn't necessarily mean that gene will be expressed, but gene knock-in, you're putting it in a specific situation with a specific promoter, and it's going to be in there. Examples of these are the wonderfully colored fish you can buy at the supermarket or at a pet store. Those glow fish that glow. Well, these fish are just normal fish, but what they contain is they contain a gene from a jellyfish that allows them to glow those bright colors that you see in the grocery or that you see in these pet stores. So that's gene addition. But, you can also create different transgenic organisms by knocking out genes because they don't contain the correct number of genes. So, you have gene knockout, where the gene is entirely removed or silenced, but you can also do gene replacement, where you are removing one gene, but then you're adding a gene back in. And so, this is an example of how gene replacement or removal of a gene can result in a transgenic organism. And, like I said before, these methods create these genetically modified organisms, the GMOs, that we hear about so often in the news and see those anti-GMO labels on certain organic foods. But essentially, that's all it is. They are just plants or animals that contain a gene that wouldn't normally be there otherwise. And, some examples of this are that scientists can create mice that have a specific disease because they now have that gene, the mutated gene, for instance, that's creating that disease. And that way, we can use mice to study that disease instead of having to study it in humans. But then, probably the way we're most familiar with this is through crops or through food. And so, one way that agriculture uses this is by providing different crops with genes that make them resistant to pests. And so, transgenic organisms. So here's an example of a mouse with a transgenic organism. Here we have otherwise genetically identical mice, but with the exception of the brown mouse is a knockout mouse, and it's missing the gene for hair growth. And therefore, it looks like this little brown mouse, or the black mouse that's very genetically similar, almost identical, looks very different from it.

Now, gene therapy. Human gene therapy uses these transgenes, this foreign DNA, to treat or potentially, if possible, cure a disease. And the buzzword that we hear all the time in the news is going to be personalized genomics or personalized medicine. Essentially, what this is is when you have a disease and the doctors are unsure about what's causing it, what they can do is they actually can sequence the diseased individual's DNA. And what they're looking for is they're looking for a mutated gene. And when they find that mutant gene, what they want to do is they want to use gene therapy to see if they can correct it or overcome that mutation in a certain way. So generally, what this involves, you have some type of mutated gene. Right? And it's not working properly. Well, gene therapy wants to give the diseased individual the correct version of that gene, the unmutated version of that gene or that protein so that the body can create it and it can do something. And, there are two major ways that this is currently done. The first actually uses viruses, and it could even use viruses like HIV, which sounds a little scary. But essentially, these viruses have been stripped of their normal DNA. So all they are is this protein capsid, and that protein capsid is what gets them into cells. So what the scientists do is they take something like HIV, they take out the DNA, and that DNA is what makes it HIV. Right? It's what makes it do all the things it needs to do. So if it takes out that DNA and all you're left with is the protein capsid, then pretty much all you have is this, like, robot, essentially, robot virus that can get into cells, and it'll infect, but it'll inject whatever you want to. So, scientists take that protein capsid, and then they put in their own genes. And so, this means that this virus can't replicate, it can't make more HIV, so it's not dangerous. But, what it can do is it can carry a correct version of a gene into a cell. And so, when it gets there and it infects, it gives the cell that good gene. And then the cell has that good gene. It incorporates it into its own genome, and then can produce it. And so, then it will make the mutated version and the correct version, and the cell can use the correct version. And so, I'll show you an image of what that looks like in a second. But, there are also non-viral methods. And, these include using these things called liposomes. But essentially, they're just like vesicles, little tiny vesicle compartments, encapsulated by lipids. And they also just contain the gene of interest inside of them. Right in the middle. And, you can give these to diseased patients. They'll go into, for instance, the lungs, which is an example of how this is used. And, give that DNA to the lung cells, and those lung cells will create that protein and hopefully will attenuate some of the disease symptoms or potentially even treat or cure the disease. Like I said, I used the example of lungs. I did that for a reason because gene therapy is used for diseases like cystic fibrosis, which have a lot of symptoms with a lot of lung symptoms. And so if they can sort of, inhale that virus or inhale those liposomes, they get into the lungs, and they give those lung cells the correct gene, which is CFTR. That's the mutated gene in cystic fibrosis. You don't need to necessarily know this, but I'm just giving it to you in case you're interested. So they normally have a mutated one, and that virus can get in there and give them the healthy one, then the cells can make that healthy protein and overcome, at least for a little while, some of the symptoms of Cystic Fibrosis. So here's an example of gene therapy using, in this case, adenovirus as an example. So here we have DNA. So this is the viral DNA that allows it to get in, and this is the new gene that we're putting in here. So this would be the gene that would treat the disease. And we create these viruses, where we have adenovirus here and inside is this. So it contains our new gene. Then we say, okay, your virus, do what you do best, infect cells. And so that's what they do. They encounter cells, they infect, they get in, keep going in, and eventually, they make their way to the nucleus where they just deposit the gene of interest into the nucleus. And then that gene will be transcribed, translated, produced into a protein, which will hopefully treat the disease that you wanted to treat. So in some way, this is an example of creating this, like, transgenic organism, with the exception of the fact that, normally, these genes that are put in there aren't foreign DNA, but instead, just sort of the correct version of the mutated gene itself. So that's gene therapy. It's the coolest thing in the world, I think, that we can just give humans these genes, and hope that that will solve some of their disease problems. So, with that, let's now move on.

The human genome project discovered that protein coding regions make up what percent of the human genome?

• A. 1%
• B. 2%
• C. 10%
• D. 90%

Transgenic organisms are organisms that contain what?

• A. DNA from another organism
• B. RNA from another organism
• C. Protein from another organism

The purpose of human gene therapy is to what?

• A. Remove a mutated gene
• B. Remove a mutated RNA
• C. Remove a mutated protein
• D. Add a normal-functioning gene into the organism

Here’s what students ask on this topic:

What was the significance of the Human Genome Project in medicine?

The Human Genome Project (HGP) was a groundbreaking scientific endeavor that sequenced the entire human genome. Its significance in medicine is profound. By identifying the complete set of human genes, the HGP laid the foundation for understanding genetic contributions to diseases. This knowledge enables the development of gene therapies and personalized medicine, where treatments can be tailored to an individual's genetic makeup. The HGP also revealed that only 2% of the genome codes for proteins, with the remaining 98% consisting of non-coding regions that play crucial regulatory roles. This discovery has spurred further research into these non-coding elements, enhancing our understanding of gene regulation and its implications for health and disease.

How do transgenic organisms contribute to medical research?

Transgenic organisms, which contain foreign DNA, are invaluable tools in medical research. By introducing specific genes into these organisms, scientists can study the functions and effects of those genes in a controlled environment. For example, transgenic mice can be engineered to carry human disease genes, allowing researchers to investigate disease mechanisms and test potential treatments without experimenting on humans. This approach accelerates the development of new therapies and enhances our understanding of genetic diseases. Additionally, transgenic plants and animals can be used to produce pharmaceuticals, such as insulin, in a cost-effective and scalable manner.

What are the main types of genetic variations between individuals?

The main types of genetic variations between individuals are copy number variations (CNVs) and single nucleotide polymorphisms (SNPs). CNVs involve differences in the number of copies of a particular gene, which can result from gene deletions or insertions. These variations can significantly impact gene expression and function. SNPs, on the other hand, are single nucleotide changes in the DNA sequence. While most SNPs are benign, some can affect gene function and contribute to disease susceptibility. Together, CNVs and SNPs account for much of the genetic diversity observed among individuals, influencing traits and disease risks.

How does gene therapy work to treat genetic diseases?

Gene therapy aims to treat genetic diseases by introducing a correct version of a mutated gene into a patient's cells. This can be achieved using viral vectors or non-viral methods like liposomes. Viral vectors, such as modified HIV or adenoviruses, are engineered to carry the therapeutic gene and deliver it into the target cells. Once inside, the gene is incorporated into the cell's genome, allowing it to produce the correct protein and potentially alleviate disease symptoms. Non-viral methods use lipid-based vesicles to encapsulate and deliver the gene. Gene therapy holds promise for treating conditions like cystic fibrosis and other genetic disorders.

What are the non-coding regions of the human genome, and why are they important?

The non-coding regions of the human genome, which make up 98% of the genome, include introns, transposons, regulatory elements, and pseudogenes. Although they do not code for proteins, these regions play crucial roles in gene regulation and genome stability. Introns are non-coding sequences within genes that are removed during RNA splicing. Transposons are mobile genetic elements that can move within the genome, potentially affecting gene function. Regulatory elements, such as enhancers and promoters, control gene expression. Pseudogenes are former genes that have lost their function. Understanding these non-coding regions is essential for comprehending the complexity of gene regulation and its impact on health and disease.