Hi and welcome to lecture three of Genetics in Society. Today we're going to talk about genomics in medicine. We're going to touch on several subjects today such as how we can apply genomics to medicine. What a single nucleotide polymorphism is. How we use single nucleotide polymorphisms in gene association studies. The concept of the individualized genome and once we have disorder, correlated with a particular snip in the genome using those for diagnositcs for disorder. And we're going to end today's lecture with some information about gene therapy. So, first of all, let's consider what genomics can do for medicine. Well, the first major thing that genomics can do for medicine. Is, using, the genome information as a diagnostic for the probability of, of coming down with a partic-, particular genetic disorder. once you have a human genome. And you know where the genes are for a particular disorder. Then you can dissect that disorder down to its genes. And perhaps bisect the cause of the disorder. The ultimate molecular cause of the disorder. Once you have the gene sequences and you compare a non functional gene or a aborrent gene with a working gene you can now start to think about of using that working gene as a gene therapy. And then w-, what we can do also is associate genes with, genetic disorders using genome-wide association studies. The first step in any human genomic study is to obtain DNA sequences from individuals. And in the example on the slide, we have several individuals Who would offer up a sample of DNA. That sample of DNA would then be sequenced using the methods that we talked about in the first lecture. And once you've sequenced the genes then you can start to look at the sequences to see if there are any changes in sequences from one individual to the next. So in this example, we have three kinds of, of sequences. Blue, green, and purple. Now, when a sequence varies from one individual to another, we call that a polymorphism. And in this particular case, the blue individuals all have a g in this position. And so they're polymorphic at that position relative to the other individuals. In addition, there are a couple of places where there are single base change, changes in single individuals. These are also polymorphisms, and they become useful in more high-powered human genome studies. [INAUDIBLE] these, this particular region, with the g, can now be focused on as a single nucleotide polymorphism, or a snip for further analysis. And attempts to correlate that snip with genetic disorders. So the basic structure of a, of a genome wide association study. Is to obtain a group of individuals with the disorder and a group of individuals without a disorder and to sequence their genomes. And once you have their genomes sequence you can look for correlation of snips in the population of individual with the disorder relative to the population without the disorder. Obviously, any snip that's, say, a G in all of the individuals with the disorder and an A in all the individuals without the disorder, that snip, that G snip becomes very, very important in understanding that disorder. The genome-wide association studies take advantage of a database called HapMap and HapMap therefore becomes an important tool in how we do human genomics. In this slide, we see 13 human chromosomes, and they're colored dots are disorders that have been mapped to a particular region of those chromosomes. This particular region of, of the, of that chromosome has four genetic disorders that can be mapped to that particular region of the chromosome or to that particular set of snips on the chromosome. Now, this kind of genome association studies requires that you Cluster people of geographic origin together. Or cluster people with genetic disorders together. A more efficient to do things that's arisen recently as a result of the lowering of cost of, of sequencing a human genome is to do individualized genomics. >> In this approach the genomes of, of, of an individual who's afflicted with a disorder. And members of his or her family are sequenced. And this allows for researchers, then, to scan the genome sequences that are obtained in an individualized genomics. >> And to correlate changes in the individual afflicted with the disorder with a particular snip in the genome. This is an approach that's going to become more and more popular as a result of, of lowering of the cost of DNA sequencing. And it won't be surprising to most people to learn that we will. Probably be carrying our genomes around in our wallets sooner or later. As I said, once you correlate a snip with a genetic disorder, you can then use that snip as a diagnostic for that disorder. And so for instance there are thousands of genetic tests that can be done today. That are, are available from testing, laboratories all across the United States. That allow for the diagnosis of genetic disorders. Disorders such as Lou Gehrig's Disease liver disease, cystic fibrosis, muscular dystrophy. thousands, literally thousands of, of genetic tests that can be done. One of the other applications of, of having a, a human genome sequence is that we, we'll know where disease, loci are but we will also have gene sequences that can correct those disorders. And the trick with this particular way of thinking about medicine is to get the, the, the, gene that doesn't cause a disorder into the genome of a person where the disorder exists as a result of a genetic, mutation And this is called gene therapy. And in, in gene therapy. What you do is you, engineer an adenovirus. Adenovirus is a, simply a virus that infects human cells, but doesn't cause us to get sick. You then allow that adenovrius to infect. The cells of the individual who who you're trying to do the therapy on. And then that gets into the cell and, and then the DNA that corrects the disorder gets incorporated into the genome of the, of the individual with the disorder. Gene therapy has had somewhat of a checkered past. In the early 2000s several gene therapy experiments were done, and some ended tragically. however, more recently, gene therapy has been used in two very important studies. One as a, as a cure for Hemophilia. B, Hemophilia B is a, is a blood clotting disorder, where the Hemophilia B gene, protein is missing, in the clotting cascade. The identifier method has been used to replace the identify, the hemophilia B gene in individuals who have are afflicted with this disorder. And they have recovered from this disorder. A year later, in 2012, researchers announced that a retroviral -based delivery system of genes to T cells allowed for T-Cells to correct themselves with respect to HIV. In this particular method, the retrovirus which is simply a piece of DNA that can insert itself into the genomes of, of individuals was, was engineered with sequences that allow the T cells of HIV-infected people to function correctly. and in this particular paper researchers have shown that patients treated with this method Have stable, T-cells for, over a decade. Sequencing genomes, and the human genome specifically, has become an important way to do modern medicine. Once we have genome sequences, we can correlate those -- we can correlate variation in the genome sequences Snips, single nucleotide polymorphisms, to disorders. And once that's done, we can use those as diagnostics for whether or not a person will develop that disorder. We can also use the snips in human genome sequences to understand the genetic basis of disorders. In other words, to use them to dissect the genes that are involved in particular disorders. And, finally, we can use, the genomic information as a way to, correct genetic disorders through gene therapy. What this means is that genome sequencing, especially in humans, is going to become a very, very important part of modern medicine.
