Transcript for:
Human Genome Features

If someone further. Everyone sees the screen well, everything, No? All calm down. You can see it well. Yes, I know well. Spectacular. Well, question. Let's go start then with the first part which is generalities of the genome. a We talked little when we saw biology and gene expression and more of the genome human and that, we are going to focus on to delve a little deeper into the different sequences that are apart from genes, eh because we already gave a lot of attention to what is a gene and how its expression is regulated of the genes. Let's see others non-genic sequences and then we'll see how DNA can mutate, right? AND and generating variability or variants of sequences. So, a little bit average introductory, which we have already discussed, The human genome can be defined as the material the material set genetic of an organism, right? Eh, or of a cell of an organism that includes both nuclear DNA in the case of human germ, right? Includes the DNA of the nucleus that is organized in chromosomes, right? In 46 chromosomes and the DNA that's in the mitochondria, right? We talked about that a bit. the mitochondria, which is this organelle that It is responsible for producing energy, eh, that We will see it in another class. go ahead, eh they have their own DNA to make their own proteins or some of them very little protein. Today we are going to focus more than anything on the genome nuclear, but know that the human genome It encapsulates what the nuclear genome is, chromosomes and mitochondrial genome, which is similar to bacterial DNA due to its characteristics. And the genome is not the set of genes, mind you, yes. The genome is all my DNA, which are genes in large part eh little ones and sequences that are not genes, which is the majority of sequences DNA that does not provide information for make a protein. Yes, sequences extragenic. So here we have it same, the DNA, the nucleus that we know that It is organized into chromosomes. Have 46 chromosomes, 23 pairs, right? And and every chromosome pair, of each pair chromosomal, I inherit a chromosome from my father and one of my mother's, No? So, we saw that we have more or less than 30,000 genes, of which more or less 21,000, 25,000 are the genes that They have information to make proteins. And we have a smaller group of genes that They are called genes that code for RNAs non-coding, that is, they code for functional products, for RNAs that They have a specific function, but They are not translated into proteins, right? As ribosomal RNAs, RNAs of transfer, microharnesses, are they remember? small RNAs in the nucleus that participated in splicing. So we saw that there are messenger harnesses that They code for proteins and there are kidneys that They have no information to do proteins and fulfill a function within of the cell, right? So this with the sequences that are genes, but we are going to Let's see now for a moment that genes are the minority of the human genome. Yes, to difference from what was previously believed, We know that humans have DNA nuclear cluster of achromosomes, such as I told you, okay? This is the chaos human, that is, the set of chromosomes which can be from an individual of a species. And the normal catatype consists of 46 chromosomes, right? Of which there are 22 pairs, right?, of chromosomes that are They are called autosomes or chromosomes autosomal, yes? and a sexual pair. Good, That is, we have 44 autosomes and two sex chromosomes, 46. And to make a writing of what we are seeing, the total number of is written chromosomes that we see, in this case normal, 46, and after a comma, the sixth chromosome that we see. In this case, this little photo, we see that a X chromosome and an I chromosome. This is a cayotype of a more individual eh chromosomally male, right? He Xi chromosomal sex, the Xi chromosomal sex is masculine, right? It could be XX the female. So the cardotype is this, the set of chromosomes, yes?, of a species. Eh, in humans there are 46. No. confuse autosomal chromosomes with somatic cells, eye, which are terms different and confusing. Now we are going to char when we go mutations the same, but eh sometimes they tend to confuse it, don't they? Okay, and as I told you, then we are a diploid species, which means that we have chromosomes that are apes. We have two complete sets of genetic information, two sets complete chromosomes. Yes, half of my DNA, half of my chromosomes, 23 chromosomes are inherited from the father, by the sperm. And the other 23 chromosomes are read by the maternal line my mother's obsession. I have the paternal chromosome one, paternal chromosome two, 3 4 5 6 22 autosomes and one chromosome sexual that can be either X or I. And the Mom also inherited chromosome one maternal 2 3 cub bla bla bla 22 and the sex chromosome that would always be of the mother the X. So, eh I'm 23 maternal chromosomes, 23 paternal put together they form the complete set of 46, Yeah? Eh, with homologous chromosomes, right? Chromosomes of the same pair as the same sequences, which are very identical. Dad's chromosome one and one from mom, two from dad and two from Mom, right? So when the event occurs fertilization, we say that it is restored in the diploidy of the cell. Is that is, we started to have ID cards with the half of DNA. When they fertilize, I have a cell back with 46 chromosomes. Yeah? This is what we have in all the cells in my body, except in the gametes, right? Good. So, a game complete set of chromosomes comes from wolf cells and another complete set of chromosomes comes from the foam cell. So, each sequence is repeated twice. As one of dad and one of Mom has the same sequences in the same positions. I for each sequence I have two variants, two versions, for example, of a gene. Those different versions, maternal and paternal, They're called alleles, aren't they? For example, for the gene for any of the P53 protein, No? That gene, I have the variant of gene that is on dad's chromosome and a copy on mom's chromosome, in the another chromosome of that pair, right? So, in each chromosome pair, yes, I have the same positions, same sequences. Each sequence, each gene is repeated twice. Yes I have two eaves. Well, so far we are doing well with this, mallet in general, yes? No, good. Any doubt. Oh, hi, I just saw the message. Everything is fine so that I don't get to see it. that I couldn't focus well. Hey, whatever they offer me. Yes, question. He We're going to measure DNA, okay? To measure the long size in base pairs. HE agree that DNA is this double propeller? If I unroll it I can see that are joined in pairs, right? I'm here I have, I don't know, see, cytosine, guanine, adenine, thymine, right? The bases complementary. I could measure this fictional, hypothetical sequence, how many more base pairs are long? as if they were the steps, the steps of a ladder. I measure here and I have 1 2 3 4 5 6 7 8 9 10 pairs of bases. So I say, this sequence DNA measures 10 base pairs, right? AND This is how the size of DNA is measured, of the genomes. Since DNA is so big, yeah? Units can be used relative. For example, when we arrive to count 1000 base pairs to above, thousands of base pairs, we are talking about kiloases. One kilo is 1000 base pairs. When we get to million and millions of base pairs, we talk about megas. A meggaase son 1 million little letters of pairs of bases. And if we count 1000 millions, we are talking about gigabases. Yeah? Eh, a gigabase is 1 billion letters. Human DNA has 3.2 billion base pairs or 3.2 GBes. Yes, it seems like a big number, but If we compare with other species we will see that it is not so much. Eh, and I'll tell you also that this size that is measured, the human genome, which measures 3.2 billion base pairs, it is by aploid genome. That is, taking into account only one chromosome of each pair. Yeah? And now let's see why. I tell of some chromosome of each pair and not the 46 chromosomes. Now I'll tell you why. So, human DNA is made some estimates. For example, in the book at Alberts biology, does this, how calls? This little drawing is the one that says yes that if DNA, if the space between each nucleotide measured 1 mm, yes? Throughout the DNA a cell could cover the width from the African continent, right? Imagine the length it has. There are estimates that They say that if I take out all the cells from a human body, yes, we could travel around the moon 150,000 times or four times travels and back to the sun. And well, there is estimates that vary in number, but imagine the amount of DNA that we have because you will have heard that the DNA of a single cell measures 2 m. That's it we chatted, didn't we? If I could unwinding the DNA of a small cell measures 2 m. And we have billions of cells, that is, imagine the amount of DNA we have in a body, right? That's why it's so long that It is estimated, No? But if I compare human DNA with that of other species, we see that it is not we are the ones with the largest DNA. Here we have for size comparison of of genomes, plant genome floral, mammalian genome, birds, reptiles, amphibians, fish, crustaceans, insects, mollusks and a lot of species. See that human DNA is not the biggest, right? Hey, the mammal one. in general. And something important with this, As I told you, when we say that the Human DNA, the human genome, measures 3,200 million base pairs or 3.2 GBes, It is by ploid genome, it means counting one chromosome from each pair. By what do we do that? For the comparison be a little more fair between different species. Because, for example, there are little animals that instead of having pairs of chromosomes, they have three chromosomes in each pair, in quotation marks. Do you understand? that have three chromosomes one, three chromosomes two, three chromosomes three. Eh, there are plants that have four chromosomes in each pair, six chromosomes in each pair, seven chromosomes in each pair, right? Seven chromosomes one, seven chromosomes two. So, how are they? exact copies, the chromosomes of the same pair are almost identical in the sequences that they have, it would be fairer to tell the length of one chromosome of each stop between different animals or species or plants, animals, insects, blah, blah, blah. No? Eh, so that's why is that aploid genomes are counted, one chromosome per pair. And see here that the mammalian genome, mammals in general, including us, is not bigger that the DNA that amphibians or humans have fish or even insects. And the Flowering plants have much more DNA big. I'm not telling you that as I tell you that plants have many more copies of each chromosome, I am counting one chromosome from each pair. Still This way the DNA of the flowering plants than that of mammals and that of some insects too. So what I want to show you with This is the size, the length of the DNA does not correlate with the complexity of the species and that's a bit what we chatted in some class, I think, eh, I think that gene expression, that DNA being longer does not mean that the species is more complex. Yes, by example, insects, eh some mollusks, eh, what me, other animals are simpler than humans, they are not so complex in operation, the mechanism, the physiology that the human. And yet he has the longest DNA, right? EITHER Plants do, eh, have a lot of DNA longer but not more complex that the human, do you understand? So, Just because you have a lot of DNA doesn't mean that have many genes. You can have a lot DNA that has no gene function, no It has no function. Yes, let it be one Long DNA that remained like this in evolution, but but you don't have more quantity of genes, yes? Eh, or you don't produce many proteins. As human storytellers with a similar or smaller amount of genes compared to other animals, we can produce much more quantity of proteins, for example, by splicing alternative, which makes it more complex gene expression, No? I compare, for example, here I have Humans have more or less 20,000 25,000 genes for proteins. This microscopic worm that has 1000 cells, it's very small, eh it has 19,500 genes to make proteins. No there is a big difference. And clearly a worm of millimeters in size is more simpler than a human, right? But the number of genes is not very different. So what's going on here? as you can see, eh In science sometimes I can find these differences and say, "Ah, what does, I don't know, what it does to the human be more complex that has more genes, but there are, I don't know, 500 genes of difference, there isn't, there isn't much more difference." So you have to be careful with that. Yes, there is no need to do that. direct causal relationships. In this If that happens, humans let's have a small difference of genes with other animals. So I say, Well, the number of genes does not make the difference in how complex or Simple is a species, but what it does the difference is in how they express themselves those genes or how many proteins we can manufacture with each of our genes. Yes, see the rice and the corn, the number of genes they have, which is much larger than humans. And yet We are more complex species, aren't we? Good, and to try to dispel myths a little that you can sometimes hear that the Human is an evolution of the monkey, in reality is misunderstood by those who Darwin was studying when that is said, because the human is a monkey. It is a kind of monkey. Yes. An African monkey. Because the common ancestor of the primates, of the hominids. Yes, he lived millions of years ago and over time They were opening twigs, they were evolving. Yes. And eh today we have that all primates, including us, yes, we come from a common ancestor, but it is not that the monkey was evolving until it transformed into human. Yes, that's a fallacy, let's say. Yes, the closest one we have, the monkey closest we have to us genetically very very similar is the chimpanzee, right? Hey, that had a center common long ago. And here in this little tree where the human being is, there would be many more twigs of human species than not they are here because they became extinct. Now heard of the Landerthals and a lots of species of homos of humans, let's say, they became extinct, No? Half a story fast to tell rapid evolution. Millions of years ago years, 2 million years, yes, eh we had a lot of species of homids that emerged in Africa, the first humans, let's say, yes, they emerged in Africa and from there they migrated to Europe and to Asia, well. And the species that predominated in the Neanderthals in Europe. These Neanderthals interbred with Homo sapiens that emerged in Africa, which it's us. Yes, they crossed and so we were having a genetic mix until reaching having us. Okay, I'll fast-forward a little bit. What this shows is that if homo sapiens of Africa would have caught fire bonfires, fire, the Neanderthals of Europe would have seen them from one coast to the other. another and they would not have known that they had to They were different species, but they they would have seen it for sure from afar. But Well, they have been able to cross from one continent to another in that moment. They have crossed, they have had relationships and hybrids have emerged, as well how hybrids between horses and donkeys so that mules may emerge. By For example, humans have a mixture of DNA in our genome, of DNA Neanderthal, yes? Apart from sapiens DNA, of human DNA, right? Good. And recently it was discovered that there is another species of domains that existed at that time that were They call Bans, who were in how do they calls? In Siberia and that we also have DNA of that kind of domains. Not them I'm going to bore you, but basically these hybrids of Neanderthal and other species of domains were able to migrate throughout Asia to America. And here we arrive we basically. Yes, we have DNA African and Asian DNA, basically. And this basically shows the same as half of our DNA, eh, although he is Caucasian, right? and European. We have the other half of DNA who is Amerindian. Eh, something that when It is said that we come from ships and that We have no original DNA. lie because half of our DNA is from what's his name? Of Amerindians who They have crossed paths with the Spanish in their moment. Well, nothing, blah blah blah. This It's a bit of history, the same. Come on to advance the issue that what we studied the other time in biology, We saw what a gene is, what it is sequence, which is the basic unit of inheritance, which has information for encode to a trait, right? A one phenotype, a character, if as it may be eye color, among other things. Hey, and these AN sequences can be inherit from one generation to another, by that's like the little block, the unit minimum of inheritance, genes. AND has information that they encode for non-coding arenas that meet a function in the cell or for arenas messengers that are translated into proteins, Yeah? and they are also the products functional, the workers of the cells, right? We saw that genes have sequences eh exons, right? And introns, sequences that have information for make the protein and sequences that do not provide information for the protein interspersed. Do you remember? These are these genes nearby we have a DNA sequence which is the promoter sequence, which is essential for reading to begin of any gene in any cell. the promoter sequence was glued proteins, right? That gave rise to the transcription factors basal transcription, RN polymerase and this gene begins to be transcribed to an immature RN, a transcript primary. As it matures, as long as the RN is being created, it is maturing, No? Eh, and then further, right?, from the gene we have regulatory sequences like enhancers or silencers where stick specific factors of transcription that vary in each type of cell and make different genes whether they are on or off, it depends on the cell, right? This ripe renin, yes remove the belts, stick all the exons, the important sequences, the protein recipe, has its extreme sequences that are not translated, UTR sequences are called, where could where we could protect the messenger to be destroyed or sent to destroy, for example, by micro RNES. This then regulates how stable Messenger RNA, these sequences in sky blue. I have the hood and the tail police. Mature RNA exits into the cytosol. Yes. And it is translated into proteins. Well, we saw that genes have eh humans roughly between 9 and 10 hexons and that there is always one hexon less than introns, right? Because? For the translation I have the start codon, three little letters A U G in the RNA that They say, "Hey, here starts the message for make the protein." From here on you have to read ribosome, right? The first exon. In the last hexon I have the codon of stop. You saw that in the exons I have every three little letters is interpreted that there is that brings an amino acid into the translation to make the protein. So, the stop codon, the one that says, "Hey, here finished the recipe," is also in the last exon. So, as I have to read the start in an exon and read the pause in another exon, I don't have to start and finish reading an exon and introns They are interspersed, there will always be a intron less. Here I have 1, two, three hexons and two introns. It's always like this because the message to make the protein It's in exons, that's basically why. Yes. And be careful that the start codon of translation is not important, it is not known interprets so that this DNA is copied to RNA in transcription. The ARN polymers do not care about codons, is it understood? Find the promoter, Start reading from here, from the sequence that is not translated and all this transcribes it to an RN without caring, without interpreting codons. The fact that interprets the codons of RNA to putting amino acids is the ribosome in the translation. I say this because sometimes when we talk about the start codon They think it is so that the DNA can be transcribe to RN and it is wrong. Yes. Here I have the gene, connections and introns, coding and non-coding sequences interleaved coding. The polymerase transcribes RNA. By splicing the sequences that do not provide information cut and degrade. The exons are they join. Yes. And this RNA all stuck together. with all continuous sequences can read to produce a protein, No? So far we are fine, but with this review. Yes all ok. Yes. If you go very fast or something, they want to not remember something, I they say. Yes ok. So, uh, DNA we know he's not naked. First of all DNA is a double helix that has phosphate group, sugar and base nitrogenous, which can be AT, C or G. Yes, C goes with G, A goes with T always. And this double helix is ​​not naked. This DNA is attached to proteins, to a complex in reality of eight proteins, right? A heterooctamer of histones. And this is the basic unit of chromatin. Chromatin is this association of DNA plus proteins, the smallest part which is these ochoas with two turns of DNA, we call nucleosome, which are like pearls of a necklace, right? These nucleosomes are going away bundling, rolling, coiling, rolling, rolling, rolling. In the M phase, in metaphase, in division cellular, the highest degree of is formed compaction of chromatin, DNA, what can be rolled up the most, which are the chromosomes, which are very coiled to protect DNA from breaking in all the shaming that he suffers in the cell division, right? Well, here we have the same Basically and this is what I wanted to ask arrive that e the before not not so long ago the DNA sequences were not known human. Yes, in the 70s, 80s and 90s We started saying, "Hey, let's meet human DNA from end to end because it is not We know him, don't we?" And that project involved a lot of groups scientists from around the world. was called a human genome project and a lot of research consortia in all the continents, all over the world, that They started taking samples from people, Yeah? And sequence them. sequencing them is know little letter little letter how it is eh the DNA sequence and began to sequence little letter little letter the sequence a lot of people to see if to see the similarities, right?, of the Human DNA, how similar or not? we are all and know end to end the Human DNA. Well, when the first draft said, "Hey, we have more or less finished the work." And when It was finally finished and published in scientific journals, in Nature, in Science, yes? In 2001 and 2003, 2004. And in due to the technology of the time, it is not possible could continue moving forward. In the DNA that is very compact at the telomeres, in the tips of a chromosome was complicated to sequence, knowing the lyrics well little letter without fail. When the best techniques to be able to know sequences of DNA, the entire sequence was completed DNA from end to end at last, which was missing in 2022 and was published this year magazine stage in the magazine scientific Science. So, the main objective of the genome project human was to know the sequence complete, end to end of our genome. And that started in 1990, right? AND as it says there it involved a lot of people, a technique was used that was called the Sanger method or sequencing of sanger, which we will see in the next class, which is to get to know letter by letter, a sequence unknown DNA and that is used today in day, although it is used less and less for e diagnose diagnose eh mutations and yes, when a comes patient that I clearly do not know his DNA sequence, eh if the patient doesn't has changes, mutations frequent symptoms of a disease, capable of has a rare or semi-new mutation, we sequence, that is, we know the little letters little letter, what's wrong with it? And also sequencing is used to know new viruses or bacteria. For example, when the COVID pandemic occurred, it is that it was a new virus that did not we knew, we had to sequence the COVID virus genome, know letter a letter how that genome was. So, the idea of ​​being able to know letter by letter a DNA sequence, an entire genome of any species, virus, bacteria, animal, eh whatever, plant, it is know what sequences it has, what genes It has, the functions, a lot of things, basically, right? The first draft that was more or less 90% The sequence was published in 2001, right? AND the first human reference genome that they were, that is, it was like a compiled from many genomes, from many people, we said, "Well, here we have a typical reference genome that shared by many people. And it was published in 2003, right? And he had 90% of the genome. What was missing was to finish sequencing sequenced in 2022. Yes, here are the important project directors. Crikeinter and I'm burned out now, sorry. Uh, Cry Venter, uh, Collins and, how do you calls? Eric Gream, who was the director of the of the part of genomics of the United States Institute of Health, of the Ministry of Health of the United States Joined. Eh, Coso also participated James Watson, who is the one who discovered the double DNA helix. You've probably heard of that one. Watson and Creek model and that a little They also stole information about Rosaline Franklin to know the structure of the DNA. Well, this guy is very iconic in what he did in discovered the DNA also participated in the project human genome and here the conference of press with the President of the United States United, Clinton, when it was finished by end of sequencing the genome in 2003 human. And recently, not so much, in 2023 chromosome I has been sequenced, which was not really known well either well from end to end the sequences of the chromosome I, because it was also difficult to know. And in 2023 it will finished sequencing, luckily the human chromosome I, from many samples from a lot of people, obviously, right? Because there are variations between people in DNA and those variations are gone studying later, how equal or how different our DNAs are and Now I'm going to tell you. So, what which was known from sequencing all human DNA and a great deal came disappointment because the researchers They thought, "Humans should have more or less 100,000 genes, that is, we are one complex species, I don't know what and the The reality is that they were surprised by that we have more or less 30,000 40,000 genes, of which 21,000 25,000 genes They are for eh proteins, for r messengers and proteins. That is, it is much less the number of genes we have for proteins than previously thought sequence the human genome. What how is the composition of the human genome? I want you to pay attention here. The half of my DNA, 50% of my genome is single copy sequences, that is, they do not are repeated. And here it includes the genes and extragenic sequences that may be, for example, what are they called? the regulatory sequences of genes such as promoter sequences, enhancer sequences, silencers, non-translated sequences, UTR and and so on, right? Uh, those sequences and of other sequences that do nothing, basically eh they are here. The genes involve more or less 20% of all my genome, but as I told you when you gene expression that the cintrons, the non-coefficient sequences are much more long, it doesn't have much more size, but exons. If I wanted to think how much eh of my DNA are exons, how much of my DNA has information to manufacture proteins, how much do you think it can being, how much in my DNA is to do proteins in percentage seems to you. Throw what percentage of the genome is exons. They are 6%. How much? 10% or is it little, eh? No, that's much, much less. 2%. Good. 2% almost. Yes. Imagine difference from what one thinks that everything My DNA is genes and all my DNA is for make proteins or many think or we thought, I included that before study this. What is inside a gene, Genes are 20% of all my DNA, but within a genos, the larger the belts are than the exons. So I say, "No, the single sex, the sequence that has the recipe to make the protein, "How much is it?" Less than 5%, 2% of All my DNA sequences are for make proteins. Nothing. And for a long time called everything else junk DNA, evil called because we know they have have functions, even if they are not sequences of DNA to make proteins, they have a function some. Well, we've already talked about half of it. of my DNA. Let's go to the other half. The other half, the other 50% of the genome human are repetitive sequences, sequences that are repeated, separated, spaced or side by side the other that ends, starts again, ends, starts again. Yes, those are repeated sequences. We have sequences large repeats that are in the middle of a chromosome, at the centromere and at the tips, at the telomeres. Are sequences that are repeated a lot, that begin, end, begin, end, they start, they finish, they have one structural function. First I want you to think about this. The sequences that are repeats are not genes, okay? Just because They repeat themselves a lot, they are not going to make one protein that has all amino acids equal. So, they are not sequences encoders, has no information for make protein. Yes, in general. So, the repeated sequences They have another function that is not to do proteins, but a structural function to give shape, support, structure to a chromosome. The entire region of the middle of a very strong chromosome are sequences repeated and the ends, the telomeres also. And I told them that with each DNA duplication, the ends of a chromosome, telomeres shorten and do not It doesn't matter because they are sequences repetitive, sequences that repeat themselves a lot and since they are not genes, if they break the cell does not know basically unless you cut a lot and we are already at risk of damaging genes. We also have fossils, let's say, of DNA. eh, retrovirus, that is, viruses that They infected us throughout the evolution, as I showed you, of all the human species, yes? and ours ancestors ancestors. Hey, we have a lots of virus DNA in our DNA human. You saw that the viruses, I told you, RNA viruses, such as the HIV virus, has the ability to copy itself to DNA, make a reverse transcription, a reverse transcription, and that viral DNA can get in between my DNA, the host cell and can remain there latent for a long time and can be reactivated and re-infect with HIV, for example. But today we have virus DNAs that were infecting us throughout the evolution and are inactive, no longer They work more, they have shorter DNA, broken, which undergo mutations, but I have, If I look for my human DNA, we have DNA viral. Yeah. Uh, and we have sequences that They were active before and are no longer active. active ones that are called transposons DNA or elements are also called mobile genetics or informally jump sequences. They are sequences of DNA that can leave the place where they are are. For example, imagine I have a DNA sequence on the chromosome one. It cuts and moves and that one goes away. DNA sequence to be inserted into the chromosome, what do I know, five. Sequences that can jump from where they are and go to elsewhere or copy and go elsewhere. So, in this one I have sequences that They are repeated, separated in my DNA human too. Yes, we are going to talk about that. That, sorry, that would not generate a mutation. as when leaving your space. Good. Yes, very good question. Yes, the true that yes, when leaving your space could generate a mutation there and then if inserted, for example, between of a gene, I could alter a gene, right? It would be a problem if I had a gene normal and suddenly one gets into him sequence in between, a sequence random in the middle. Uh, well, by Luckily that doesn't happen anymore because you are sequences are also considered as fossils, eh, that are no longer jumping over there, they are already asleep. Are sequences of n that have already lost function for mutating. Yes, some of them sequence today is active and very rare documented cases. It happens that that sequence when it jumps it gets between through a gene and causes a disease in the person because it alters a gene normal and the person gets sick. Hey, it is very strange, but it has happened. Yeah, now I'm going to show you. Okay, but yes, yes, yes. Of course, they are like fragments nothing more than they are not active. Clear, Most are not active, some few do. Now I'm going to show you how they make to jump. Yes, exactly. The Repeated sequences are classified into dispersed, than those of us who are chatting, the scattered repetitions I have a sequence here, you see? In another chromosome, in another place of the genome, I have it repeated again. When I go to another chromosome I say, "Hey, I had already read this one before." Well, They are scattered repeated sequences that can be copied and that copy can jump to another side. Or tandem repetitions. In tandem means that they are and placed, contiguous, that is, one sequence that ends and begins, ends and it begins. See? T a jegje, tjeje. Tjejje and so on. These are the sequences found in the telomeres of my chromosomes. These are six nucleotides that repeat and terminate and They end and so they keep repeating themselves, right? This is called tandem. Hey, let's see. the importance of these tandem sequences. First, yes, the repeated sequences in return, the Repeated sequences are not genes, right? They do not contribute, they have no information to make proteins that help us in some way we are not sequences encoders. Yes, the repetitions in tandem. Eh, it has another function. different from what is structural. Well, the These repetitions are in tandem, so in a row and in small blocks that They repeat and repeat and repeat one another side by side, they are classified by sizes in three in satellite sequences, the ones with bigger blocks, Yeah? And that together all of those blocks are very large, so example, that each block is very long and in total all the little blocks of repetition makes a long sequence, No? Those are the satellites, they don't have What are the numbers, I'll just tell you. Yes, they are repetitions of between 5 and almost 200 base pairs and together all the blocks make 200,000 foundation walls. Well, these are very very long repeated sequences satellites are at the center of a chromosome, at the centromere, which is what that joins this little arm, short arm with long arm, it is what allows to join after DNA duplication another leg of the chromosome, the chromatid sister, the identical copy of this chromosome. They join at the centromere and in this centromere are also embedded protein complexes, remember? Which is called kinetochore, which is where will embed the fibers of use, the microtubules, in metaphase and anaphase for tug and blah blah blah. So, the centroo has a structural function structural to give it shape, support and addition to the chromosome. Yes. And participate in all those things, those processes. After we have shorter sequences, the mini satellites, right? Sequences between 9 and 60 base walls. And these sequences repeated a little more short ones are in the telomeres, in the ends of my chromosome. Yeah? Are sequences repeated in small blocks They get shorter with each doubling of the DNA. Well, because of how duplication is DNA, every time a duplication occurs the end of a chromosome is shortened. As they are repeated sequences, there is no damage to the cell is not even noticed because it is not It is a DNA that provides information to pass proteins or anything, but if you cut a telomere too much, we run risk of starting to cut genes in following duplications and there yes the cell would fail and die, obviously. So, the card can census, detect the length of your telomeres and say, "Hey, I've already been through a lot cell cycles, I shortened my cycles a lot telomeres, I'm old, I'm aged. I'm going to break the cycle cell phone before damaging my genes. That is called replicative senescence or that cell is senescent, remember? The cell cycle that is in G0 comes out because it's old, basically, and it's a cell that does not work well, that has the altered metabolism, has damage to the DNA, uh and uh induces inflammation in the surrounding tissue, it's like cells aged which also makes you age the tissue and that's why we age us. When the telomere shortens much and the cells stop renewing, to divide, to give rise to daughter cells, These aged cells die, they are not replaced by new daughter cells and we grow old and die. So the telomere length a little bit It tells you about biological age, right? AND the age of the cells, eh, or that they are aged or not. And then We have the microsatellites, which are smaller sequences, repetitions even smaller. that are in many sides of the genome, basically no is that they are in a specific place of the chromosome. And we are going to see the importance that have these repeated sequences micro and minisatellites that do not have one specific function in the cell you have found, but as I tell you it is It has a function that humans have given it given. And now we're going to see why. Because these sequences that are repeated of small blocks vary greatly between people. Yes it is said that they are not subjected to evolutionary pressure. That means? Genes, for example, do not vary that much. between people. The gene, the sequence little letters of the P53 gene, for example, or any protein, you know what I mean? The gene of any protein, the sequence does not It varies a lot from person to person, because if That gene mutates or changes the sequence, eh a person would get sick and die and not would give offspring, would not transmit that variant to the offspring, right? So the genes, which are important sequences to do proteins, do not vary much between people, are under pressure evolutionary. If they vary, they get sick and die people, right? And that conveys that DNA. These sequences that do not have a information to make proteins or a damn, eh, how come they don't have that function, they can mutate, right? And in general due to duplication errors in DNA, eh, when there are repeated sequences tend to expand more, to repeat themselves more and more and more and more and more and more and more. So, as they are not subject to no pressure, these sequences mutate, they lengthen, they lengthen, they lengthen, they they lengthen, the repetitions lengthen, the little blocks of repetitions and they are highly variable in each person. Me explain? For example, this sequence punctual A G A. A person has seven blocks of repetitions, another person has four, another person has 12. That is, you see that the same sequence of DNA varies from person to person, right? So these repeated sequences, the micro and minisatellites, which are called repetitions of variable length, That's why they vary from person to person, right? HE They call sequences that are polymorphic, Yeah? Highly polymorphic sequences. Polymorphic, polymorphism. Do you know that? is it a polymorphism? It means that it is a polymorphic sequence, which exists many forms, there are many variants of the same sequence. What varies in These sequences between people is the number of repetitions, the number of little blocks, right? And they are considered polymorphisms when the sequence is present in more than 1% of the population. What does it mean? For example, this one person has a repeated sequence seven times, seven little blocks and this one sequence shares it with 1% of people, with another group of people. Another different group of people will have another number of repetitions. Other number of people in another group of people will have another number of repetitions, do you understand? That is, it is not that vary in each human, it is totally distinct. I mean, there are people who They share that they have the same length of some sequences. Yes. Uh, then There are some sequences that are shared between people, but if I take all the distinct repeated sequences that there is in a person, here I am seeing one A G A T, there will be a lot of sequences different ones that are repeated from to little blocks. If I take all the repetitive sequences of a person, I'm going to see that the combination of sequences that person has, of numbers is unique to each person. So, I can identify people different due to the repetitions that have. Yeah? And I know that for each of these sequences, yes? Eh, for these sequences I have two copies because as for example this sequence can be on dad's chromosome one, right? AND I have a variant of that sequence in the chromosome one from mom. It is understood if I In each chromosome I have the sequences repeated twice, we said before, didn't we? Each sequence has two versions, two variants. The variant that your dad and the variant that your mother's. So, a boy here's a sequence, right?, of the mom and the other dad. Yeah. So, I can use these sequences repetitive, micro and minisatellites such as genetic fingerprint is called for identify people, whether in genetics forensic to identify criminals or in parentage tests, yes? For find relationships between people, by example, fathers and sons, and, mothers and children, eh, her do eh, what's her name? this? Test between siblings or for grandchildren and grandparents. So, for example, here I have an example of a child, his mother, son or daughter, his or her mother and two possible parents, two possible culprits to parents, Let's see who the real father is. What is done is by PCR, do you remember? of the PCR? Eh, find many distinct repeated repeated sequences of a person, yes? Increase the number of copies, clone it, amplify them by PCR and compare the weight of the sequences, yes? of a son with the sequence of his mother and the potential parents, right? Here I am separating the sequences by weight DNA. So, I know that this sequence It's light, this one is a little more heavy, this one is a little heavier, a a little more, a little more, a little more and So. So, for example, the boy for a repetitive point sequence any, I don't know, AAT, a sequence random that repeats itself, right? That ends and starts again. AGAT, AGAT, AGAT, AGAT, yes, it is repeated in tandem. This boy has a variant, that sequence repeated a number of times that inherited the mother and the other variant the father inherited it, yes or yes. I would like to see of what of whom of the two men inherited the sequence. See that, for example, this band coincides with that of the mom, right? And this band up here matches father one. Yeah? This band matches this father's too, right? Let's see, this band matches with the father one too. This also, this one too. And so we go seeing. If I go connecting and I know that Father one is yes or yes the father of this one boy or girl, yes? Because my sequences repetitive DNA or any sequence GN, whatever, half of my sequences come from mom, the other half from mom and dad, I mean, sorry. No, For each sequence I have two versions, two alleles that are on the chromosomes of a pair, in homologous chromosomes. So if the boy has this variant, mom, the other variant is the dad, yes or yes. Yes. And like the little number of repetitions of blocks, it varies a lot between people, yes? I know that all These sequences repeated, yes, half, let's say, They are from this father and cannot be from the father two because they do not match in the weight, do not match the number of repetitions. Yes, the sequences of this guy with his son's and half of the sequences of this son have to to be the father's. So, I know that the Father one is yes or yes the father and not another person. Do you understand? When I evaluate, if I evaluate a repetitive sequence, may coincide among some people, but if I compare many sequences different repeated, I know that the block repetitions, the length of every sequence of yours, of all the sequences of yours, it is unique to you. By That's what I say, it's like a footprint genetics. It is understood, I am the long one, but it is more or less understood how it is used this or more or less. Yes, yes, yes. We're doing more or less. good. Hey, any questions let me know. forensic genetics. Same here. Have in a shows samples of scenes from a crime. Yes, here I have a sample of three vari of three repeated sequences. Yeah, three each repetitive sequence eh I have two two variants, right? The variant that one of a father and one of his mother. Here I have three sequences, yes? Each sequence has both of its alleles. I have to see which of these three suspects is this sample of the crime. This blood that was found, by example, of a criminal in a sample from the crime or DNA from saliva samples or of semen or hair or whatever. AND I have three suspects here. We extract DNA of the three. I see the weight that the sequences, yes? Those sequences repetitive, micro and mini satellites, No? What are tandem repeats and which vary greatly between people. So let's see that the weight of these sequences match that of the suspect two, right? It's okay that, for example, this band here also the one from the guy one matches, but this one another does not match. So there I say, mm, weird. Maybe this guy isn't. This sequence matches all three. We [ __ ]. This sequence with these two guys. Do you see that there are sequences? that I say the number of repetitions, I have a sequence with with eh repeated three sometimes, for example, eh a little block repeated three times, four times, it can match between two people, but the set of all sequences is unique for each person. Yes, here I see These blue sequences match this guy, then the one who matches, the one who exactly matches this DNA is the guy two. That is, this sample I confirm that it belongs to this guy. He suspect two is the culprit, he is the criminal. You see that comparing, if I I compare a single sequence, it can be shared among many people, but comparing many repeated sequences different, the combination of the variants that the guy has that his dad and his mom, if the combination of repetitions is unique to him and not to another person. This person has some that shares, but others that are different. In the block of repetitions This person has other different ones, then it is unique. Yes, it is a footprint genetics this. Well, here we can see it same as a means of task that I with the previous topic. Then the cell dies before reply eh yes, when with the subject anterior, the telomeres are gone shortening with each DNA duplication. That's what usually happens. When they arrive at a critical length, that is, when they are very the telomeres are short, the cell decides stop dividing before damaging genes. Exact. The cell cycle comes out as before. Yes. Or you may have suffered some equal damage to DNA. But yes it is known that the telomeres are very short and come out of the cell cycle. Here we have another example, Jewel, another example of three couples, yes? Male, female, that is, father, mother, father, mother, father, mother and three you drink. One has to compare whose baby is which. By example, this sequence, baby one, with which partner does it match? Set a rule. With the A. Uh, no, with the B, with the B here. Perfect. Good. With the father the B. This sequence, this sequence here, with who does it match? It doesn't match here, do you see that it is? a little further down with B too? Good. This B. Mother of B. Good, perfect. Well, I'm comparing like this. Tiki tiki tiki tiki, baby one is the couple's baby B, right? You have to see whose baby two is and baby three whose is it. So, You see that I am comparing many sequences that change the number of repetitions, I know that the combination that is unique You have this baby, right? Uh, with others babies, that is, between each person is only the repetitions that there are. Well, and I can know if the father's heir or from the mom and blah blah blah. Same here, Hey? So what is done It is eh sequencing, sorry, anyone with PCR, increase the number of copies, Yeah? Eh to be able to see the results and measure the weight of many sequences of distinct DNA, repetitive sequences that can be on any chromosome and is used in autosomal chromosomes, sex chromosomes, blah blah and also mitochondrial DNA is used. So, I Here I analyze many sequences different repetitive ones, right? And we see that in it is put, for example, here it says son and alleged father. Hey, I have some numbers here. How long is this guy's sequence? For example, this kid. This baby has a repetitive sequence, has a variant, a Lelo with 16 repetitions and the other variant that another father with 18 repetitions. Yeah? This means the little numbers. So, until you see the class? Eh, I think half is missing. an hour or so. Yeah. So this guy has uh a sequence repeated 16 times and the other variant of the repeated sequence 18 times. A variant has to come from mom, the other variant of dad. So half of your sequences they have to come from their father. Yeah? Yeah they agree, this is the father. But they agree, he is not the father. How much does it have? to match? And in 90-95%. If I grab 14 sequences repeated, there may be a difference in two, but two, three, but it has to almost all of them coincide. For example, Here, is there any sequence that the father what happened to the baby of these two? The 16th. Well, the father passed on an allele to him with 16 repetitions. The 18th inherited it from the mother. Good. Here the boy has one a repeated sequence. A variant seven with seven repetitions and another variant with nine repetitions. He Did dad pass you any? No. Good. Not here either. Not here either. Here neither. So, I'm seeing what there is a lot that don't match. What do you want? say? If many do not match. That he is not the father. Well, this is not the father. That's the bottom line. HE understand? What happens when I see a single little number? It means that your two versions, its two alleles, maternal and paternal, they have the same number of repetitions. That's what this means. Yes. But well, eh, he's not the father, okay? If not, half would match the dude, then he's not the father. Yeah, this shows the same thing. The PC, yes, sorry, sorry. Can it only be done with PCR this or is there some other technique? HE It is usually done with PCR because it is the most cheap and easiest, eh, but yes, the The standard that is always used is PCR. Yes, yes, yes. I increase the amount of copies of a sequence and by elphoresis I separate the weight and measure the weight and so I know the number of repetitions it has more or less. Clear. No, nothing. Yes, obviously. To make the para do the PCR, you saw that you had to have a specific sequence that you would like to amplify. This is the same here at DNA. Clear. Exact. All of these sequences are known, they are known, let's say. That is, they are polymorphisms. Yes, they are not polymorphic. It means which, let's see, means that they vary a lot between people in the block repetitions, that is, how many times repeat. For example, here I have one sequence that is AAT and the and how many times it is repeated varies in each person. But if I know, I know that a sequence on such a chromosome it has these four letters, I can make a primer that that is complementary to this. After the block of repetitions no matter what vary between people. Yes, but I I know which little letters are being repeated in each unit. I can make a first that sticks, right? Uh, sure. I mean, you You should already know the sequence that you want to amplify. Clear. Exact. And why do we know the sequences? Because today we know the entire human genome, we have already sequenced all human DNA, right? So it's because That, otherwise we wouldn't be able to, obviously. So, as we know everything today human DNA and we have a DNA of reference that we share most people, and we can do it this. So, I can make a one first, a primer that sticks to a repetitive sequence, a a or a the limits of a sequence and when increase and when it is copied by PCR it will go to me to generate a longer or more fragment short, it depends on how many blocks of there are repetitions. Yes. And so I can measure weight in electrophoresis. Hey, the el The thing about PCR is that PCR allows analyze a single sequence at the same time each reaction. So how do I analyze? I have many sequences at once? I'm not going to do many PCRs because it would be difficult for you very expensive. There is a variant of PCR that is called Multiplex PCR, which allows the use of many primers at the same time against many different sequences at the same time time, as here we channel many distinct repeated sequences in the same reaction. Yes. Here we have another one. DNA sample, a victim. This is a real photo. DNA that is in the sample of the crime that belongs to the suspect, right? Or from the criminal. And here we have three suspects possible. If I compare the weight of the sequences, see that the position of the bands are different for each person because the combination is unique and the number of repetitions each has person. I know that this sample corresponds to which of the three? To the first one. The first one doesn't match exactly why this sample is the First, it's his. So, you see that comparing many repeated sequences different, I know that the combination is unique to that person, unless you may have a twin, but she is unique. Here it is Same, I have a paternity test, boy, mother, two possible fathers. There is that go comparing. And here we have it same with suspects of a crime. Hey, we have the same thing here too. comparing the alleles of how many repetitions have in a daughter, in her mother and the possible father. There are many distinct, repetitive sequences. Hey, So here I have, for example, this daughter has a variant with 16 repetitions that he inherited from his mother and variant 19 repetitions inherited from the father, right? Here's a helo with 13 repetitions created from the mother and one with 16 repetitions created from the father, right? AND So I compare and well, seeing that Yes, he is the real father, right? Eh, and so you go comparing because half of the Your repeated sequences are from Dad, the other half of mom. Yeah. Here we have another interesting case where eh in this work we see different repetitive sequences, yes?, that are in a bunch of chromosomes and repetitive sequences of chromosome I to see if there is an I chromosome in a sample. We have a DNA sample below. what's under a person's nails? woman rape victim and DNA that is in his underwear. Yes, that is found in his in his in his clothes inside. So, comparing, yes, the DNA sequence that exists eh under his nail and on his clothes inside, I see that they are identical sequences, that is, it is the same person, right? the DNA that was found in her nails and on her clothes inside. We would have to see who it belongs to, No? Whose DNA is that? AND comparing and if there is DNA, the chromosome there, yes? Of a man, that is, this that It's here, sorry, I didn't explain it well. The DNA under the one in the underwear is the girl's DNA, the victim. Now let's see if there is DNA from some man. So, I'm going to look for repeated sequences the chromosome there. and we found that it was positive, that is, that under the girl's nail, in the DNA that was under the nails, find repeated sequences chromosome I. Yes? So it has DNA, a man in his nails because he tried fend. Why is there only one little number in each sequence? Because We have only one chromosome there, right? The men have only one chromosome there, or that is, there is a single sequence, eh one unique variant for each sequence. But If I analyze if there is chromosome I DNA In the girl's underwear, we see that there are two little numbers. If I have only one chromosome there, I have a single variant of each sequence, why will there be two little numbers in each sequence in the underwear of the girl? Because I had information about two different people. Good, perfect. Because? Because maybe she, I don't know, had had, I don't know, for example, relationships with a person and then suffers the assessment. Well, maybe. Yes, it could be. Good hypothesis. In this case, eh, Spoiler alert, in this case it is a woman raped by two different men. Yeah, but see how doing analysis genetic and I knowing that there is only one chromosome there, there can't be two variants for each sequence of, sorry, there can't be two variants of the genes of the chromosome sequence. If we find two, it means they are two. different men. Yes, but well thought, just like you said. Perfect. So, here I can use repetitive sequences to do for do forensic genetics. See? And if I had the suspects and took their DNA, I could know exactly who it is DNA, because the combination of all The repeated sequences are unique in everyone. Yes, we have understood up to here this. So, maso, The topic of the issue was not clear to me the chrome markers there. Yes, the idea is that I can find sequences that are repeated in blocks, so any sequence that is repeated in many small blocks and that vary each person. These sequences may be located on any chromosome, of the chromosome 1 to 22, on the X chromosome or on chromosome I. Any chromosome There may be repeating sequences of in small blocks, repeated sequences in tandem. What I show you here is that eh I wanted to see if there was chromosome DNA I on the girl's nails to see if there was DNA from some man. in the united of the girl if she tried to defend herself. So, analyzing different repeats of chromosome I, I see that I find a sequence that repeats itself 18 times, another sequence is repeated 14 times and blah blah. Why is there only one little number? Because we have a value unique i. That is, for the rest of sequences, why are there two little numbers? Because a sequence I have a version on dad's chromosome one and on the chromosome one from mom. For another, in the I have a chromosome five from my mom variant of a sequence. The chromosome 5 dad I have the other version. So for each sequence I have two versions because I have chromosomes of pairs, but the chromosome Io or or rather the sequences that there are in the X and Y chromosomes different. That's why each sequence has a single copy in which the chromosome I. If I find two distinct sequences of chromosome I is because it is from two different men. Because the sequences of I and X do not They are the same as the rest of the pairs chromosomal. Yes, that's why. Okay, there. goes. Yes ok. I didn't tell them the name, but these repeated sequences micro eh Micro and mini satellites are known as strs, short tandem repeats, means, or bta bntrs, means tandem repetitions of numbers variable. Yes, they are the abbreviations that You can read them there, but they are that, micro and minisatellites. They are used as genetic fingerprint, you see? In genetics forensic or kinship testing. HE uses some PCR that allows analysis many different sequences, yes? different repetitions at the same time. Well, they are separated by weight in the electrophoresis and we measure the weight of each one and we compare between different ones people. That's multiplex PCR. By what variants are generated that eh sequences that vary greatly in number of repetitions? By two mechanisms. One due to an error in the crowing over, in the exchange between chromosomes of the same pair that occurs in meiosis, the gamete production. At first a recombination mechanism occurs homologous, right? Dad's chromosome one and one from mom, which are almost the same in the sequences they have, they come together, bits are exchanged to generate a recombinant DNA, a mixture of DNA from dad and mom so that in the species there is variability, that is, so that each child is different and we are not all clones. In the production of gametes produces a mix between the chromosomes maternal and paternal of the same pair there is variety of DNA or for the DNA of the son is different from that of the father and the mother. Yeah? Hey, that crossing over, that is the exchange between chromosomes of the same pair, sometimes it goes wrong. By what's wrong? Because chromosomes They are misaligned, out of phase, do you see that? are not at the same height? Being half misaligned a closing occurs unequal over, it is called an exchange which is not even, which is a shorter chromosome and one more chromosome long. The longest one has the same repeated sequence on the side. Do you see that? I have a sequence and it repeats next to it. If this happens many times, I'm going to have tandem repetitions in a row. It ends, it starts again, it ends, starts again, which is what we saw before, right? And it can also be because errors during DNA copying. When DNA is copied like this in little blocks, tends to expand the number of repetitions due to errors that the DNA polymerase when it duplicates, when copies DNA. It may tend to happen that eh DNA polymerase along with the daughter chain that is being manufactured, no reading a mold, the mold may come off mold, can be separated and when separated the daughter strand and the polymerase, if it reattaches to the mold, it could be glued further back in a place you already copied and copy it back and extend the number of copies without want for duplication errors. Yes, if these sequences were all different, they were not repetitions and the mold and the daughter strand detaches and wants to stick to a place again incorrect, no no there would not be a union, a pairing, a complementarity of bases if they were all sequences different, but as they all are equal sequences that are repeated from to little blocks, I, for example, this last, these three letters, I can separate from here and stick them here back, yes are equal or not. That is, they are equal complements. That's why DNA It folds, right? And it sticks in one place incorrect. So, it can be done, it can be done copy from more wrongly and increase the number of copies. Yeah? So the cause, if you ask them the cause of the production of repeated sequences in ten, it may be errors during the DNA duplication, right? Or errors in the closing over. That's what I want it to be take. Up to here. Did you understand? Come on good. Passed. Yes. Yes, everything is fine. Yes, all clear. Spectacular. Okay, let's go with eh scattered repetitions, repeated sequences that are repeated, but are far from each other. Why are they generated? They are generated by sequences that I told you about. which are called jumpers and informally or transposable or mobile sequences, that were discovered by a crack scientist of genetics, Barbara Mclinton, and won the Nobel Prize in 83. For this reason discovered in corn. And we have sequences that can jump out of place in which they are and get into the other side or copy and go somewhere else, which are DNA transposons. AND then we have sequences that eh we have sequences that are transcribed to RNA. Yes, that RNA is changed to DNA again by reverse transcription or retrotranscription and is inserted into a new place the genome. This is how the number of copies. They are called retrotransposons. And we have retrovirus-like retrotoses, or It is a genome that was previously virus that infected them and stayed there in our DNA stuck in the middle. Mutated, already It doesn't work anymore, but it's still there. Uh, and we have sequences that work the same, but they do not come from viruses, which are our own. Yes. Uh, and now I'm going to tell you how they do it be copied. DNA transposons. Yeah, are DNA sequences that can be transcribed by RNA polymers. Yeah, when when if there is a there is a promoter nearby, RN polymerase can recognize this sequence, copy the RNA. That RN is translates into a protein called transposase. This transposase protein recognizes the tips of this sequence, that transposon, folds the DNA, cuts and that sequence is taken elsewhere of the genome and will insert it into another new side of the human genome. That sequence changes location, jumps where is. He says, "Hey, I'm bored." By To put it informally, no, I got bored. It encodes a protein, the protein encodes it folds, cuts it and takes the DNA to another to another place in the genome. And so the sequence is jumping. Yes, it is a DNA transposon more or less and can be copied. Now I'm going to tell you why. And we have roughly 400,000 copies of DNA transposons. Yes, more or less it is 3% of our genome, but they are evolutionary vestiges, that is, they are sequences that used to jump around and Nowadays they don't jump anymore, they are asleep now, they can't jump. Yeah. So if the sequence jumps where It goes the other way, it is an increase number of copies and called transposition conservative. See? Cut a new place and is inserted in the middle. It does not increase the number of copies, changed location. Now it may be that yes, eh, yes, it is copy and that new copy goes to another side. That's called transposition. replicative. Yeah. Uh, basically because There is a recombination, but it doesn't matter Well, the mechanism doesn't want to put them to sleep. with that. But it may be that these sequences skip without being copied or by some errors are copied and that copy go somewhere new. Well, that's a DNA transposon. Sorry, I have one doubt. Yes, obviously. And these sequences They can jump several times or jump once time. Yes, they jump several times the same sequence. Okay. And I didn't understand eh put it you have sequence A, which goes from place A to place B. At place A, what remains? Like space and then they rejoin the ends or Yes, good ask. Yes, it is recognized that there is a cut by repair mechanisms. HE try to repair. Yes. Okay. And with it new place where the new joins sequence, yes? It is cut and made as the place, nothing is cut, or not? Hey, clear. No, it is not cut and inserted into the middle. Clear. It is not that it is replaced another sequence to be said. No. Okay. Okay. Brilliant. Exactly. Exactly. No, nothing. Good. Uh, we have sequences that are called retrotransposons similar to retrovirus, right? Hey, they are sequences. very similar to what a virus works. An RNA virus, a retrovirus. Here I have it, see? The capsule that surrounds the material genetic, the capsid, right? One one protein envelope. Here I have the Viral RNA. There are viruses that naturally They have RNA and not DNA, for example, HIV virus, eh the flu virus of influenza, eh flu A, for example, the COVID virus and a lot of viruses They are retroviruses, they have RNA as material main genetic. That virus eh enters the ID, yes? type of receptors that there is in the cell, it is used, it enters, releases its genetic material. That RNA yes eh it's going to be transformed DNA by a enzyme that is called transcribed, yes? So this mold of RNA, well, it codes for a protein, the protein reads RNA and makes DNA, a Complementary DNA. Makes a reverse transcription, a back transcription. And this new one this one new viral DNA that comes from RNA inserted, integrated into the DNA of the host, of the cell it infected. Yeah, because there is an enzyme called integrase, which can cut DNA host and introduce the viral DNA. So, I have my human DNA in there. mixed DNA of viruses that infected, you understand? That viral DNA takes advantage of the machinery of the ID card. When the DNA polymerase the cell transcribes human genes, also transcribes viral RNA, DNA viral, sorry. These RNAs are translated into proteins by the ribosome and those proteins come together to form a new viral particle, a new virus and this is how many are manufactured many viruses within a cell up to that the cell dies, bursts, explodes and a lot of viruses are coming out to follow infecting. This is how the infection works viral basically, right? Well, what's up? with these sequences? These sequences that can you do reverse transcription and get into a new side, right? Transcribe and everything the same and it is the number of copies is increasing. These sequences have undergone mutations. These are sequences that no longer work. moreover, they are mutated, damaged and not allow eh that they are translated to viral proteins and new ones are manufactured virus. They are like sequences that were viruses and they no longer work. Basically yes DNA that comes from RNA and DNA that comes from virus that is no longer there working. Yeah. And it's more or less almost 89% of our DNA. Good. And they are called human endogenous retroviruses or herbs in English. Did you understand how it works? step by step of what do? More or less. Yes ok. And this is it what interests me most because those are not are so important. These repetitions different dispersed ones that are retrotransposons. Retro is because involve a transcription vessel reverse of RNA to DNA, right? Retrotasposons because they can jump, no retrovirals, that is, they do not come from viruses, which are our own. Yeah We have some sequences that can jump over there that are long that are They call lines and short sequences that They are called signs. Yeah? How do they work? these long sequences lines? Yes, it has the information to be a protein that has a dual function or two proteins glued, rather. This sequence is a DNA sequence, right? If there is a promoter close, comes RN polymerase, Yeah? Transcribe the genes you have to transcribe and also transcribe to this sequence line, that is, this DNA makes messenger RNA. This RN messenger by the ribosome is translated into a protein with dual function. Yeah. a protein that has the function of transcript. Yes. Or reverse transcriptase, I mean, what's this doing on top? Grab it. Imagine that, let's see, DNA is transcribes and RNA is translated, right? EITHER Imagine that the protein grabs the RNA messenger from which the protein comes or which was the mold to make it. Yeah? So the protein grabs onto the RNA messenger, reads it and copies it, makes a DNA complementary. Yes, it does. reverse transcription. reads an RNA and makes DNA. Yes, this brand new DNA now takes it to another place in the genome random. Cut because the enzyme also It has endonuclease activity, so can cut DNA and insert new ones this new DNA to a new place in the genome. So, that's how I have the original sequence, it was transcribed, it was translated, above all, made a retrotranscription and that new copy of DNA went somewhere else. Yes. And so it increases. the number of scattered copies. in my genome. Well, if this sequence that is inserted in a new place there is no one promoter sequence nearby or anything, I don't know will be able to transcribe, will not be able to activate again and it will look like a dull, sleepy sequence, right? EITHER incomplete, eh, or if they mutate, stops working. Most sequences These ones that jump around and that are transcribe and others are not working by jumping around, though Some of these lines are there working, sometimes jumping. in my DNA human and these shorter sequences has no information to do these proteins that help copy them, but the enzymes they produce are used the lines, take advantage of this enzyme eh that does retranscription and that for be able to make copies of this sequence and take it to another part of the genome and insert it in a new place. Yeah? So here I have this sequence, transcribes, translates into proteins. The protein grabs the messenger, copies it DNA by reverse transcription and it inserts the genome into a new location another chromosome. Yeah? These sequences are They have seen that they can participate a little in the maturation of neurons. In certain moments of neuronal development in the embryo, in neurogenesis, these sequences that jump are activated, they jump and in some way they are participating in which neural stem cells mature into neurons. We don't know well why what, but eh they participate a little and they reactivate in some processes of the embryo. Yeah, that's something crazy to me. Uh, so here we see an image a little more pretty. The DNA sequence, the retotransposon is transcribed to RN, translates to protein. The protein by reverse transcription reads the RNA to make a copy of DNA. This new copy and insert it in a distant location distinct from the genome. Hey, I have one. scattered repetition. Do you see her? It was held up to here this more or less deck. Yes. Yes. Good. Yeah. So if you ask them the tandem repeats, what are they or How are they produced? They are the satellites, mycosatellites, myselites, which are produced by duplication errors DNA or crowdingover errors. And if They ask them about repetitions dispersed, are produced by the activity of mobile or genetic elements transposable, right? The repetitions dispersed are by transposons, retrotransposons, good. So don't confuse. That's the difference. Yes. Well, this shows the same thing and same basically nothing. Here is a transfer of DNA, retrosposon, basically the same thing. Well, we also have genes today that no longer work, that used to be genes at some point in our history evolutionary and are no longer genes, which are pseudogenes. Pseudogenes are, as it says here, evolutionary vestiges. They were genes previously suffered mutations and no longer work. For example, It may happen that a gene due to errors in the DNA duplication, a gene is duplicated, That is, a gene is duplicated, copied, that new copy acquires mutations and no longer works more. It suffers mutations, cuts, damage and is a non-functional copy of a gen. That's a pseudo gene. Yeah? EITHER It may also be that because retrotranscription eh a copy is made new, but well, it mutates and doesn't work further. Those are the pseudogenes, basically. Yeah. and blah blah blah blah blah and eh this is it we can skip, but basically when In ancestral genes there are genes that are have duplicated, yes there are very genes similar, but not the same, that produce proteins of the same family, by example, proteins of the hemoglobin, yes? Eh, from the blood, from red blood cells. We have two chains different, alpha and beta globin, are two proteins that come from genes eh of the same family, from an ancestor in common. also the myoglobin of the muscles and these ancestral genes They were duplicated, copied, gained mutations or to generate proteins similar but not equal or suffered mutations to generate pseudogenes that They basically don't work anymore. But all these related genes that are similar, which in evolution are generated by duplications, are gene families. Yes, basically also the genes for ribosomal RNES, which are genes that are copied many times times, I told them, eh, they are families genetic, if they are multicopy genes that are They have copied many times in evolution and also the genes of the receptors olfactory that allow us each protein, there is a lot of protein, Look, a lot of genes for a lot. of different proteins, allow detect different smells or different odorant molecules. So there are genes that have been duplicated in evolution, which continue to function and genes that were duplicated and do not work more, which are pseudogenes. Yeah? So In summary, to close this part, DNA repetitive, yes? It can be very repetitive in tandem, yes? Like the satellites of the centromeres, the min satellites of the steromes and the mycosellites, which these two are used as genetic fingerprinting in forensic genetics and filiation. And we have repetitions scattered, yes?, which are much more larger than those in tandem, they are much more repeated than the tandem ones, which are the lines and signs, the retrotransposons, No? And the DNA transposons that are missing here. Okay, so taking out the Mitochondrial DNA, in the human genome I have the nuclear genome, right? Have sequences that are eh genes, right? the coding portions, sexons and non-coding sequences such as introns, regulatory sequences, yes, pseudogenes and non-gene DNA, which nothing to do with it, they are the sequences repeated. Yes, just like until now then understood everything correctly, Mao. Yes all ok. Yes ok. Jewel, eh, even here then the part of eh genome human, generalities that we had to see, yes? There is a small part left of eh mutations that if you want we can talk or we cut here and we see it later or we tell you I record as you prefer. Not to be very burned or more or how it is. Hey, whatever. I I I can. As you wish. Do you want that? let's continue? Should we continue or leave it here? As you prefer. Yes, yes, I don't have problem. Yes. Well, I'll try to do it. as fast as I can. Basically we are going to see what there is tiny mutations, micromutations, Yeah? that can alter a single gene and cause genetic pathologies or diseases monogenic. Yeah? And let's see what there is macromutations, large mutations that affect a piece of chromosome and therefore both to hundreds or thousands of genes and cause pathologies and abnormalities chromosomal, so they are different. So let's think that a gene is a unit of information, the basic unit of inheritance. Yeah? These genes are can study with biology techniques molecular like PCR, sequencing and such. And we are going to see that chromosomes are the unit of how DNA is organized. Are like the volumes of books, right? I mean, from a library. Chromosomes contain a lot of genes. It's like that organizes DNA. Those chromosomes eh la discipline that studies chromosomes is cytogenetics. Let's see more forward in the techniques we use to analyze chromosomes and and anomalies chromosomal. So here we have the DNA, right? With histas that folds and forming chromosomes, right?, which is what that we talked about before. After the thing about human genome that I told you about in 2001, 2003 around there that I know that it was known human genome, barbaric, all very happy. A study was then made in 2015 which was published to analyze the variability that existed in the sequences. Yes, a very very study large with 26 towns. Yes, it was analyzed the human germ of 2,500 people. Yes. And what was discovered is that if I I grab two random people, Yeah? They share their human genome in a 99.999%. That is, they share a lot of DNA. Each of us shares a bowl. Then there will be subtle differences small DNA, 0.001% difference between people and that is how they vary in each person randomly or between different people ethnic groups or different regions, Asia, Africa, Europe, blah blah. Eh, but in general we are all one 99.999% genetically identical. Yes. And the The difference is more or less 3 4 millions of nucleotides. Let's see how these are generated differences that are due to mutations basically, right? So, the Mutations are defined as changes that are permanent in the sequence of nucleotides. Yes, it is a permanent change that can no longer be repaired by the cell, which was fixed there, right? And may or may not have an effect on the cell may not generate any flaw. Maybe we can talk about mutations at different levels, different sizes. A mutation at the level molecular, a tiny mutation. that affects a few base pairs or 1000 base pairs. We talk about micromutations that can affect a single gene. Yes, for example, here you see that This base pair is replaced by another, changes one base for another. So, it's called base substitution. This is a sequence that affects a single base pair. It's a mutation tiny, a micromutation and yes well this may not be the case mutations are bad. Always sometimes one thinks about mutants, mutations are a bad thing. In In reality, the mutation may not have no effect, which may be a mutation advantageous to the individual who I gave him an advantage or it may be one disadvantageous mutation that gives you a monogenic single-gene disease, No? Or that predisposes you to get sick, No? You're bound to get sick. And there is larger mutations affecting thousands or millions of base pairs that affect mutations that alter a segment, a piece of chromosome and a many genes, which are abnormalities chromosomal eh previously called chromosomal disorders, which are macromutations, large mutations. By example, here you see that a piece of chromosome is lost, there is a deletion of a chromosome, the chromosome is more short or a segment of chromosome that is doubled. That alters hundreds or thousands of genes, yes? and generate pathologies in more serious general. So, the micromutations can be detected with molecular biology techniques, techniques to be able to analyze small portions DNA tests such as PCR, No? So, and we'll see more techniques in the classroom following. So these mutations they can occur both in somatic cells, which They are the cells of my body, which are not gametes, or germ cells, which They are the gamete-producing cells. Yes. For example, come here, I have here two gametes that fertilize to form the zygote, the egg cell. This zygote begins to divide, divide, to divide and at a given moment originate stem cells that are going to divide to give rise to all the cells in my body, that are not gametes and a line of cells that will produce the gametes, spermatozoa, eggs, No? What will happen if a mutation is already It comes from my dad's gamete or my gamete. mother? Where will it be? mutation? In me, in my whole body, in part of me body. What do you seems? If I a mutation from the gametes from the father, then the mutation is already present in the zygote. The cell egg at the time of being fertilized has a mutation, a DNA change. Is that mutation going to be everywhere? body or not? Uh, yeah. And the father's inheritance, right? Because if it's a guy, I don't know if I understood wrong. what you said, but if she is a woman she doesn't have one, doesn't have one, well, but it doesn't matter. Okay, But that's what you say, it's in the chromosome sexual, but to put it that it is in another chromosome that is neither X nor I and in any Ah, okay, okay. No, in anything, it wouldn't be in everything. Hey, actually if it is from the gametes, yes, because imagine if my dad or my Mom transmits to me an alteration, a DNA change, a mutation, right? Then they fertilize, the zygote begins life with that DNA change, right? He zygote divides and by mitosis, by division, gives rise to all cells my body. Videl zygote. All, skin, pancreas, liver, brain, gametes. All cells derive from division of the zygote. So, did you see that I I said that all cells are equal genetically? So if the zygote has a mutation inherited from someone father, when it divides, that mutation goes to be present in all cells, both somatic and gametic. HE understand? Yes, that's where it was understood. Or it may be that the gametes are normal and fertilize and have a normal zygote, but beginning of embryo development, in the first divisions of the embryo, the first cegulitas mothers mutate by errors in duplication or that was, at the beginning of development early bronarius there is a mutation. There is the same before the differentiation cells, tissues. Eh, when that cell divides, the mutation will be present in all the cells of my body and how it affects cells somatic, the cells of my organs, I get sick, that is, I show symptoms of a pathology. And if the mutation It is also present in gametes, that gamete can participate in the new fertilization and I can pass it on to you a mutation to my offspring, to my children. If the mutation is in gametes, It's not going to affect me and I'm going to be able to do it. inherit the mutation and that's how things are done heritable diseases, are they understand? Eh, but well, that's for a side. Another example, another case, the gametes are normal, fertilized, sygote normal, barbaric, it begins to divide, the stem cells that are already differentiated give rise to gametes and stem cells that give rise to somatic cells. They are all the other tissues, pancreas, liver, lung, everything, right? Good. And somatic cells mutate during the embryo development or mutate adult, let's say. I, for example, let's suppose that now I always put this example to make it clear. No I know, I get 85 hours of sun a day without protection, without sunscreen and and pu I am more predisposed to lightning from the sun damaging my skin cells, from my piemis, it damages DNA, you know? DNA, the sun's rays. So that cell of my skin that suffers a mutation by sun ray, to dividing will give rise to cells of the mutated skin too, but that's not all over my body. I mean, there's going to be other cells of my skin, of others parts of my skin that do not have the mutation, right? And other cells of me body, pancreas, liver, heart, which no, it doesn't have the same mutation either. As the tissues are already differentiated, already I have two tissues that were monitored. that are different. If I have one mutation in a tissue, that mutation affects not only part of the cells, but also all of my body, you understand? So, I'm going to have symptoms of it. damaged organ, but not all of my organs. But well, when there is mutation in somatic cells, this is manifested in the person who has the mutation, No? I have, for example, damage to the skin, I'm going to have a symptom in the skin, but since that mutation is not present in my gametes, because by example that the sun's rays damage my skin, does not mean that they damage my Sperm, for example, does not have nothing to do with it because they are stem cells different, everything different, they are already there differentiated. So if my gametes They don't have that mutation, I'm not going to inherit it. the mutation to me to my offspring. By That's what I'm saying, most cancers are not inheritable. Do you understand? I have a skin cancer because the sun damaged me the skin and if that mutation is not in my gametes, I'm not going to pass it on to my children. It is understood that the mutation in somatic cells affect the person, but it is not inheritable to offspring if the mutation is not present in gametes. We're doing well with this, maso. Yes. And there are cancers that are heritable. Yes, there are some cancers that do. Hey, what? for example most cancers, We will see in the last class of the Once this is completed, most cancers are are due to mutations in many genes different that doesn't make you sick yes or yes, which increase the risk that you get sick or lower your risk get sick, but then it influences the atmosphere. Obviously, if I smoke, eh, No, eh, I don't know the ones that I environmental pollution, things like that e eh what do I do, I don't know, what do I smoke, what do I do exercise, food, all that stuff. But there are some cancers that are due to a single mutated gene, monogenic cancers, No? That if you have that mutation you have a high risk of cancer, No? Uh, for example, breast cancer or some colon cancers, for example, It is known that there are very few genes that can cause. Yes. Uh, so what and what You study a family and there are several cases in the family, for example, for that reason. Hey, but if. Okay, sir, thank you. No, nothing, We will see in the last class or one of the last classes of the completed when we see oncogenetics and we question well with this, right? If instead I change them now eh the example, if the mutation occurs in germ cells, in stem cells that produce kites, right? Let's suppose that now at random my stem cells that that divide to make cells They have an error in the division and I have a mutation, a DNA damage. Well, that mutation will be present in some of my gametes and others not. So, it depends on which gamete is fertilized, I Can I pass the mutation on to my child or No. But if the mutation is in gametes, It is inheritable to the offspring of that person mutation, obviously. But like that mutation that is in my sperm, by example, it is not present in my cells somatic, you understand? If the cells mother have a mistake and and my gametes mutate, it does not mean that that mutation is in my liver or in my brain. So, mutations in gametes do not cause, do not manifest in the phenotype of the person who carries the mutation. The person is asymptomatic, is carrier, do you understand? If I have a damage to my gametes, I don't understand, no I have a defect in some organ, in some other organ, because as they are already differentiated tissues, right? Hey, it's not happening. nothing, basically, I mean, nothing happens. Yes, the mutation is heritable, it is transmissible to offspring, but not I get sick, I don't even realize what or what I have the mutation, if it is not affected my somatic cells. So, for that a mutation generates a manifestation in the person, they have that the somatic cells are mutated, the cells of the body, which are not gametes. Yes, if they are mutated gametes, that does not generate a phenotype, a appearance of symptoms. Yeah. And vice versa, so that the mutation is heritable, transmissible to the offspring, the mutation has to be in gametes. If not in gametes, it is not inheritable. It was understood up to here. So, this is more or less it. Yes. I have a question, I can't finish. to understand, that is, to put if I receive from my mother a mutation that she had in its germ cell, there I am grabs on to the zygote, right? And I have a type one mutation. Yes, if you inherit a mutation from your Mom, since that mutation is already present in the zygote and like all cells of my body, well of the zygote, that is, is a single cell that divides and originates all the cells in my body. So all the cells in my body are going to have the mutation, all of them. Okay. But my mom does not have the symptoms. Sure, if it's in my mom's gamete only she doesn't It's going to be no, it's not going to be sick, I don't know is going to find out. Clear. Exactly. By that there may be healthy parents with children sick, right? And the bigger it is one, when there are great, great parents, big, eh has a higher risk of having sperm mutations, right? Because the bigger one is, the more mutations we accumulate the more we grow old. So, of course, that could be. Oh, sorry. No, calm down, calm down. That when putting a sperm has two tails or no tail or two heads. Yes, that's also why. Yeah, also. But that would be a mutation that then it is inherited by the son. Clear. Yeah. It's those spatozoids that are actually those defective husbandoids maybe not no can fertilize. Yes, but if there is one mutation in the DNA of the gametes that It happens out of nowhere, eh the person who carries the mutation does not realize it because it does not their somatic tissues are mutated. So the person is healthy, but that mutation is inherited by the child, the child inherits it has it all over his body and the son does shows symptoms and becomes ill. That's why There are healthy parents and sick children. Unclear. Exactly. There is nothing. No then confuse somatic cells with autosomal chromosomes or autosomes that always confusing. There are two things different. Yes. Somatic cells are the cells in my body that are not gametes. And the autosomes are the chromosomes of pair 22 or the first 4 44 chromosomes. Yes. The chromosomes that do not are sexual. It is not the same as me saying that there is a mutation in somatic blindness. It does not mean that it is mutated autosome, an autosomal chromosome. By example, it may be mutated into a my skin cell the X chromosome. Yes, it is a sex chromosome, but it's in me skin because my cells have 46 chromosomes, they have 20-22 pairs of autosomes and a sexual pair. That is, all of them My cells have sex chromosomes and autosomal chromosomes. Do I make myself clear? So, it could be that the rays of the sun that hits my skin make a mutation in my X microsome, by example, right? So, this, this association is broken. And do not confuse either germ cells with chromosomes sexual, because it is a germ cell, a stem cell that produces gametes, not It means that it only has chromosomes sexual, also has chromosomes autosomal. That's why I'm from parents to children would be 23 chromosomes, half of chromosomes. Imagine if the cell germ line had only chromosomes sexual, I would pass on to my son a only chromosome instead of 23. So, the difference between gametes and cells somatic is not that somatic has only autosomes and gametes have only sex chromosomes. Both have the two types. The difference is that the somatic cells have 46 chromosomes, chromosomes of pairs and gametes They end up having half, 23 chromosomes. They are aploid cells instead of diploids. But it could happen that in a gamete has an autosomal chromosome mutated. No, no, no. It could happen, yes, eh, that a mutation, autosome is transmitted to offspring by gametes. So this association is broken. Yeah was it understood? This happened. Yes. Yes. Well, watch out for that. Here we are difference. See that both gametes, spermatozoon and/or cell diploid, a zygote or any cell of my body, both cells have autosomal chromosomes pair 1 to 22, Yeah? And sex chromosomes or X or I. Yes. But the difference is that the gametes They have 23 chromosomes, one chromosome per pair and somatic cells have paired chromosomes, right? 46 chromosomes. So watch out for that. Can pass, as I said, as I told you with the cells of my skin, that if I suffer damage to a cell in my skin by the sun, is the mutated cell divides and It creates mutated daughter cells, right? And it goes to have other cells in my skin that be normal, right? And other cells of my body, of other tissues that are normal. When I have in my body some cells without mutation and others mutated cells, we say that there are mosaicism, in this case mosaicism somatic. That is, somatic cells that I have some normal ones, others mutated, Yeah? Eh, or that the person is a mosaic It is called well, which is made by cells of both types, mutated and not mutated. Well, and also, for example, that can happen in the adult, as I told you, by ray of the sun or at the beginning of the embryo development. They see that the gametes fertilize and are not mutated. The gametes of my parents, the zygote, the egg cell is normal. It begins to divide the first divisions of the embryo and a cell mutates out of nowhere spontaneously. So, the cells normal, normal stem cells embryo give rise to normal cells. The mutated cells give rise to cells mutated, right? So, I'm going to have like patches like some cells of my mutant body and other cells of my normal body. I am a mosaic. There is a mosaicism. Yeah. And the earlier it occurs in the pronary development, eh, the mutation, yes, more cells affect, because, for example, the cells, the zygote and the first cells of the embryo originate all my body. Well, a little more advanced, embryo development, give rise to less cells. That is, the more you advance the development of the embryo, the cells mother cells give rise to fewer daughter cells, which This is what we saw or what I recorded in class. of differentiation. For example, there are cells in the embryo that They originate skin and neurons and not others fabrics. Yeah? Uh, so if I have one mutation there, I'm going to have a mutation in my skin and my neurons and not in others organs. But if the mutation occurs more early embryo development, affect many different organs, are they understand? That is, the earlier is the mutation, more tissues are affected, because stem cells are not yet differentiated and can originate many different organs. Basically, while Later in development occurs mutation, when they are already differentiating the different tissues are less affected number of cells. Well, but there are also mosaicisms germ cells, it may be that stem cells of gametes mutate and then originate some normal gametes and other gametes mutated. If there is a germline mosaicism there. So it depends on which gamete fertilize, whether the normal or the mutated, I I will pass the mutation on to my son or not. It is understood, I have both odds. So far so good with the mosaicisms. Do you understand? Yes. Good, perfect. That's what we were saying before. There may be a father who has some gametes mutated, others normal, he doesn't understand. How will it be mutated? somatic cells, is a healthy person and when the mutated gamete is fertilized, the child Yes, he gets sick because he has the mutation throughout his body. Yes. This is called de novo mutations or Nobel mutations or new mutations. Yes. It's not that the father has the mutation in all his body, has a genetic disease and the son also reads it. The healthy father has some new mutations of the nothing in their gametes. Yes, it is a mutation again well. When gametes occur parents or early in development it's the same, mutations of no. Yes ok. Question. These mutations could be repaired in principle by different repair mechanisms that we have in the cell. Good. So, changes in DNA, changes in the nucleotide sequence of DNA are genetic changes, mutations, right? No epigenetic changes, as we saw in biology before, which were changes that did not altered the sequence of bases of DNA. That's an epigenetic change. A genetic change, a mutation is when if the base sequence is altered DNA. These changes are in principle susceptible to repair. can be repaired in principle within a cell cycle, for example, are called premutations or changes premutational. When the mechanisms repair shops do not recognize an error and do not They repair it and the cell divides and passes the mutation to the daughter cells, that change is already indistinguishable, it cannot be recognize more, you can't repair more and It remains as a fixed mutation, not as a premutation. Yes, so far so good. this. All good? Yes ok. So why are they caused? mutations? It may be due to errors during DNA replication. Errors that causes DNA polymerase when it copies DNA in S phase. In replication can make mistakes and introduce mutations. They can be changes spontaneous events that occur in the nothingness of the nothing outside of replication. By example, the bases of DNA, the bases nitrogenous, cytosines, guanines, thymines, can suddenly lose some some molecules or atoms and and undergo spontaneous mutations or may there are changes induced by agents mutagenic or mutagenic, by agents that cause mutations, which induce mutations, for example, radiation from sun or X-rays, eh chemical agents that There is in makeup, in products ultra-processed foods or the cigarette, in cigarette smoke. or eh infectious agents like viruses oobacteria can induce mutations. Yeah? So, for example, changes spontaneous that can induce errors in DNA replication they can be because the geometry changed, 3D structure of DNA. It may be, for example, by radiation from the sun, which the DNA has a rare shape or shapes out of nothing that has DNA. Can do that the polymerase makes mistakes, confuse and lay down bases that generally do not They are complementary due to their unusual shape of DNA, now they are complementary. Yeah? Or there may be rare forms of the nitrogenous bases, of cytin, guanine, thymine, right? From the bases of the DNA. They can be forms, there may be rare forms that are called tautomeric that also cause damage or errors in replication. Yes, tautomers are eh variants of the DNA bases, right? What are the bases are the same bases, but with a different chemical structure, Yeah? Because? Because they are rearranged electrons and protons and changes shape. For example, this is a base of adenine, the base of A, in DNA. See that This is the original base or the sorry, the base the shape that predominates in the cell normally. This is a rare form, a little changed. has the same amount of atoms and everything, but it's a little changed shape. The same with the guanine, yes? With thymine, with cytokine. I have bases that have a predominant form and sometimes out of nowhere some base, he is crazy about almonium, he rearrange the electrons and change the chemical form of the base. It's a tautomer as a variant of the base. Yeah? So most of the time certain natural bases predominate normal ones that we usually see. It may be that out of nowhere the base changes shape and that base changed in a strange way have complementarity with bases that naturally I wouldn't have complementarity. For example, they know that you know that adenine always it joins with thymine, a with t. When there is a tautomer, when there's a strange thymine, right? That rare thymine may have affinity for guanine because it changed its shape electrons, everything and can fit like a puzzle with guanine. That's a problem because this shouldn't be so, let's say, right? Or for example, here in Instead of having CG I have AC because there is a eh a ta automeric base. So these weird shapes, right? For example, here during DNA duplication I have this template, the DNA template strand, yes it is used to copy a daughter strand new by DNA polymerase. So, If I read, for example, an A in the mold, I would have to put complementary to T, naturally, right? Well, here I have a rare citcina, a tautomer, a cytosine that changed from chemical form and changed shape spontaneously and is complementary, has affinity for adenine. So, the polymerase says, "Hey, this piece of puzzle fits well, I put it, ready, he came in." Then he doesn't realize and puts one rare cytkin linked to an A, non-cytokine from Nina, that this shouldn't happen. What's happening? That rare citcine of the tautoeric of nothingness can return to its original form its predominant form. It can rearrange its electrons turn and return to the most common form. Do you understand? So, when changing from form again ceases to be complementary C to because they are the bases fit well the A with the T, the C, because it fits into its 3D shapes like puzzle. Yes, if this weird base returns to form original, the situation and adenine They lose affinity, they are no longer related. Yeah. They are not like puzzles that do not fit together. Polymerases, DNA polymerases that copy DNA have the ability to recognize that the last opposite nucleotide is incorrect. They could cut it, eliminate it. Yes, it is. they remove it and put a correct one. Good, has an activity called reading of tests or in English proof reading. Yes, it has exonucleic activity, some DNA polymerases. What do you want? say? That they can check that if the last nucleotide does not bind to the template, no the mold is matched because it is not no fits. Yes. He cuts it and puts a correct nucleotide, the polymerase is It is self-correcting, it is understood, As the polymerase duplicates, it can self-correct and cut the last one nucleotide you put if it is incorrect. This is this error where A and C do not match is called mismatching bases. In English mismatch, yes? So, it may be that at one point an inorganic base changes its form chemistry, fit well with a mold, which naturally it would not fit, and when return to the original shape and peel off from the mold. If it is the last nucleotide position, the polymerase can cut it and put the correct nucleotide. Now It may be that that strange base was left fitted into the mold. It fits well, it is be weird with the A. The controversy continues doubling down, keeps laying new foundations, so if this is this strange base returns to its original shape and peels off from the mold and then the duplication followed, polymerase can't return for a long time back, that is, break many things and return. That error is now fixed, Let's say, yes, there is the DNA detached from some part deformed. So, the errors that the polymerase cannot repair with that reading of evidence is repaired by another mechanism that now I show them. Yeah? So, reading Testing is an activity that has some DNA piles when duplicate, it is because it has activity of exonuclease, which can cut the last incorrect nucleotide and put the correct when not paired with the mold, when there is a bad pairing. Yeah? So this happens during the S phase, the cell cycle, that is, As the polymerase copies the DNA, it can self-correct. If those errors, as I told you, I showed you recently, they occur after the end of the duplication, for example, or when the Polmeraza continued, an error occurs new, a bad pairing. See that This base, this G, is not complementary the T, right? Maybe there was one, it was a G rare that at the time it was complementary, but upon returning to the original form is no longer complementary the G with the T never is. Then the DNA is deformed, you see? As it is separated, as there is no union, the DNA has something like this little belly. So This is the 3D deformation of DNA. recognized. Yeah? and we're going to eh proteins that they are going to cut a large segment of DNA to have a certain margin of error, to say I think he is here mistake. Then they cut a segment large by nucleas, is replaced, DNA is filled by a polymerase and seals the space by an enzyme that is called ligase, which seals the new strand with the correct nucleotide. This repair mechanism that repairs the base pairing mismatches that could not Correcting the polymer itself is called repair due to poor base pairing. They killed themselves with the name, didn't they? The abbreviation is the rheum of this mechanism. Then repair the evils fittings, yes?, of the two strands of DNA that was not repaired by the polymerase. And this happens at the end of the duplication, at the end of S phase check that there is no error in DNA duplication, right? If I know if I know finds an error, the points are activated of control, remember? The cycle cellular, the cycle is stopped, it is activated This DNA repair mechanism and repairs. Yes. And it can also happen when beginning of the next stage, beginning of G2. Perón, was it understood what is what's going on here? or how this mechanism repairs what the former did not repair other former. Mao, yes, maso. Yes, yes. What is the topic? I I have that the AD is deformed because the, For example, G with T are not complementary, they are bases that do not usually go together. So, since they don't join together, Hey, the DNA is a little bit distorted, isn't it? There is no union, the DNA remains detached. Well, how do I recognize that there is something to be done? cut here and not the mold? I mean, how? How does DNA taste? Because I could take out, how do I know which is the mold strand and the daughter thread? I could take out the G and put an A, put AT, right? What would it be? normal, correct. Or I could take out the T and put a C, which is also C and G are complementary, aren't they? I would be well, supposedly, but it would be nothing to see the original sequence. So, to correct the eh the proteins have to recognize which one is the newly manufactured strand that suffered the mistake. Yes. So that they do not harm without want the mold. So, for correct well, there are several mechanisms to know which is the mold strand in the that there is no need to act and what is the thread new, which is the one that does need to be repaired. On the one hand, the mold strand is methylated. Do you remember methylation? of DNA that we saw in epigenetics? Well, the newly stranded DNA strand manufactured, recently copied, not yet is methylated. So, I can say, "Ah, this is the thread, let's cut it this." And also the daughter thread, the thread of newly manufactured DNA, has spaces empty spaces between the mold doesn't have. What is this hollow space? RNA primers. When we speak a slightly above DNA replication, We talked about how to start copying DNA, I have to make a chain short RNA, a primer or sear for start duplication. that short chain of RNA is then removed and refilled with DNA, right? If it has not been filled out yet the space, here I say, "Hey, this space empty is because there was a first of here RNA." So this is the newly manufactured. Let's cut this one and repair it. And we are not going to, we are not going to cut the mold because sometimes it could happen that, that the mold is cut without wanting that should not be cut. But Well, this is the way in which this mechanism recognizes the newly strand manufactured, repair that thread, okay? and fixes replication errors of DNA and these and the proteins of this repair mechanism, know that, see, all the proteins that repair the DNA, its genes are suppressor genes tumors, right? Because they are avoiding the accumulation of mutations. Do you remember? of this classification of genes of proto-elevenses and suppressor genes tumors? Well, if these genes that repair mutations, these genes are mutated, the genes of the proteins of This mechanism of repair, eh, which are suppressor genes tumors, if these genes do not work well and this mechanism does not work repair, for example, can colon cancer may occur this repair mechanism. Yeah? Well, we see the same thing here. We see here that I have a template DNA strand. I separate the two strands, each one is a mold for make the new daughter strand. Yeah. If I have unintentionally a tautomeric basis, a basis that changed in a strange chemical way, it is complementary without creating with latimine. This weird base, it shouldn't happen that There is GT, right? You see it here. And this is it mold strand is normal, everything normal. Well, question. When this is if this is error is not repaired, it is not corrected or even reading of proofs nor for evil base pairing, when there is a new DNA duplication, I separate the two strands, where I read where I see a G, I put a C in the new daughter thread. And in the other strand, where I read a T in the mold, I put an A in the new DNA. So, I now have two strands. of two DNA molecules, one normal and one a mutant. It is not right that the air t are complementary, but it has nothing to do with it to the original sequence that had to be be GC. So these errors remained fixed. The cell no longer recognizes that this is wrong. The cell doesn't say, "Hey, No, this is an A and a T, it's wrong. There should be a CG." At first. This error is fixed, is that understood? I have a premutation that in beginning within a cell cycle can be corrected. When cells They divide into daughter cells, and that error is unrecognizable to the cell. He doesn't realize that it's a mistake and it remains as a fixed mutation. In this case, see that we change a pair of bases for other. This is a substitution, the change from one base to another. Yeah? We're doing well more or less with how they are fixed errors after duplication. Yes all ok. Passed good. There are also spontaneous changes that have nothing to do with duplication of DNA in the inrogenated bases, by example, it may be that here I have a nucleotide, a phosphate, the sugar and the nitrogenous base. Sometimes out of nowhere the nucleotide may lose its base. For example, I have sugar, phosphate, guanine, guanine flies out, it lose out of nowhere, flies away, breaks the union. That a nucleotide follows a base, do you understand? uncleotide eh orphan without base nitrogenous. This is called depurination because a purine is lost. The guaranine is classified as a purine. EITHER It may happen that an introgenated base, Here I have the base of adenine, the a of DNA, lose a molecule, right? A couple of atoms are lost from nothing. Yes, that is called deamination. When you lose a amino group this nitrogen molecule, nitrogen hydrogen, it doesn't matter, but it What you have to show them is that they can missing complete bases. or some base molecules spontaneously. Yeah? With which this mechanism is going to be This error is going to be recognized, these chemical damage out of nowhere by eh base excision repair. Esición esir means to cut. Yeah? The decision of bases or reva is a mechanism that repairs spontaneous damage chemicals in the bases. For example, when the citina lose a molecule out of nowhere, right? This molecule is the same as uracil. RNA, yes? That is, out of nowhere he loses a molecule, it is transformed into uracil and No, I can't have a uracil, a RNA base in the middle of the DNA. So this incorrect nucleotide, This base is removed, the nucleotide, sugar and phosphate, and replaces only that nucleotide. It is put a single correct nucleotide, replaces one base with another. Yeah? This It is the decision-making mechanism of bases. Good. I'm repairing spontaneous damage that changes the chemical structure of the bases and how this damage can occur in any time in the cell cycle, This mechanism can correct errors in any time of the G1, S interface, G2, at any time during the cycle cell phone can correct this. Look, Here I have a rare citina that suffered damages. sugar is eliminated, the phosphate, the nucleotide and a is placed correct nucleotide. So, this mechanism repairs damage that affects a single base. Yeah? Now, there may be damage that affect many nitrogenous bases in DNA and can be mutations caused by mutagenic agents, induced mutations. For example, there are mutations induced by physical agents like radiation, right? Ionizing and Non-ionizing are, for example, X-rays of X-rays. Yes, the X-rays can cause rupture in the DNA double helix, that is, they break the two strands of DNA. It doesn't mean because I get an x-ray or a CT scan is going to make me die, but if you do a lot, that is, you would have to take many x-rays a day and per year to have a mutation, right? and have cancer, for example, but clearly increases the risk, doesn't it? So, X-rays can do damage in the double strand of DNA. Also the gamma rays or cosmic rays that are in the space, that some arrive here eh to through the atmosphere and harm us and more astronauts still suffer radiations eh suffer, sorry, exposure to radiation that can damage your DNA. And also the V-rays of the Sun can make two bases of the same DNA chain join together, something that should never happen. Yes, now I'm going to show you this. There is also chemical agents such as some acids such as nitrous acids or agents that They are called alkylating agents which are also dangerous. Or benzene, which is a compound that is a compound very dangerous carcinogen that is in the cigarette smoke, in the smoke of the cars, eh in a lot of places further. can cause damage to the system nervous, cause blood damage, cause blood cancer. Yes. And here I have some eh examples, for example, substances in cigarettes that are toxic, such as nitrosamines, which is a known carcinogen, such as benzene, which I told you about just now, like the cetyl aldehyde, yes? Hey, nicotine. It can also cause mutations in the DNA. So, there are a lot of agents chemical and physical that can cause mutations. Yes. And many more. also biological agents, bacteria, for example, this bacteria that causes stomach ulcers, Helicobacter Pilor, this bacteria can induce an inflammatory environment inflammatory. This causes damage to the mitochondria and metabolic problems in cells or substances that oxidize cells and cause mutations in the DNA. Yeah? Or viruses the same. By example, the HPV virus that infects the endometrial cells, right? of of and of the cervix. This virus can alter the cell cycle of cells because it alters, causes mutations and alters the proteins that regulate the cycle cellular and can cause cervical cancer of the uterus or the hepatitis B virus that can infect the liver and cause cancer of the liver because it generates mutations, right? And also the virus that affects the lymphocytes of the blood cells whites, right? of our defense, the rubiola and the sarcope 2 virus, the virus that causes COVID-19. We also know that it causes DNA damage and mutations. Yes, there is also fungi that cause mutations and how to We saw before, the genetic elements that jump, the retrotransposons, could jump, get between a gene and alter a gene and cause mutations. Is rare, but it could happen. Yes, these are biological agents that cause mutations, right? More chemical agents we have, for example, I have not heard name the topic of asbestos, which is used for example, for the plates of the roofs and for eh we have in the in the subway cars or rails of our subtests, we have this substance that is banned in almost everyone, except here. Hey, these substances chemicals may not break down with the heat or anything, they are inhaled, they are inhale, accumulate in the lung and do not They can degrade over the years can end up causing cancer lung these substances. Obviously that you have to be exposed for a long time, It depends on how exposed you are, distance, right? But the workers of the subway, for example, perhaps not to the another day, but after 30 years of work They start with lung cancer, that is, they It gradually accumulates little by little and damaging little by little, right? There are a lot of chemical agents in foods, artificial colors, flavorings, deodorants, uh, preservatives, plastics, yes, they are in a lot of sides. Hey, now I've heard of it. also of substances such as paravenos, thalates, biphenol, benopyrenes, a bunch of substances that They are in the makeup, a lot of sides eh that are the cause of mutations. Yes. For example, the sausages that also have a lot of mutagenic agents. Hey, plastic bottles, right? The make up them makeup, sunscreens or body creams too, because these chemicals or plastics are can be inhaled or absorbed by skin as well and cause mutations. It Same with perfumes, right? they can absorbed through the skin, they travel through the blood flow to the entire body and can cause mutations. With this no you have to be paranoid and not get nothing, but be cautious and look for, example, eh products that say without paravenous, without biphenol, yes, without effalates and search for compounds such as more and the least harmful possible, let's say, right? Or instead of using a bottle plastic, glass bottle. And there is a a couple of things one can do, right? AND Many of these substances are called endocrine disruptors because they can alter the metabolism, the system nervous, yeah? Eh, you can eh try to mimic natural hormones and interfere with the body's normal metabolism. Lots of toys and colors that They use them in toys, eh, they are absorbed by the child when he eats them. Are plastics that can cause problems to long term. Yes. The colorants of the of the snacks, which we all love so much, I love them, but well, Unfortunately they have a lot of substances eh mutagenic and the plastic that is in everywhere basically in paintings, aerosols, yes, in cables, in what do I know, everywhere basically. And a lot I had heard of haban heard about pesticides and such, There are a lot of chemicals that can damage DNA. And for example, Going back to what I told you about rays of the sun, we can see that when there is many thymines in a row in the same thread, here I have tt, for example, right? Ta, when there are two thymines in a row in the same strand, due to the effect of the solar radiation, they can join together, which never happens. Do you understand? Between the two strands of DNA the bases. The bases of the never join same strand. They are joined in the same strand phosphates and sugars. So, the rays of the sun cause two thymines in a row unite and lose union with each other strand, which is why DNA is deformed. Yeah, 3D. Uh, this is called thymine dimers. or dimers of pyrimidines. So, by recognizing each other that the AD is deformed, its structure 3D, there is a repair mechanism that It is the decision of nucleotides, which repairs damage affecting many bases, many nucleotides. Yes. For example here that affects two. Then it cuts off a large segment by nucleas, removes this entire mutated segment, filled with DNA, by a polymerase and is seals the space with a ligature. Yeah? So they affect and repair damages that affect several bases. Yes. For example, the sun rises by lightning. Here we see that the same strand sugars are normally joined together and phosphates and here they join eh the bases that shouldn't happen. Yes. That DNA, that Damaged DNA, rigid, eh, does not allow the correct DNA duplication, transcription and so on. So, this DNA separated from the template joined together, a large segment is cut and filled and it is sealed. Okay, here's an animation. Let them see how the sun's rays make the union between two bases of the same strand. Yeah? The decision mechanism is activated nucleotides, the cell cycle is stopped, No? The mechanism is activated, cuts, fill and seal. something very similar happens in all repair mechanisms, No? But well, these eh this can occur at any time during the cycle cellular and its proteins repair mechanism, if they are mutated genes, it can occur skin cancer, yes? Or a type of genetic diseases that cause sun sensitivity and skin cancer. Obviously, if the mechanism of this repair doesn't work, I accumulate errors, mutations by the sun's rays that do not are repaired and the accumulation of damage in skin ures cause cancer fur. Yes ok. And finally, there may be eh damage to both strands of DNA at the same time time, not in a single strand. And those cuts of the two strands activate double-strand repair mechanism, that we talked about when we saw the edition genetics by Cris Parcas, which is the repair by joining ends homologous or repair by homologous recombination. The first This mechanism repairs badly, it repairs error-prone, prone to err. For example, when there is a cutting of the double strand of DNA spontaneously or by X-ray or some people who induce such damage, there are bases nitrogenous, DNA bases that come out flying, they get lost. For example, there may be loss of nucleotides. This repair mechanism what it does is seal the tips without filling, that is missing, it cannot be repaired with a mold, but just glue the tips together and that's it. AND I have a much shorter DNA than what It was before, wasn't it? I have a lesion, I have a loss of nucleotides, of bases, yes? Or there may be bases of the nothing that is added unintentionally, inserts, but hey, this can generate small changes or at the level of a chromosome that you are missing a piece of chromosome, basically understood as repairs without a mold, seals the ends uh, sorry, yes, seal without filling and damaged DNA remains. And this mechanism can act throughout the cell cycle, basically, mainly in G1 and It also acts outside the cycle in G0. But if there is a mold, there is a mold nearby that I can use to repair it damaged, for example, after duplication from DNA, I have this little leg of chromosome, this chromatid and the duplicated DNA molecule, then duplication, after S phase, I have the sister chromatid, a molecule identical, an identical copy of this DNA sequence. Well, if it gets damaged one, I can use the other as a mold for replace it with a damaged one. This repairs a lot better. Yes, much more verbose, let's say. EITHER If there is a homologous chromosome nearby, for example For example, my chromosome one breaks. Dad, I use mom's chromosome one as mold to replace to fill it damaged from the other, right? And there is one homologous recombination. This mechanism repair it well, eh? And acts as required from a mold, acts after the DNA duplication, right? After S phase in G2, right? So this mechanism repairs half, just like that, it repairs poorly. And this mechanism Since it uses a mold, it repairs well, basically and acts in phase S, eh, acts in G2, sorry. Good. And this mechanism of repair, the genes, when it is mutated the repair mechanism, when your genes are not working well, which are These genes, eh, are superior genes of tumors, obviously, and they can cause cancer from breast. Yes, these gels are called braca, which in English means brecer, breast cancer. And it was discovered that these genes when mutated do not They repair damage, damage accumulates and that's it causes breast cancer. It is a type of hereditary breast cancer that I don't know who had asked me before, but can study if there is in the family mutations in these genes to find out if you are at risk of having breast cancer or No. Yes ok. Have you understood then? DNA repair mechanism more or less less? Passed. Yes all ok. Yes. Does anyone have any doubt? Was it understood how each works? one? What are you fixing, that we are not doing well? Yes, yes, spectacular. Well, up to here let's leave this. This is the scientist who discovered these genes, which is Mary Cler King, which is a English scientist. He also discovered that we humors and chimpanzees are eh almost 100% identical genetically, that is, It is a very thick mine. And he discovered an eh or generated tools for testing of affiliation, right? analyzing DNA in the mitochondria, being able to see them DNA similarities between grandmothers when parents are missing. For example, in dictatorships, in the Argentine dictatorship, who have kidnapped eh fathers, mothers and The children were left without their parents because connect these missing children with their grandparents through techniques of forensic genetics, right? That's what they do dictatorships. This girl, this doctor, worked in Argentina also and separately discovered these genes that cause breast cancer. And this is the photo I took when she came in 2023 to the FACU. So well, this with DNA repair, right? Let's leave it here. What is missing from classification mutations, if you want it later I record it or we watch it another time, so no It takes so long, but nothing, the idea was that we see generalities, the genome, Yeah? Important class to have today take into account everything about sequences repetitive from the beginning and after DNA repair mechanism here, right? How genetic changes can be repaired and if you look at the mutations, well, Let's go to the second part, eh guys mutations that exist. Yes, so nothing, Up to here everything was understood then good. Yes, great. Good, spectacular. Well, We'll see the other one later, so the brain we are talking about it. They are I record. Yeah. Come on, you guys for coming. Bye, bye, us we see. M.