 So good afternoon. I think we should go ahead and start. It's a little over two o'clock. I want to thank the people who are here in person and also people who are watching us virtually. And you can send in your questions. We are monitoring the virtual questions and for the people in the audience, please use the mic after our wonderful speaker is done with his talk. So it's my pleasure today to introduce Dr. Eduardo Tarrazo Santos. I hope I didn't kill that. Who was this morning I learned that he was born in Peru and doing most of his work now in Brazil. He has a doctorate in both biochemistry and anthropology. And during his postdoctoral training, he worked with Dr. Sarah Tishkov, which most of you who are track population genetics is one of the big time population geneticists at the University of Maryland. And Dr. Steven Shannon at NCI. He is a professor of human genetics at the Federal University of Minas Geras. Again, you can say that when you come on stage so people actually get your eyes pronunciation in Brazil, one of the leading academic institutions in Latin America. He's an expert in population genetics and the chief of the laboratory of human genetic diversity are focusing on understanding the genetic diversity and genetic basis of complex traits and diseases in indigenous and admix populations are from Latin America. He is the leader of genomic and bioinformatics analysis in the epigen of Brazil, the largest Latin America initiative in population genetics and genetic epidemiology, which has genotype and sequenced approximately 7000 Brazilians. He's also the leader of the LC Brazil, the longitudinal study of aging, including the Brazilian representative sample of those to 10,000 individuals. He's an active participant in international network, such as the Ibero American network of pharmacogenetics. He has mentored more than 43 needs in population genetics and bioinformatics. On a personal note, one of his mentees, mentee as we've actually with a quiver, let me just put it that way. He's now a research fellow in my lab with our standards case in population genetics and genetic epidemiology that led to a successful K9 application. Eduardo, we thank you for all you do to increase diversity in genomic science. Please join me in welcoming him to give us a fantastic talk about genetics and genomics in South America. Thank you. Thanks. Thank you very much, Charles for the presentation. For introducing me. I am very honored to be here. I am very honored of giving this direct NHGRI director seminar, and I thanks Charles and Matheus for inviting me for this talk. I am very happy also to be here again in the NIH where, as Dr. Otimi say, I have been a postdoc several years ago. Okay, we will talk about the genomics and population genetics of both Native American and then mixed populations of Latin America. This is the topic of our research group in Brazil. And so we will talk about ancestry and disease in Latin America and genetics population of Latin American groups. In this closure slide, I don't have conflict of interest to disclose, and we will start to talk in general something about ancestry I know ancestry is a very, very complex and sometimes difficult concept to understand, but for we that Native American or that work on Hispanics is very useful. It's very operational to be able to think in terms of continental or subcontinental ancestry and we will when we talk about that, we have several terms we can talk about individual ancestry, which means that we can define the proportions of, in our case, African Native American or European ancestry for each of us. We can talk about population ancestry when we talk about a specific group of specific populations, but no we can see some years ago we are able with enough data to infer ancestry of each piece of chromosome of each piece of our chromosomes. This that it seems to be an exaggerated thing and exaggerated concepts we will see is very, very helpful. One point important is this there is a lot of discussion about what ancestry means. We think in terms of our history in Latin America is very relevant to think about continental ancestry. And this is because in terms of population genetics or also in terms of health. The fact that Europeans and Africans started to arrive to our continent 500 years ago was a very, a very important event in our history, and it's an event that have determined very important components of our health, but also of our social history. So, I think, considering the African European and Native American proportion of our ancestry is very, very helpful, even if you also can think about which part of your genome, for example, comes from Neanderthal or Neanderthal. But I think in terms of our social history is not as much important as to think about what happened after the arrival of European Africans and how they interacted with Native American in our continent. I will talk about, I will divide my presentation in two components. One is the, I will talk before there are four three concepts that we will talk about. One is ancestry, I said, then we will talk about Native American population genetics, how the environment, the genetic structure, and how environment and genetic structure influence clinically actionable pharmacologists in Native Americans. And then we will talk about at mixed populations in particular in Brazil. So, let me find concepts in my presentation that I think are very, very, very important in our research in South America, in Latin America. One is, and I will show examples of this and I am very happy to say that I am at the NHGRI in a place where you actually do a very, you have very, very, very big fair north-south international collaborations. And the other concept is that this international and fair international collaborations has to be connected with training of human resources of young investigators also in Latin America. This is something we do every day. And I think these two components are very, very important in any global initiative of genomics. Let's talk about how environment, how the history have influenced the genetic structure of some Native American populations. You are, you have in this cartoon pictures, pictures of some Peruvian Native Americans. We are studying as together with Peruvian institution of the National Institute of Health from Peru, the genetics of Native American groups in Peru. You can see there two very, very important biomas in Latin America, which are the Andean mountains, which is a high altitude environment. This environment, this region that you see there is geographically, this is equivalent in terms of area to the Iberian Peninsula plus French plus Austria together. So this is a big area. And there are two very, very important environments there. One is the Andean Mountains, which is associated to a high altitude and to hypoxic environment. This is very dry environment. There are, and you have at the east of these mountains, the Amazon region, which is also a very, very relevant environment in South America. Okay, there are millions of people living in this environment. We studied the genomics of these people together with the Peruvian National Institute of Health and together with the University of Maryland, Tim O'Connor from the University of Maryland, here in Baltimore. We have a very, very good experience doing this project. We studied something like 18 populations on more than 200 individuals. And one of our findings was this, okay, how is structured the genomics, the genomic diversity of these populations and took it with local archaeologists and people from Peru. It came out that we have two regions in Peru, a region that is called the fertile Andean region, which is at the north in Peru, and latitudinally a southern region, which is normally called the arid Andean, which are more arid, but also are higher in terms of altitude. Okay. And the interesting thing is that this environmental division recapitulated in a certain way the genomic structure of this population recapitulated these environmental differentiations between fertile Andean region in the north and arid Andean regions in the south. What you can see is this, okay, in the northern part of the Andeans, where Andeans are lower, there has been more gene flows between populations, and so the different populations living in the Andean area and the Amazonian area share a pattern of admixture, we can see here green components of admixture, which correspond to the ancestry cluster, shared by people living in the Andes in the coast and in the Amazonian region. But when you go to the south of the Andean region, and you have higher Andean altitude, you can see that the genetic structure of these populations is very, very differentiated. We almost don't see here green components of ancestry, and in these populations who are living in the adjacent Amazonian region, you don't see an ancestry component which is typical of the Andean populations. So you have a north-south pattern of diversity, and in the southern and arid part and higher part of the Andean region, we have a very differentiated genetic structure between the Andes and the Amazonian populations. So these have determined, for example, several interesting things. For example, the action of natural selections that have acted differentially in the Andean populations and in the Amazon populations. So we have found very, very interesting signatures of selection. Okay, here, we found different evidence of natural selection and positive natural selection, adaptive natural selection, acting on genes, on particular genes in the Andean region. And in the Amazon region, we have found very different signals of natural selections in genes like CD45 and TPR-SS6, which is part of the hematological and iron metabolism function. In the case of CD45, this is a very important molecule in host and in the Amazon region, we have found very different signals of natural selection in genes like CD45 and TPR-SS6, which is part of the hematological and iron metabolism function. In the case of CD45, this is a very important molecule in host-viral interaction. Okay, so, but in addition to this, we published it a few years ago. This was a paper we published in 2020, more or less two years ago, published by Victor Borda, who is who was my PhD students from Peru, and now he's in the University of Maryland. But then we were interested in looking for the distribution of clinically actionable variants in terms of pharmacogenetics. We found two very, very interesting results that exemplifies how these projects about genomic diversity may be particularly important to find clinically relevant information. One example is this gene, which is this variant, which is involved, which is related with the Rosovastatin pharmacogenetics. This is a clinically actionable genotype. And this is particularly relevant because you can see that this variant is, there is too much attention on the differentiation of this variant in Asian populations. So there are different regulatory agencies that make recommendations regarding that is Asian populations that have a frequency of around 30% of a little T should start the treatment with a lower dosage to avoid side effects. When we observed a compare and the populations with Amazonian populations, we figured out that the differences between and Amazonian population are as larger as the difference between Asians and not Asian populations. So the size of the differences and frequencies were as larger are the more prominent diverse diversification that this well known and this observer in East Asian population. So even in a in a region like Peru, we can observe in native population, big differences between in different geographic regions. Another very important example. This is a variant that is very important in barfaring treatment. So in many populations there are recommendations to genotype these variants to and to include this information in algorithms for those such of warfaring. This is very relevant in low-medium income countries. Why? Because in high income countries we can, you can substitute warfaring by other drugs, but these drugs are among 10 times or 20 times more expensive that warfaring. In low-medium income countries, this is not possible. So probably for many years warfaring will be the drug to be used in the case of thrombosis and it will be important to perform pharmacogenetics testing of few SNPs, one, two SNPs to adjust the dosage of warfaring. In this case, again, we are observing between Andean populations and Amazonian populations, differences that are as higher as those observer between that are well known in continental groups like East Asian respect to North East Asian populations. So these are two examples of how, and there is an additional problem in the Andean regions, is that we don't know, there is no an algorithm for dosage of warfaring in the Andean regions, which would be important to develop because there is a problem of high altitude and the altitude can influence the metabolism of warfaring because the adaptation of Andean populations to high altitude is mainly based on cardiovascular mechanics. Okay, so these two examples show three things that of course, and maybe obviously genomic studies in neglected populations may reveal clinically relevant information. These examples show the inadequacy of ignoring the internal genetic structure of ethnic groups, such as Native American and these findings put challenge to concepts such as Russia pharmacogenetics, or that maybe considers the groups the continental groups as homogenous. And this problem also shows how environment environmental stresses on the cardiovascular system such hypoxia in the Andes posted new challenge for the understanding of the effect of genetic variation on drug response. Okay. So, I wanted to show these two regarding Native American populations. And now I would like to show our work on at mixed populations. These are my collaborators in the project of the Peruvian genome project. This is from the Peruvian National Institute of Health, Robert Gilman from Cayetano ready and Hopkins and Tim O'Connor from the University of Maryland in Baltimore, and we are doing these and other stuffs in the context of the ever American network of pharmacogenetics together with a very good Spanish collaborators who is Adrián Llarena. So this is about Native American populations, but in addition to indigenous populations in South America. I know we are in the month of Native American heritage. We have also at mixed populations in in different across Latin America as you have here, the US Hispanic people who are the descendants of Latin American people. Okay, we have been working on a while for with at mixture and disease in Brazilian populations. We were working for several years in the project of AP Gen Brazil. This was a very big initiative of the Brazilian Ministry of Health in particular of the Department of Science and Technology of the Brazilian Ministry of Health. The Brazilian Ministry of Health funded the genotyping around 6000 individuals and at that time that was a larger genomic initiative in Latin America. This is part of a network that involved people from several institutions on Brazil. And now we are moving to the genomics of the Brazilian aging longitudinal longitudinal study. Okay, I want to show you some results regarding these projects and the work of our groups during the last few years. These were the three population based Brazilian cohorts that were genotyped and some individuals were working on sequencing one Brazilian cohort from North Eastern Brazil which is very, very, which is more African than the other cohorts, one cohort of age and aging cohort in South East Brazil and one cohort in the south of Brazil. These are the three most populated Brazilian regions. We were focused particularly in the African parts of the of the Brazilian genomes and we were focused on that because we know African and Native American are our parts of our genome that were of African or Native American or were our have not as much there is not as much research on those region on those genomic regions, respect to European information from the European part of our genomes. So we have some questions regarding the population genetics of these groups. For example, we were looking at in a we were looking at in a in a project that was led by my materials. Okay. If there was a correspondence between the geographic origin, a specific African population of the diaspora and a specific destination in the Americas, we created a data set with different populations in Latin America and also African American populations. And we look at for subcontinental ancestry in a different African and Latin American populations. And as we already know the West Central African associated cluster is the most relevant is the most prevalent in most African American continent populations. And we saw also that there is a Western Africa ancestry, which is not almost not present is absent almost absent in south of South America. The Western Africa associated cluster is more prevalent in northern latitudes of the America, and here has a very low prevalence in Southern South America. Then we have a component of Southeast Africa which is associated with back to population that shows the highest proportion in how in South and South Easter Brazil. And we were interested in trying to figure out which are the historical and the geographical factors that influence this structure of African diversity in the Americas. One factor was latitudinal proximity probably. Okay, another factor where the ocean currents and winds of that divided that created two systems of navigation in North and South Atlantic. And it was related also probably with geopolitical factors, because the control of North Atlantic route was in the hands of British people who abolishes slavery in 18 seventh. And because on the other side Portugal influence in Angola, Mozambique and Tanzania and Portugal, Portugal ships ships brought people to the South America to the Brazil in particular, and because the Portuguese uses Southern Atlantic roads to bring slaves to Brazil in particular to Rio de Janeiro. Okay, so our first conclusion about this question was that both geography and geopolitics influence the geography and linguistic diversity of Africa African migrants as well as favorite the regional differentiation of African ancestry in the Americans. Okay, then we have another question. Our second question was this, considering the geographic extension and the massive demographic manage magnitude of the African diaspora, and the level of population differentiation between populations in different African regions. The transatlantic slave trade led to a very similar level of structure of between population differentiation in in the Americas. So we are looking only to the African portion of Latin American genomes. Okay, and what was the answer to this we were worried about this, because you can see here that African African cluster of the genomes, you hear him in blue in yellow, or in purple are more structured and more geographically differentiated that in the Americas, in the Americas, they looks more homogeneous. When we did a formal test for for this, we saw you can see here that the FST which is a measurement of between population differentiation is lower in the African diaspora distribution for SNPs in the America was lower than in Africans. What does it means. This means that the African diaspora after the African diaspora will serve an homogenization of the between population of genetic variation associated with the African diaspora, which is was probably the product of a mixture between individuals in the in the Americas. There were some historical facts that might have contributed to this. So despite their specific European origins trade those vessels to transport their slaves frequently illegally to different American ports. There was also a process called forced amalgamation, which is the preference we was the preference of the slave owners for slaves from different geographic and linguistic origins. And to avoid that each, they understand each other. And it was also very important the role of the island such as Jamaica and Barbados that centralized parts of our evil of America of African people, and then redistributed these people in different parts of the of the of the continent. So the population genetics is able to trace the African roots of a mix and individuals of the Americans to a broad geographic extension that goes from Western Africa to East Africa, associated with a high linguistic diversity from Niger, from Cordofanian regions to Western and Easter band to regions and historical facts homogenized the between population components of genetic diversity. And these forces have predominated over that evolutionary forces that have differentiated the genetic diversity of our African portion of our genomes. We were talking about that mixture mapping which is a technique that allow us to use that mixture to find variants that me may be responsible that may influence complex trade. In this case, BMI or obesity. Okay, so we were with the value we perform it and make sure mapping a looking for European associated or Native American associated fragments of the genome that may be associated with a BMI or obesity in Brazilian in our Brazilian cohorts. We had three Brazilian cohorts three at mixed Brazilian cohorts with different distributions of BMI. We didn't put all the individuals together because the age distribution was was very, very different. And so this is what we found. Okay, when we specifically studied, we found an association. For women, this is very, very important. So we found a for women from southern Brazil from pelotas cohort in Brazil, we have, we will find a specific region of chromosome 13 that were more likely African in obese women. So this means that that region in chromosome 13 should contain a genetic variant of African origin that predisposed to obesity. This was very, very important because this cohort, these women had only 15% of African ancestry. This means that even if you study in Latin America, a white population. Okay, it's very, very likely that these white people that self classify as white, for sure we'll have a fragments of their genome that have African origin. And in particular in south of Brazil, they can have African segments that may come from, for example, regions from South Africa that are more common in southern Brazil respect to the Caribbean or the North America. Okay, so the first thing that we have was an association with a negative association for chromosome 13 with European European pieces of DNA. When we look at that, it came out that these pieces were predominantly Africans because these populations were mostly a mix of Europeans and Africans. This only happened in women. Okay, when we perform a fine mapping, we look at, we identified a specific variant, which is this one in this region that was associated with obesity, which was strongly associated with obesity with BMI in mixed women of southern Brazil. Okay, but then we said, okay, but this is too much, this is too strong association is four units of BMI for each allele, and we didn't believe in that. And there was a problem because we, this was an imputed variant. So, even if we observe it as strong association, we were not so convinced. So we tested the association only in adult women from BMI from a different cohort, and we replicated the association. Okay, but okay, but this was, again, an imputed variant. So we look at for a wall sequence data, wall genome sequence data for actually for a genotype data, because this may have been an artifact of imputation. And we, when we studied the association in a third cohort in Sao Paulo, we replicated the association even with a smaller effect. Okay, so we were able to find a variant that was of African origins in white people in a mixed women. Okay, that is associated with obesity. And we try to replicate that finding in different in different populations in Puerto Rico we didn't find association in Africa, we didn't observe that association with with that. We did that with people working with the H3 initiative. We collaborated also with Saradishkov, we didn't observe that association. So this seems to be a variant, which is, which has an African origin, but seems to have an effect specifically in women and specifically in mixed women. Okay, and we replicated that we replicated that finding in three Brazilian cohorts, one of them, including world genome sequencing data. So when we performed a meta analysis, we found that the association was a was present. Okay, not in all the populations we allow it for heterogeneity, but we observe but that this variant seems to contribute to an average of one unit of BMI for each, which even is not our original finding of three units of BMI. So these are very relevant variances to be a very, very relevant variance. When do you think when we think about the effects of variants that are contributing to obesity. This is an example of variants of how at mixed populations may be used to find variants of African or Native American origins that contribute to complex disease studying Latin American at mixed populations are using a family of association studies such as admixture mapping or other techniques that are currently using like the tractor or even considering local ancestry as a covariates and consider including the concept of local chromosome. Okay, we published this in one year ago. And finally, okay, we were, we are particularly interested in terms of population genetics in not only to take pictures, present pictures of that mixture, but also in a inferring the dynamics of the process in the Americas. Okay, so the current methods the most recent methods in population genetics tried not only to to to have a picture, very high resolution pictures of admixture, but we want to be able to tell how this process occurred a long time. So we were using a concept who was the fact that when you had to make sure the tracks which are pieces of chromosomes from different origin, when you had a mixture populations tend to have more tracks more fragments of different and these fragments tend to be shorter and shorter and shorter, more admixture you have this process, and we are developing this this idea, we are capitalizing on this idea to develop a method basic on ABC approximate variation computation to infer the dynamics of the process of admission what does it means it means to be able to infer the contribution of African European and Native American, a long time for example for each century, or even a continuous function of admission along the last five centuries for example, what was what when we use this concept of increasing numbers and smaller numbers of chromosome segments of different ancestry, and we apply this method in 2015 to Brazilian populations, we found a very very interesting results. Okay, focus it on Native Americans. When would you look at the sizes distribution of pieces in Brazil of Native American ancestry, you see these pieces of Native American origins are relatively small are very small. Okay, and when you estimate with you with our method, the contribution, a long time, you see this 500 years ago, the contribution of Native Americans, the Native American contribution war where about in different Brazilian populations, more than 20%. Okay, after that, the contribution decreases sharply. And why this happened, this happened because the Native Americans of Brazil were actually decimated. Okay, the small Native American contribution was concentrated in the first pulse of admission immediately after the arrival of European, and this is the genomic signature of a population decimation in Brazil. Okay, so genomics can be also used. And this is very important in today where sometimes genomics are are are used or might be used wrongly to justify. In some instance, there is a very interesting papers in nature. A few weeks ago, racist behaviors genomics can be also used to infer our history to infer social aspects of our history. In our case, for example, Brazilian who have very low level of Native American at the picture have the signature in their genomes of the process of decimation of Native American populations. We are interested in particularly in a process that is called the dynamics of sexual ancestry bias. It means that in Latin American you frequently say that in this is related with our social history with the process of power of European with the use of power of Europeans, African Native Americans. And for the reason is well known that a, when you look at the mixture in autosomal chromosome and the X chromosome frequently the European at mixture are higher in the autosomal and the African and Native American at mixture is more is higher in the X chromosome. Admixture has been mediated, African European at mixture have been mediated by males predominantly and African and Native American at nature have been mediated by women predominantly. Okay, there was a correlation this is what what is called a sexual ancestry by bias technically. There are developing methods to infer the dynamics of this process not only to infer the dynamics of a mixture, but only to infer the dynamics of these sex ancestry bias. Okay, these are some results for example, for Salvador for Salvador we have, which is the most African portion of Brazil. We have evidence in our genomes of a preferential a mixture between female Native Americans and males Africans. Okay, and we will look for the dynamics of that process. Okay, we look that after the 16th century, we have an increase in the, in the, in the, in the marriage between European males and African females. We have the process was stabilized, stabilized, and then it increased again in the 1920s centuries. Okay, so we are developing methods to infer this this kind of process which are part of our social history, and our history of relationship of power between African Europeans and Native Americans. And this is one of the reasons, because I think for us in Latin America, when we talk about ancestry to talk about European African Native American ancestry is much more important that considering ancestry just as such an abstract concept, because most of our history has been dominated by the interaction between African Europeans and Native Americans. So, I just wanted to show you some of our work how a population genetics as ancestry concepts may have we have we have used these concepts, not only to find a genetic variance that influence a complex trait like BMI or obesity, but also to infer how important aspects of our social history, and how the environmental diversity in the case of Native Americans of the Indian Amazonian region can contribute to influence the distribution, even of clinically relevant variants like we saw in the examples of the Bacetean pharmacolils and warfarin pharmacolils. I want to thanks my research group. Mateos was part of that and was part of part of these analysis I show I want to thanks our Brazilian fundings agencies, in particularly the program genomes Brazil from genomes Brazil from the Brazilian Ministry of Health. And thank you very much for our presence and I would like to be able to answer your question is you have them. Thanks. Okay, while we're waiting for while we're waiting for some of the live ones we can do some of the online questions this first one I think came in during your discussion of BMI. And it's asking what was the signal on chromosome 20. I don't remember. Yeah, the paper there are other signals that some of them are reproduced we reproduced several of the other signals well know to be associated with with BMI. Other signals. I don't remember exactly the, the, the signal on chromosome 20. Okay, but if the, the person who asked email me, I can send the information. I learned a lot of history just listening to your talk. That was quite revealing. You can hear me. Oh, it was me. Okay, I thought I have a loud mouth so I use. But anyway, I just, I was just curious that all through your talk. You didn't say anything about Asian admixture or ancestry in Brazil, and I was just curious, is there any documentation of that. You spoke about Native American, African and European, but nothing about Asian I was just curious where that as part of the history. Yeah, we found in our cohorts, we had only one individual with was 50% Asian and 50% European. So because we had only that signal. And we didn't have evidence of, at least in the Brazilian cohorts we were studying. We didn't focus on that but of course, that's the Asian contribution is relevant. For example, probably, Sao Paulo is one of the largest Japanese city in the world. Okay. For example, in Peru, we also have a very, very relevant Chinese community, we have a China town in Lima also for example. And, but we didn't, but because we didn't have a signature of Asian of an Asian component in our cohorts, we decided not to include them in the in the but that would be terrific to figure out, not only the but when we will work at more a higher solution of Chinese immigration in in in Western South America, or Japanese immigration in Brazil but also for example Middle Eastern contribution to different parts of Latin America, both you with population are also Arab components that may be present in different parts of the continent. Okay, thanks. Thanks for that fantastic talk. This is Deborah demo from energy era. Two part question. The first one is, how good are the reference invitation panels like 1000 genomes and top med for the Brazilian populations that you study when you do invitation for G was studies. The second part is more related to that which is, are you planning to do whole genome sequencing. In case there are variants that are not currently known that you may discover in these populations. Thank you. Which we developed it and and we recently were testing a Brazilian imputation panel that included a Brazilian horror 1000 individuals called Sabi, that was sequenced by a Sao Paulo group from Professor Maya Nassat and Michelle Naflaski. So we were testing the imputation with that we are assessing how good is the imputation with the top med panel and the Brazilian plus 1000 genome panel. And in particularly, if we can do something like meta imputation, which is a concept I learned in the SAG meeting last last week, or maybe to put together the Sao Paulo cohort which is all across Brazil from Michelle Naflaski and Maya Nassat groups with other with other panels. Okay, so we are working. Actually, we have a very good imputation pipelines in our group. And so we are working with them to do the testing to figure out how is the best way to do imputation for Brazilian data. There are some world genome sequences initiatives in Brazil. When we work on that in 2012 13 we only sequenced 13 individuals, then a, the larger set of Brazilian individuals that's having sequencing have been published with our imputation in the analysis last year, this is this are one around 1200 individuals from a court called Sabi. We have been very, very happy of be part of this this is from Michelle Naflaski and Maya Nassat group. And then that should be coming out new data. There are something like 23,000 Brazilian that are being sequenced by a very good Brazilian population, scientists like Ligia Pereira and Alessandro Pereira and Tabitha Hunemair. They should publish in some months. And there is a very interesting initiative of the Brazilian Ministry of Health to do world genome sequences of Brazilian cohorts. And so we hope to be able to sequences for example, the ELC or the APJ cohorts to generate NGS data for for for them. Some more online questions anonymous one are the Europeans that colonized Brazil of Jewish ancestry. Sorry. Are the Europeans that colonized Brazil of Jewish ancestry, or is there a significant. I know there is a publication we didn't we didn't work on that but there is a publication a few years ago from the andrew recently notice group that show it the very interesting thing that was that people that the Iberian country in Brazil, okay, came from people that at that time at the time of the of the of the colonization saw something like five centuries ago, they were called new Christians in the Iberian Peninsula, and these were probably converted to the to the Christian religion, because it was better to be a great Christian in the Iberian Peninsula, and then migrated to the to the to the Americas. And andrew renadies groups few years ago found the signature of this, the genomic signature of this migration of people with the Jews origin convert with were called it converses to to the Americas. I'm fascinated by the history of Brazil and South America in general. I was just curious, you've shown some very interesting historic things that genomics is revealing. I wonder, how do you, how do you interpret this for the general population to appreciate. I'm just curious, like when I was in Brazil, you can fit the whole skin color you see in the world, you can see it in the streets of Rio. So I'm just curious how is this social communication of your genomic findings. We have some activities for spread this this this knowledge we have some activities in the social network in, in, in, we were thinking about that so I think there are two levels of knowledge, one is the implication of this knowledge in health. Okay, so it's, it's very important, for example, to communicate that this kind of studies like we showed in the case of Native American can produce relevant knowledge but maybe very helpful, for example, to inform a code genetics there are very good examples. One is the, the Rosa was the thing example one is the bar bar firing example. Okay, and maybe to show that even in to show the idea I didn't show a slide that I have that even Native American. So, besides the admixture between European, but even if we consider Native American, they are a very diverse group, this is a very important concept, because there is an afforens by Antonio do your who was a traveler, a Spaniard traveling of 17, I think, who wrote a very famous statement, which if you so one American Indian, you have so all the American Indian something like this. Okay, and I think people for maybe now is more aware, for example, about the African diversity that this is very very good because African is a very diverse country. And even if you but I am not sure this is also true in the case of Native Americans. Okay, and this is even important, even more important for United States European investigators. It's important because, for example, when you when you think about Alex Hurd-Leaka Alex Hurd-Leaka was a very prominent check American, one of the fathers of American anthropology and one of the fathers of Native American anthropology native Alex Hurd-Leaka is a father of biological anthropology and have a statement at the beginning of the last century so in the 20th century. Okay, that were very, very similar to Antonio do your statements about the fact that all Native Americans are are very, very similar. Okay, so I did say this. I think this is a very, very important message to transmit. Okay, that's not all Native Americans are even genetically, of course, there is there is a big diversity between Native Americans. This is very important because sometimes, obviously that's that's better than nothing but we do big projects, divide in the people in Native American components Native Americans, the Peruvians from Lima are the representative of American people in the indigenous and genome project. Okay, but we need to be aware that that's not enough. Okay, and that was a lot of diversity related with environment with culture, etc. The other thing I think is that this is a very important concept in Brazil, for example, and this is, I am Peruvian, okay, and Peruvian is in Peru and Mexico archaeology is very, very important for our identity. So, because we have big cultures, very important cultures before the European arrival. Brazil, history, historical knowledge, derived from human population genetics about the history of Brazilian and mixture is as much important as is archaeology, for example, in Peru or in Mexico, this is something a person Ricardo Ventura from the Rio de Janeiro National Museum told me he has worked a lot on the history of Brazil. He has worked a lot on the history of Brazilian genetics. And this is so this studies are also very, very important to learn about our history, our social history, and our social history of racism in Latin America, because population genetics, how can show us a very important parts of our of the African part of the Brazilian history of the Native American part of the Brazilian history. This is one something we stress it because, for example, when Brazil, this is something which is called in Brazil, the Aurea rule, it was when the slavery was abolished in Brazil, they burned out all the registers about slaves. Okay, and was this means that part of Brazilian history has been lost. Okay, and I think population genetics can, in some instance, contribute to learn about our history in Latin America. This is also a very important component of our research. In addition, of course, to contributing to to to help which is something we're particularly interested and is our primary primary interest. So the questions keep rolling in unfortunately I don't think we can get to all of them because there's a still eight of them here, but maybe one more and then we'll we'll say sorry to everyone else. So from Elizabeth Atkinson very cool work I was very interested in your association finding in the African tracks of ad mixed Latin American populations that was not seen in populations from the African content. Was this due to a higher math in the ad mix populations if so do you think this is because of drift or selection. We don't know. Okay, we we that that's very, very interesting point we try it to we publish it all the results of our application attempts. So those that gave positive association and those that that did not. So, for example, we didn't see association in two African cohorts, one was the H3 African data from South Africa. And also in this was urban environment, I think it was Johannes Borgo or, and there was also data from rural areas from Saratischkoff group and we didn't see any sort, even, even not. We didn't see any signal. So, but we are very, very, we were very interested that we were able to do to to replicating three different Brazilian cohorts, okay, and Brazilian is a big country so it wasn't the same population. So it is also intriguing for us. Yeah, I think we have to call it quits but maybe one more round of applause. Thank you for Dr. Thank you very much.