 Thank you, Mark. All right, good afternoon. I'm excited to be here with this very questioning audience. That's a good thing. I will... I'm focusing today on one segment of the genome, the chromosomes 1 to 22, and so I've circled the genomics down here on the bottom left. But I do love the word integrating, and I wish we could be doing more and more of that. We do our best without what we have. Okay, so moving forward to... Let's see. So our genome resides in our cells. Our genome resides in our cells, but it's scattered around a little bit. And so in this slide here, I have a bunch of the orange wiggly lines, and if you've been to the genome exhibit, you might have seen other representations of these things we call chromosomes. And there's a brighter red one and a lighter yellowish one. The brighter red one is indicating it's a slightly shorter chromosome, the y chromosome, and the one next to that, the larger lighter colored one is the x chromosome. We also have DNA out in these other organelles called mitochondria, little rings of DNA that we inherit from our mothers. And so this is, you know, all together makes up our genome, and so I want to show, you know, where our ancestry is in terms of those different parts of our genome. So I don't think I can point very well here. What we have here is a little family tree, and I'll just show you the family tree. We've got two individuals, a brother and a sister, and what I have imagined when I put this little diagram together is that they, each of them has, they have two parents and the left hand, the boxes are always the males, the circles are the females, so you've got a father and a mother, and then you've got four grandparents and eight great-grandparents. And I'm imagining that the top generation there came from four different continental regions, the father's, father's parents came, let's say, from the purple, the purple arrow, say, from Western Africa, the father's mother's family came from, let's say, Iberia, Southern Europe, the mother's father's family came from Southeast Asia, the mother's family came from, let's say, eastern South America, say, Brazil. And so let's imagine this is a wonderful family that's got ancestors from all these different regions, and how is that going to look when we map that ancestry onto the genome? And because of the way the different genomic regions are inherited, what happens is the Y chromosome, which is inherited only from father to son, I've colored here purple, reflecting that the Y chromosome is traveled from the great-grandfather to the far left, and those great-grandparents, we're hypothesizing, came from Western Africa. So now on the other hand, to the right, we have the mitochondrial genome, which comes, is inherited from mother to child. So we see that I've colored that with the blue color because it is inherited from the mother's mother's family, and that part of the whole family we've suggested immigrated from, let's say, Brazil. And then we look at the rest of the chromosomes. Chromosomes 1 to 22, these are called the autosomes, and those chromosomes are so valuable because they capture not just one of the lineages of ancestry, but they capture all of those great-grandparents or those geographic locations. And so I've color-coded, you'll see these other chromosomes, and they all have four colors because if you look at the four grandparents, they have four different colors, and each of those chromosomes gets some material from each of those grandparents, and that's an important concept. So this is how our ancestry travels through our genome and through our family trees and in different parts of our genome. And so one of the important things to do is to bring all of this information together when we're trying to use DNA to understand our ancestry, to look at the different parts of the genome and put it all together like a puzzle. So, and another tricky thing is I gave you a little diagram that showed the eight great-grandparents, but a generation back, you were up to 16 great-great-grandparents, 32 great-great-great, and 64 fourth-great-grandparents. So really the number of ancestors grows so rapidly that we're looking at a very complex situation when we really look at a full family tree. But I wanted to be a little bit concrete here and look at one person's family tree, and this is a friend of mine, I'll just call him Roy, that's not his full name, but Roy knows a lot about his family tree and he hasn't sketched out and he gave me this sketch of his family tree, and we see, we've got Roy down at the base of the family, his mother Estelle and his father was also called Roy, and then we've got some grandparents written in there, great-grandparents and great-great-grandparents, and so Roy knows the names of many of these individuals and where they lived, but he also has linked a kind of racial identity or ethnic identity with each of these individuals, including himself, and so that's what I put here, and Roy considers himself to be black or African-American, both of his parents to be African-American, and his mother's parents to be African-American, but his understanding is that his father's father was Jewish and his father's mother was African-American, and going back further in time, on his mother's side, he understood one of his great-great-grandparents to be white, another to be Cherokee, and going back to yet one more generation, he had a Creek ancestor, so he has a lot of information about the sort of the identities of these individuals. Of course, he wasn't able to ask all of them, he is attributing this, and we do that a lot, I think, we attribute characteristics to our ancestors, and he's done this for his family tree, and so when we look at the genetics, his genetic variation, we can examine it in light of his understanding of his family tree, and so what we're trying to do is actually paint Roy's chromosomes just like the ones down here are painted, depending on geographic origin, and so, but how do we do that? We're all really pretty similar to one another, and how do we really have the power to really paint chromosomes based on ancestry, geographic ancestry, when we're all very similar to one another? Well, that 0.5% difference is among us, is enough to really see some information, and I'll show you, so we summarize that the differences are measurements of the genetic differences in lots of different ways, including something called principal components analysis, we've seen a little bit of that already from Jake, there are ways we make family trees of not just individuals, but also of populations, there's some analyses called structure where you actually can analyze data for many individuals and pull out a geographic variation, and I will be focusing on local ancestry inference, where you really try to paint a chromosome with an individual's ancestry at that genetic location, and this is just a principal components analysis, and I call this a global pattern of genetic variation. If you take individuals from around the world, and you just ask this particular algorithm called principal components analysis, to spread them out in a way that sort of mimics the genetic differences, and this is what you will see, and this pattern comes up repeatedly that you take any global set of individuals and look at their genetic variation, this is kind of what you will get, kind of this triangle with individuals from Africa in the lower left, individuals from Europe and the Middle East in the upper left, and then Eastern Asian and Native American individuals, their DNA samples will fall out to the right-hand side there, and so it's very much a kind of mimics geography, and that is because geography has really formed patterns of human genetic variation, it's because of the migrations throughout the last tens of thousands of years that we see this pattern. People who live near each other are genetically more similar to one another, and that's true all over the world because they've had interactions. And if we go back 50,000 years or more, we can look at how we've really, the history of our species is one of people migrating to nearby territories, and starting somewhere in Africa we're not absolutely sure where, but migrating throughout Africa to different places within Africa, but then also outside, reaching all the way to Australia, reaching to different parts of Eastern Asia, getting into Europe somewhat recently by 35,000 or 40,000 years ago, and then by 15,000 to 18,000 years ago getting all the way into the Americas, all the way down to South America, and this is simply by moving people moving from one place to the next. And so over tens of thousands of years this is the overall migration pattern, and that's the pattern, that is the migration history that led to this pattern of genetic variation that we see today. But I want to note that much of what we're looking at is migrations that have happened in the last 500 years where people have been able to cross oceans either willingly or unwillingly. I came across an ocean about 40 years ago myself. But also I want to keep in mind that people are still moving all over the place. There's a lot of movement still. We're not static, and places are changing names, groups are changing names, individuals are changing names, so there's still a lot of action as people move around our planet for one reason or another. So we haven't finished migrating, so this is kind of an ongoing process. But we're mostly focusing on the last several hundred years when we're trying to infer ancestry from this pattern. So the main approach that we currently use to infer, to do this local ancestry inference is to slide along any given chromosome. So starting, so the numbers on the left indicate probabilities. A probability of one means that we're highly confident in something. So the colors are shown down below where we've used the red to indicate Western African ancestry. Blue is Northern European, the brown is Southern European, the green is Native American. And so starting at the left-hand side of the top bar, so that each of these bars is basically a chromosome, so we can say this is an individual's, maybe the mother's chromosome, chromosome one, and sliding along we see that the first part of the chromosome there's a high probability, given our algorithm and our reference data, that that segment of the chromosome traces back to Western Africa. And then we come to a region where the algorithm is a little confused. It isn't sure if it's Northern Europe or Southern Europe. And so it does not give a probability of one to either one. Then we come back to a region where the algorithm is very confident, probability one or close to one, that that segment traces back to Western Africa. Then we come to a region, the brown region, that looks like it really is strong evidence for tracing to Southern Europe. On the second chromosome below, there's strong evidence for Native American ancestry, then Western African, then Native American with the green, Western African Northern European, then more Western African. And so this is all done with a machine learning approach and where you basically assign probabilities to the ancestry. And the key thing is that we have to compare an individual's genetic information from those chromosomes to the same chromosomes of people from all the different regions around the world. And these are the regions and the reference samples. So I think what is already started coming out today in the discussions earlier is that the reference populations that are used for any genetic ancestry inference are critical and the larger those populations and the more rich they are in terms of what geographic and cultural groups they represent are critical. And so this is the current state of affairs for our approach. And so we have three regions within Sub-Saharan Africa, a sample from Northern Africa and samples from these other regions and they number either in the hard run or in the thousands. So now what we do is we know people are interested in accuracy and how confident we are in the answer and the result. And so we choose a threshold and in this case it's a 70% threshold where we do not call something unless the algorithm is 70% confident in that answer. So here there would be confidence in the western African confidence in the Native American, confidence in the next segments of western African but then not much confidence in northern Europe because it doesn't go above the 70% confidence level. And so this allows us and someone who obtains this information to kind of get a sense of how confident we are in the result and a very critical point. All right, so let's see what happens when we actually apply this to somebody's data. Oh, and so we do a lot of testing of the algorithm and all of this is something we actually report and make available to the recipients. Okay, all right, let me quickly rush through here because to get to some actual information. So this we met Roy earlier and we see when we paint his chromosomes with the ancestry based on genetics, we see this mixture of red and blue bars, sub-Saharan African and European and the Jewish ancestry comes through very clearly with the genetic testing and we can actually add up the different pieces and this is how you get percent ancestry from different regions by adding up the lengths along the chromosomes and so he looks like he has about 50% ancestry tracing to sub-Saharan Africa, 43% to Europe, to different parts of Europe, different groups within Europe and actually we can even break it down to what he received inherited from his father and his mother and I don't know if you recall, I mentioned that his father's father was Jewish and this we can see here that his Roy's DNA himself shows that his father was half Jewish which is exactly what would be predicted by the family tree and so what we've done here is show how Roy's understanding of his ethnic ancestry is really recapitulated by his genetic analysis and so this is at least one case where we can see how does the genetic result hold up compared to paper records and other kinds of information as we try to integrate all of this. All right, okay, this is the most common question we get from customers or one of those most common ones is can a DNA test prove I have Indian ancestry, Native American ancestry and this is very challenging so it's not something that we say necessarily will prove but it can give hints of Native American ancestry so now I want to say something, right now we have over 400,000 customers people have signed up for 23 Me's service and this is some indication of their backgrounds I was getting that we have over 10,000 African American customers many of them have told us their place of birth and they come from different regions in the US so when we look across 1,600 individuals who actually have self-reported that they consider themselves identify as black or African American so when we look at their ancestry and break it down into different regions we see most of them have mostly the red which is Sub-Saharan African the green is European so most of them have some European some have quite a lot of European ancestry but it really, really varies as we heard from Jake just previously it really varies from across all the African American individuals all right, couple things the average African ancestry is about 70% and when we break it down we also do some, you might be happy to see that ancestry.com and our current state of affairs are very similar we have very broad regions such as western Africa, eastern and southern Africa so we don't really break it down that far and we're working on how to do that okay, all right, so I better just do one more so, yeah so exact same statement that Jake made nobody's going to be surprised about that but if it came out differently you might question us, right? you might wonder all right, so European ancestry of African Americans mostly goes to northern Europe a little bit goes to southern Europe some to eastern Europe and some African Americans shows a small amount of Ashkenazi ancestry all right, okay so I think we'll stop there and let the next speaker get started thank you that's really great Joanna, sorry to have to interrupt that lots of great information and I know there's a bunch on the website too you guys have demo accounts and other information maybe there's other sources you can mention during the panel part but it's my pleasure now to introduce Dr. Rick Kittles who's a professor, been working in this area a long time and won't bother delaying his start