Largest ever human family tree: 27 million ancestors

Researchers from the University of Oxford's Big Data Institute have taken a major step towards mapping the entirety of genetic relationships among humans: a single genealogy that traces the ancestry of all of us. The study has been published today in Science.

The past two decades have seen extraordinary advancements in human genetic research, generating genomic data for hundreds of thousands of individuals, including from thousands of prehistoric people. This raises the exciting possibility of tracing the origins of human genetic diversity to produce a complete map of how individuals across the world are related to each other.

Until now, the main challenges to this vision were working out a way to combine genome sequences from many different databases and developing algorithms to handle data of this size. However, a new method published today by researchers from the University of Oxford's Big Data Institute can easily combine data from multiple sources and scale to accommodate millions of genome sequences.

Dr Yan Wong, an evolutionary geneticist at the Big Data Institute, and one of the principal authors, explained: "We have basically built a huge family tree, a genealogy for all of humanity that models as exactly as we can the history that generated all the genetic variation we find in humans today. This genealogy allows us to see how every person's genetic sequence relates to every other, along all the points of the genome."

Since individual genomic regions are only inherited from one parent, either the mother or the father, the ancestry of each point on the genome can be thought of as a tree. The set of trees, known as a "tree sequence" or "ancestral recombination graph," links genetic regions back through time to ancestors where the genetic variation first appeared.

Lead author Dr Anthony Wilder Wohns, who undertook the research as part of his PhD at the Big Data Institute and is now a postdoctoral researcher at the Broad Institute of MIT and Harvard, said: "Essentially, we are reconstructing the genomes of our ancestors and using them to form a vast network of relationships. We can then estimate when and where these ancestors lived. The power of our approach is that it makes very few assumptions about the underlying data and can also include both modern and ancient DNA samples."

The study integrated data on modern and ancient human genomes from eight different databases and included a total of 3,609 individual genome sequences from 215 populations. The ancient genomes included samples found across the world with ages ranging from 1,000s to over 100,000 years. The algorithms predicted where common ancestors must be present in the evolutionary trees to explain the patterns of genetic variation. The resulting network contained almost 27 million ancestors.

After adding location data on these sample genomes, the authors used the network to estimate where the predicted common ancestors had lived. The results successfully recaptured key events in human evolutionary history, including the migration out of Africa.

Although the genealogical map is already an extremely rich resource, the research team plans to make it even more comprehensive by continuing to incorporate genetic data as it becomes available. Because tree sequences store data in a highly efficient way, the dataset could easily accommodate millions of additional genomes.

Dr Wong said: "This study is laying the groundwork for the next generation of DNA sequencing. As the quality of genome sequences from modern and ancient DNA samples improves, the trees will become even more accurate and we will eventually be able to generate a single, unified map that explains the descent of all the human genetic variation we see today."

Read more at Science Daily

The impacts from using genetic testing to track down relatives

Genetic genealogy has become a popular hobby over the past several years, thanks to direct-to-consumer (DTC) genetic testing and relative-finder services offered by some DTC genetic testing companies. In a paper published February 24 in the American Journal of Human Genetics, researchers report results from a survey that asked people who had participated in these services what effect the discovery of previously unknown relatives had on their lives.

Among the most important findings were that identifying a genetic relative appeared to be somewhat common. Additionally, those discoveries were generally experienced as neutral or positive and didn't appear to have a big impact on participants' lives. However, some participants learned things that could be considered significant and destabilizing -- such as that their biological parent wasn't who they thought. These participants were especially vulnerable to negative outcomes.

"Everyone on our team is involved in studying the ethical, legal, and social implications of DTC genetic testing, and we've been paying attention to stories in the media about individuals who've made surprising family discoveries from these tests and relative-matching services," says lead author Christi Guerrini of the Center for Medical Ethics and Health Policy at Baylor College of Medicine. "We wanted to understand if these and other kinds of discoveries are common, how they're experienced by those making the discoveries, and what people are doing as a result."

The investigators sent the survey to about one million DTC genetic testing customers and genetic genealogy database participants; more than 26,000 responded. The final sample for analysis consisted of 23,196 completed or substantially completed surveys. Among the reasons that respondents said they chose to participate in this type of testing were to learn more about their family or build their family trees; to search for a biological parent, child, or other relative; or to investigate a suspicion that they might not be genetically related to family members.

"It seems that many -- perhaps most -- are just curious about their families and interested in building out their family trees, but it's clear that quite a lot of participants are looking for someone or hoping to confirm something in particular," Guerrini says. "It might be that they're adopted and looking for a biological parent, or that they've always felt out of place in their family and want to see if there's something to that feeling. Or they might be looking for information about a branch of their family tree that's unknown to them, or to confirm a family story that's been passed down over the years."

Most respondents (82%) reported that they learned the identity of at least one genetic relative. Among this subpopulation, 10% identified a biological grandparent, 10% identified a full or half- sibling, and 7% identified a biological father. The survey asked whether the participant had chosen to contact any of their newly identified relatives and, if so, the reasons for doing so. It also asked whether their discoveries resulted in any life changes, including changes in health-related behaviors.

Guerrini says that the high number of people overall who identified an unknown genetic relative was not unexpected, because many of those relatives could be very distant ones. But she acknowledges that the high number of participants who found close relatives could be skewed by the type of people who choose to undergo relative matching in the first place. "Unfortunately, we can't answer that question with our data, but I'm very interested in trying to do so in future research," she says.

She adds that although these experiences appear to be interesting and enjoyable to a large number of people, it's clear that some who are participating in these services have experienced negative outcomes. "In future research, we'd like to better understand those outcomes and what resources could be helpful in managing them," she says.

Read more at Science Daily