In genetics, pedigrees are important for a lot more reasons than you might think.
It is not just about creating family trees or seeing how individuals in a family are related. Pedigrees are also useful for studying diseases and understanding broader questions about family structure and how people marry and migrate. They can also potentially be used to find out facts about long-dead ancestors, such as their phenotypic traits and where they came from.
A New Method Called Bonsai
Researchers at 23andMe recently created a new method for inferring large human pedigrees. Published in the American Journal of Human Genetics, this new method, dubbed Bonsai, uses a new algorithm to build very large pedigrees. These new methods can quickly and efficiently assemble small pedigrees into a larger family tree that shows degrees of separation between individuals.
These pedigrees can also help in studying the link between genetics and disease. Pedigrees can be helpful, especially when a disease is rare. In Genome-Wide Association Studies — a common method for discovering the genetic factors related to a common phenotype or disease — scientists must thin their sample to remove close relatives. Or they must leverage known relationships in order to increase the number of subjects that can be included, and thus the statistical power for detecting associations. If full pedigrees are known, it opens the door for using a broader range of statistical methods. This in turn can be used to detect disease association and discover so-called de novo mutations that occurred for the first time in a family member.
The ability to construct very large pedigrees is also useful for genealogy. In particular, the ability to use genetic data to infer pedigrees can help
bridge gaps in historical records. It can help detect places where the historical records may be inaccurate. By using the rules of Mendelian inheritance in reverse, it’s even possible to assign present-day alleles to the ancestors they came from. Thus making it possible to know the genotypes carried by long-dead ancestors. When these alleles are associated with phenotypes or ancestry from a particular population, it’s possible to make educated guesses about the physical traits of ancestors. One could use the same method to find out where they came from.
23andMe’s new Bonsai method improves existing methods for building really large pedigrees. It also opens up other possibilities as well, said Ethan Jewett, Ph.D., a 23andMe population geneticist working on probabilistic methods and lead author of the paper.
“Big pedigrees make it possible to explore questions about family structure,” Ethan said. “Like how common a certain type of relationship is in a given population, like double cousins, for instance.”
Pedigrees inferred from DNA allow researchers to look at other issues as well. It could help determine how often a self-reported pedigree agrees with an inferred pedigree. In other words, it can let us know how well people know their family trees. The paper found several instances of self-reported family trees that have at least one relationship misidentified.
There are other larger population-level insights researchers can learn from these large pedigrees. For example, the method allows researchers to determine the ancestry composition of the average pedigree in the United States, traced back several generations. Another example the method could help answer questions like how often do people have kids with people outside of their cultural or ancestral group. This work can also help improve our understanding of the age distributions for different types of relationships, such as parent-child, or grandparent-grandchild, or first cousins. That ultimately can help in 23andMe’s ability to predict relationships. Understanding those relationships can also offer insights into human history and disease.
This new method improves both the efficiency and accuracy of building large and complex human pedigrees.
You can read more about the method here.