(CN) — A founder event — the formation of a new population from a small number of ancestral individuals — can be set off by a dramatic reduction of the original group or migration. These events usually lead to a reduction in genetic diversity and increased risk of disease.
But our understanding of founder events in humans and other species throughout history remains sparse despite all our technological advances. Enter ASCEND — a program that measures the shared DNA between people in a population that allows scientists to map founder events throughout generations in order to aid in the understanding of human history and, significantly, the understanding of genetic disease.
Researchers from the University of California, Berkeley, introduced ASCEND (Allele Sharing Correlation for the Estimation of Non-equilibrium Demography) in a study published Thursday in the journal PLOS Genetics.
“Founder events can harbor disease-causing mutations at high frequency as selection against deleterious variants works less efficiently in founder groups. In contrast, outbred populations usually have these deleterious mutations at very low frequency,” says Rémi Tournebize, a former post doctoral researcher at the Department of Molecular and Cell Biology and the Center for Computational Biology at UC Berkeley, and lead author of the study.
ASCEND tracks the timeline and intensity of founder events by measuring the extent of genetic sharing between members of a bottlenecked population.
“The offsprings of these founder individuals in turn share long blocks in their genome that are inherited identical by descent from these few ancestors,” said Tournebize in an email. “As time passes, these blocks will become smaller due to crossover events that occur during meiosis. The rate of crossovers is well characterized and provides a kind of molecular clock. The ASCEND program compares how large the shared blocks are within individuals in a population to infer back when the individuals might have shared a common ancestor, i.e., when a founder event occurred in the population’s history.”
Tournebize and his co-author Priya Moorjani found that geographical isolation, historical migrations or cultural practices can have significant effects on the pattern of founder events of present-day populations.
The team used ASCEND to confirm prior studies on founder events of Ashkenazi Jews, Finns and South Asians, who have demonstrated high rates of recessive genetic disease as a result of their founder event history.
The study then found that Native Americans, Oceanians, and some South Asian groups have undergone even more extreme founder events than Ashkenazi Jews.
“These populations are particularly interesting from a population genetics and medical genetics perspective to understand the genetic consequences of population bottlenecks,” the study notes, indicating a need for more research toward genetic predisposition to disease in these populations as well.
They found that island groups, on average, have over twice the intensity of founder events than continental groups. The Onge population of the Andaman Islands of India had the most extreme founder event discovered in the study, with a founder event ten times as strong as Ashkenazi Jews. They also touch on the effect of colonization, showing evidence of significant founder events occurring during Native American population decline as a result of European colonization.
The study also expands on Moorjani’s prior research on founder events in India. The study attributes the cultural practice of marrying closely within the community having a possible effect on the prevalence of intense founder events in South Asian populations.
The study also demonstrates the extent of the ASCEND program by applying the method to ancient human groups, and even, to man’s best friend. Founder events for ancient humans were markedly more extreme and seem to correlate with fluctuations in population as lifestyles shifted and populations settled in new areas. By applying ASCEND to roughly 200 different dog breeds, the researchers found that the intensity of founder events varied between types of breeds, with higher estimates in working and non-sporting dogs.
The program, however, is not without its limitations.
“Currently, it only applies to characterizing founder events up to 200 generations before the sample lived which is ~6,000 years. For older events, we find the signal becomes very noisy especially in ancient DNA samples. This might be a feature of limited data or uncertainty in recombination clock. Also, in admixed populations, if the founder event occurred before the admixture it is hard to tell if the founder event occurred in the target or one of the ancestral populations,” said Tournebize.
Compared to other methods of analyzing founder events, ASCEND can more accurately measure relatively recent genome sequences without needing as much data. Future medical research can benefit from this more precise understanding of the age and strength of founder events, allowing scientists to further understand genetic disorders, and possibly, how to treat them.
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