Abstract
The meaningfulness of genomic research depends on the accuracy of the reference sequence. NHGRI plays a major role in improving and maintaining this essential resource, dating back to the first draft of the human genome in 2001.
“We can't really have a single reference sequence,” says NHGRI Director Eric Green. While the goal of the Human Genome Project was to produce a single reference sequence, Green says a single reference sequence representation is completely inadequate.
“You must have a reference sequence that properly matches the ancestral origins of a given person. A lot our genomic variations are highly specific to ancestral groups, geographical origin, the history of human migrations and the history of the human species. Historical circumstances have led to populations and subpopulations accumulating certain variants that don't even exist in other populations. There are some disease-causing mutations that are highly prevalent because when they are present in only one copy, they have protected people against other deadly diseases, such as the sickle cell mutation protects against malaria.”
The greatest power will come from maximizing heterogeneity and population diversity. “Genetic and nongenetic studies are really biased toward certain populations. European ancestries are most represented by race and ethnicity,” says Joshua Denny, CEO of the NIH's All of Us Research Program. “Anyone can volunteer for the All of Us program. We have put our effort into reaching and engaging with diverse populations.”
While genetic ancestry is part of diversity, Denny says many other factors—culture, religious belief, location, sexual and gender minorities, socioeconomic status, education—have strong influences on health. “You want to understand the interaction of genetics and environment, the lifestyle, on health outcomes. That includes what treatments people get, the environmental exposures they have and their habits—all those things in those measures of diversity are part of the better way of representing what the true causal elements might be on someone's health.”
