In the push to inventory human genetic variation, Utah continues to play a prominent role.
A landmark report published Thursday describes the first attempt to map genomes across human populations, opening new pathways for researchers to explore the mysterious interplay between genes and disease.
One-third of the 179 genomes sequenced for the study came from Utahns who provided blood samples for a database designed to help scientists understand how genetic mutations are passed between generations. The Utah collection, derived from 40 large families in the 1980s, has, for years, played a vital role in the quest to understand how genes work, said Lynn Jorde, chairman of the University of Utah's human genetics department.
"Their DNA has been preserved and used by thousands of investigators," said Jorde, a senior author of the cover article in Nature, a top science journal. "It's so valuable that people keep coming back to it." The new report emerges from an international effort to characterize and catalog the most common genetic mutations. This massive undertaking is made possible by technological breakthroughs that enable scientists to quickly sequence the 3.2 billion pairs of chemicals that make up a person's genome, the complete genetic blueprint stored in cells' nuclei.
"When it started three years ago, it was a much bigger task then than it is now," said Jorde, president-elect of the American Society of Human Genetics. "The sequencing machines are so much faster and far cheaper. If you consider there was a human genome sequenced in 2007, it cost $100 million. Now we're doing them at $10,000 apiece. A few years ago, it was unthinkable. It shows how rapidly this technology has evolved."
Understanding variations • Among the many intriguing findings was evidence that natural selection appears to be having an impact on whether mutations are passed between generations, indicating that humans are still evolving, Jorde said.
Mutations are random mistakes in the genetic code, occurring when DNA copies itself and pairs the wrong chemicals. Most have no effect, but some can cause harm, while others can convey some kind of advantage that helps drive evolution and broaden genetic variation.
The new report was the pilot phase of the 1,000 Genomes Project, a collaboration among investigators from 100 organizations seeking to sequence genomes of thousands of people from 27 populations around the world. Jorde serves on its steering committee.
Some 2,700 genomes have been sequenced so far, and by the end of next year, that number will exceed 30,000, Nature reported.
Thursday marked the project's first public release of data, which will be made available to advance biomedical researchers.
The key to unraveling the relationship between genes and disease requires identifying common genetic variants, those appearing in more than 1 percent of the populations studied, said Harvard endocrinologist and geneticist David Altshuler, a lead investigator in the 1,000 Genomes Project.
"Following the genetic contributors to disease can be a powerful tool to discover new clues about the genes and underlying biological basis for disease, both rare and common. A more complete understanding will require knowing the entire genome sequence of individuals and populations and the routine deployment of this information in medical and clinical research," said Altschuler at a news conference. Altschuler founded Harvard's Broad Institute, where he now directs its Program in Medical and Population Genetics.
One of the report's key components looked at three groups of up to 60 individuals, each representing a continent: the Utahns for Northern Europe, Nigerians for Sub-Saharan Africa and Japanese and Chinese for Eastern Asia.
Nonhereditary diseases have complex causes, featuring an interplay between gene groupings, environment, behavior and chance, Altschuler said. Researchers hope population-scale genomic mapping will shed light on mutations associated with specific diseases, but much work remains to be done.
"What is truly exciting is to live at a time when we have the tools and methods to answer these questions through actual empirical data, rather than speculation," Altschuler said. "For the first time, we are making progress, or at least homing in on the many genes that contribute to each disease."
Thursday's report marked the third time this year Jorde's lab participated in groundbreaking studies. One detected the genetic basis for Tibetans' ability to thrive at high elevation, while another sequenced the genomes of an entire Utah family.
The latter study helped the lab estimate the rate of genetic mutation from one human generation to the next. Jorde's team concluded that people inherit 60 mutations, on average 30 each from their mother and father.
To Jorde's relief, the new study, which relied on a much larger data pool, confirmed that rate.
1,000 Genomes Project
A report published Thursday in Nature describes the first public release of data from an international project to catalog human genetic variations around the world. A database of genetic material from dozens of Utah families provided one-third of the samples used in the first attempt to map the human genome across populations.