Charting Genetic Variation Across the Globe

Most genetic differences between people—called variants—are harmless. Some can be beneficial. Others have been linked to diseases and conditions ranging from cognitive problems to susceptibilities to cancer, obesity, diabetes, and heart disease. Understanding how genomic variants contribute to disease can help researchers develop improved diagnostics and treatments, and even new methods of prevention.

The 1000 Genomes Project Consortium was launched in 2008 to learn more about genomic variants in diverse populations. The consortium includes researchers from the United States, United Kingdom, China, Germany, and Canada. NIH, led by the National Human Genome Research Institute (NHGRI), helped fund and direct the project. Two studies published online on September 30, 2015, in Nature, mark its completion. The researchers examined the genomes of more than 2,500 people from 26 populations across Africa, East and South Asia, Europe, and the Americas. All participants consented to have their data released and used by researchers around the world.

In the main study, the investigators identified about 88 million sites in the human genome that vary among people—almost 1 per 30 bases of the genome, which has about 3 billion DNA bases. The vast majority of these, about 84.7 million, were differences in a single DNA building block, called single nucleotide polymorphisms (SNPs). About 3.6 million were short insertions or deletions of DNA sequences. The rest were larger differences in DNA structure.

A typical person’s genome, the researchers found, differs from a reference human genome at 4.1 million to 5 million sites. The greatest genomic diversity the researchers found was in African populations. This is consistent with other evidence that humans originated in Africa and migrated to establish other populations around the world.

In the companion Nature paper, researchers examined rarer structural variants in the genome—defined as variants of at least 50 DNA bases. These can include deletions, insertions, duplications (extra DNA copies), and inversions (DNA sequences changing orientation). They found nearly 69,000 structural variants. Although there are far fewer of these variants compared to SNPs, they contain a disproportionate share of regions that have been associated with specific traits such as disease risk.

“The 1000 Genomes Project was an ambitious, historically significant effort that has produced a valuable resource of human genomic variation,” says NHGRI Director Dr. Eric Green. “The latest data and insights add to a growing understanding of the patterns of variation in individuals’ genomes, and provide a foundation for gaining greater insights into the genomics of human disease.”

“The 1000 Genomes Project has laid the foundation for others to answer really interesting questions,” says main study senior author Dr. Adam Auton of the company 23andMe, recently at the Albert Einstein College of Medicine. “Everyone now wants to know what these variants tell us about human disease.”