International Consortium Announces the 1000 Genomes Project

Major Sequencing Effort Will Produce Most Detailed Map
Of Human Genetic Variation to Support Disease Studies

An international research consortium today announced the 1000 Genomes Project, an
ambitious effort that will involve sequencing the genomes of at least a thousand
people from around the world to create the most detailed and medically useful picture
to date of human genetic variation. The project will receive major support from the
Wellcome Trust Sanger Institute in Hinxton, England, the Beijing Genomics Institute,
Shenzhen (BGI Shenzhen) in China and the National Human Genome Research
Institute (NHGRI), part of the National Institutes of Health (NIH).

Drawing on the expertise of multidisciplinary research teams, the 1000 Genomes
Project will develop a new map of the human genome that will provide a view of
biomedically relevant DNA variations at a resolution unmatched by current resources.
As with other major human genome reference projects, data from the 1000 Genomes
Project will be made swiftly available to the worldwide scientific community through
freely accessible public databases.

“The 1000 Genomes Project will examine the human genome at a level of detail that
no one has done before,” said Richard Durbin, Ph.D., of the Wellcome Trust Sanger
Institute, who is co-chair of the consortium. “Such a project would have been
unthinkable only two years ago. Today, thanks to amazing strides in sequencing
technology, bioinformatics and population genomics, it is now within our grasp. So
we are moving forward to build a tool that will greatly expand and further accelerate
efforts to find more of the genetic factors involved in human health and disease.”

Any two humans are more than 99 percent the same at the genetic level. However, it
is important to understand the small fraction of genetic material that varies among
people because it can help explain individual differences in susceptibility to disease,
response to drugs or reaction to environmental factors. Variation in the human
genome is organized into local neighborhoods called haplotypes, which are stretches
of DNA usually inherited as intact blocks of information.

Recently developed catalogs of human genetic variation, such as the HapMap, have
proved valuable in human genetic research. Using the HapMap and related resources,
researchers already have discovered more than 100 regions of the genome containing
genetic variants that are associated with risk of common human diseases such as
diabetes, coronary artery disease, prostate and breast cancer, rheumatoid arthritis,
inflammatory bowel disease and age-related macular degeneration.

However, because existing maps are not extremely detailed, researchers often must
follow those studies with costly and time-consuming DNA sequencing to help
pinpoint the precise causative variants. The new map would enable researchers to
more quickly zero in on disease-related genetic variants, speeding efforts to use
genetic information to develop new strategies for diagnosing, treating and preventing
common diseases.

The scientific goals of the 1000 Genomes Project are to produce a catalog of variants
that are present at 1 percent or greater frequency in the human population across most
of the genome, and down to 0.5 percent or lower within genes. This will likely entail
sequencing the genomes of at least 1,000 people. These people will be anonymous
and will not have any medical information collected on them, because the project is
developing a basic resource to provide information on genetic variation. The catalog
that is developed will be used by researchers in many future studies of people with
particular diseases.

“This new project will increase the sensitivity of disease discovery efforts across the
genome five-fold and within gene regions at least 10-fold,” said NHGRI Director
Francis S. Collins, M.D., Ph.D. “Our existing databases do a reasonably good job of
cataloging variations found in at least 10 percent of a population. By harnessing the
power of new sequencing technologies and novel computational methods, we hope to
give biomedical researchers a genome-wide map of variation down to the 1 percent
level. This will change the way we carry out studies of genetic disease.”

With current approaches, researchers can search for two types of genetic variants
related to disease. The first type is very rare genetic variants that have a severe effect,
such as the variants responsible for causing cystic fibrosis and Huntington’s disease.
To find these rare variants, which typically affect fewer than one in 1,000 people,
researchers often must spend years on studies involving affected families. However,
most common diseases, such as diabetes and heart disease, are influenced by more
common genetic variants. Most of these common variants have weak effects, perhaps
increasing risk of a common condition by 25 percent or less. Recently, using a new
approach known as a genome-wide association study, researchers have been able to
search for these common variants.

“Between these two types of genetic variants — very rare and fairly common — we
have a significant gap in our knowledge. The 1000 Genomes Project is designed to fill
that gap, which we anticipate will contain many important variants that are relevant to
human health and disease,” said David Altshuler, M.D., Ph.D., of Massachusetts
General Hospital in Boston and the Broad Institute of Massachusetts Institute of
Technology (MIT) and Harvard University in Cambridge, Mass., who is the
consortium’s co-chair and was a leader of the HapMap Consortium.

One use of the new catalog will be to follow up genome-wide association studies.
Investigators who find that a part of the genome is associated with a disease will be
able to look it up in the catalog, and find almost all variants in that region. They will
then be able to conduct functional studies to see whether any of the catalogued
variants directly contribute to the disease.

The 1000 Genomes Project builds on the human haplotype map developed by the
International HapMap Project. The new map will provide genomic context
surrounding the HapMap’s genetic variants, giving researchers important clues to
which variants might be causal, including more precise information on where to
search for causal variants.

Going a major step beyond the HapMap, the 1000 Genomes Project will map not only
the single-letter differences in people’s DNA, called single nucleotide polymorphisms
(SNPs), but also will produce a high-resolution map of larger differences in genome
structure called structural variants. Structural variants are rearrangements, deletions or
duplications of segments of the human genome. The importance of these variants has
become increasingly clear with surveys completed in the past 18 months that show
these differences in genome structure may play a role in susceptibility to certain
conditions, such as mental retardation and autism.

In addition to accelerating the search for genetic variants involved in susceptibility to
common diseases, the map produced by the 1000 Genomes Project will provide a
deeper understanding of human genetic variation and open the door to many other
new findings of significance to both medicine and basic human biology.

The sequencing work will be carried out at the Sanger Institute, BGI Shenzhen and
NHGRI’s Large-Scale Sequencing Network, which includes the Broad Institute of
MIT and Harvard; the Washington University Genome Sequencing Center at the
Washington University School of Medicine in St. Louis; and the Human Genome
Sequencing Center at the Baylor College of Medicine in Houston. The consortium
may add other participants over time.

The project depends on large-scale implementation of several new sequencing
platforms. Using standard DNA sequencing technologies, the effort would likely cost
more than $500 million. However, leaders of the 1000 Genomes Project expect the
costs to be far lower – in the range of $30 million to $50 million – because of the
project’s pioneering efforts to use new sequencing technologies in the most efficient
and cost-effective manner.

In the first phase of the 1000 Genomes Project, lasting about a year, researchers will
conduct three pilots. The results of the pilots will be used to decide how to most
efficiently and cost effectively produce the project’s detailed map of human genetic
variation.

The first pilot will involve sequencing the genomes of two nuclear families (both
parents and an adult child) at deep coverage that averages 20 passes of each genome.
This will provide a comprehensive dataset from six people that will help the project
figure out how to identify variants using the new sequencing platforms, and serve as a
basis for comparison for other parts of the effort.

The second pilot will involve sequencing the genomes of 180 people at low coverage
that averages two passes of each genome. This will test the ability to use lowcoverage
data from new sequencing platforms to identify sequence variants and to put
them in their genomic context.

http://www.1000genomes.org/files/1000Genomes-NewsRelease.pdf