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1000 Genomes Project provides an in-depth look across multiple genomes


1000 Genomes Project provides an in-depth look across multiple genomes

A new international effort – the 1000 Genomes Project – aims to sequence, or spell out, the complete genomes of more than 1,000 individuals, establishing by far the most detailed catalogue of human genetic variation as a tool for medical research.

In 2003, after 13 years of research and a cost of nearly $3 billion, the federal government’s Human Genome Project sequenced — spelled out — the complete DNA code of an entire human genome.

That effort produced a massive amount of data about one person, mapping the more than 3 billion base pairs of alleles that make each of us unique.

But, it was data from just one genome.

What researchers need is genomic data from many people to better understand the variations that form the basis of human health – and human disease.

In another effort, the International HapMap Project (2002-07) studied 269 individuals from across the globe, producing more valuable data about genetic variation, but only in selected areas scanned in each genome.

A new international effort launched in 2008 – the 1000 Genomes Project – aims to sequence, or spell out, the complete genomes of more than 1,000 individuals, establishing by far the most detailed catalogue of human genetic variation as a tool for medical research.

Such research will lay the groundwork for the personal genomics era of medicine, in which people routinely will have their genomes sequenced to predict their individual risks of disease and response to drugs, according to the National Institutes of Health, which is helping fund this study.

The 1000 Genomes Project aims to considerably reduce the time and cost of sequencing individual genomes by using faster and less costly technologies. And TGen is playing a substantial role in guiding this objective.

Dr. David Craig, Acting Director of TGen’s Neurogenomics Division, said the result of this massive project should be a nearly exhaustive accounting of the common genetic changes among healthy individuals.

“If the Human Genome Project provided a blueprint of our genetic code, the 1000 Genomes Project should provide detailed annotation for researchers and clinicians that hopefully translates into vastly improved patient care,” Dr. Craig said.

TGen recently was awarded one of five data processing grants; $1.6 million to fund a data processing pipeline for the 1000 Genomes Project.

As the project ramps up, Dr. Craig led a daylong discussion June 12 at TGen. Included were representatives from UCLA and Life Technologies – collaborators on TGen’s grant – and colleagues from Baylor College of Medicine, Amazon.com, and the Van Andel Research Institute.

To reduce the time and cost of mapping each genome, researchers will rely on new technology, so-called next generation sequencing, which will require highly coordinated collaboration by multiple research groups.

In addition to three other next-generation sequencing platforms, TGen will process data using the SOLiD 3 systems produced by Life Technologies. TGen will help develop software tools for the vast amounts of data that will be generated, while adhering to common data and analytical standards so the results can be accessed by researchers across the globe.

“We have three main goals,” said John Pearson, Head of TGen’s Bioinformatics Research Lab. “Developing tools for monitoring data quality. Developing tools for aligning the data and detecting genetic variation across the genome. And developing a suite of software capable of simultaneous viewing of sequence data across multiple sites for the purpose of quality control and variant inspection.”

Those gathered at TGen agreed that they should: establish a “gold standard’’ of reliability and verification, ensure that – while identities of the DNA donors remain confidential – the sequencing results will be freely available via the Internet, and process the data in a way that is useful not only for academic study but also for commercial applications.

This is the first large-scale project to use the next-generation sequencing platforms for extensive human re-sequencing; machines that produce millions of DNA sequence reads in a single pass at a fraction of the original cost.

The project will include three steps: a detailed scan of six individuals (a mother, father and child from two families); a less detailed scan of 180 individuals; and a scan of exons, or coding regions in the genome, among 1,000 individuals.

Scientists hope that by layering the information, the sequences from the six in-depth scans will fill any gaps in the less detailed scans, providing a comprehensive view of more than 1,000 human genomes.

Dr. John Carpten, Director of TGen’s Integrated Cancer Genomics Division, said TGen’s goal is not only to reduce the time and expense of sequencing individual genomes, but also to process data in a way that leads to the best verifiable results.

“We want to do it right. We’re excited about this new technology and where it’s going, and how we can help patients,’’ Dr. Carpten said. “It’s never been done before.’’

Dr. Craig said that the 1000 Genomes Project should provide researchers with the data they need to make tremendous progress in transforming laboratory discoveries into ways of preventing, detecting and treating common debilitating diseases such as Alzheimer’s, autism, diabetes and many types of cancer.

“Four hundred years after Galileo invented the telescope, and 40 years after landing on the moon, we stand at the threshold of major discoveries into the inner-space of molecular biology that will benefit humankind forever,’’ Dr. Craig said.



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