- Posted Sunday September 14, 2008
Identification of genetic variants using barcoded multiplexed sequencing
PHOENIX, Ariz. - Sept. 14, 2008 - Investigators at the Translational Genomics Research Institute (TGen) today announced a faster and less expensive way for scientists to find which genes might affect human health.
Using bar-codes, not unlike what shoppers find in grocery stores, TGen researchers found a way to index portions of the nearly 3-billion-base human genetic code, making it easier for scientists to zero in on the regions most likely to show variations in genetic traits.
The findings were published today in the online version of the journal Nature Methods. The study will be published in print in the journal's October edition.
Dr. David Craig, associate director of TGen's Neurogenomics Division, said the new method should cost only one-tenth, or less, of the current cost of sequencing genes commonly done to analyze Single Nucleotide Polymorphisms (SNPs), and in performing Genome-Wide Association (GWA) studies.
"Our goal is to find the genetic basis of disease," said Craig, the study's lead author. "It (the new method) provides us a way to immediately use next-generation sequencing technology for studying hundreds to thousands of individuals."
John Pearson, the head of TGen's Bioinformatics Research Unit, said the new method would allow scientists worldwide to more easily tune their sequencing experiments, and conduct their experiments with greater speed.
"In many cases, rather than sequencing the whole genome for 10 people, researchers would rather sequence a dozen genes for 1,000 people," said Pearson, who contributed to the study.
TGen scientists adapted an exciting new technology known as "next generation sequencing" to allow samples to be run and analyzed using 15 well-characterized indexes.
"Moving forward, TGen scientists are now attempting to merge this indexing approach with sequence-capture methods currently under development in their laboratories, which would likely further improve the cost savings and speed," said Dr. Matthew Huentelman, an investigator in TGen's Neurogenomics Division, who also contributed to the study.
Depending on assumptions made in an experiment, the desired coverage -- and as a consequence, the cost -- can vary substantially, the study said, depending on whether the objective is:
Discovering genetic variants for genotyping by a separate method such as custom SNP genotyping.
Conducting polymorphism discovery and variant calling within one sequencing experiment.
Exhaustively resequencing for all common and rare
The new method of analyzing human genetics should enable scientists at TGen and elsewhere to push ahead with key scientific research needed to prevent, diagnosis and treat a variety of diseases and conditions.
"Although whole-genome sequencing may be the primary motivator for improvements in sequencing technology," the study said, "it is clear that next-generation technologies are immediately useful for focused, hypothesis-driven sequencing of linkage peaks, groupings of candidate genes or sequencing the entire known coding sequence of the human genome."
The Translational Genomics Research Institute (TGen) is a non-profit organization dedicated to conducting groundbreaking research with life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process.
The Translational Genomics Research Institute