CSHL scientists harness logic of 'Sudoku' math puzzle to vastly enhance genome-sequencing ...( Cold Spring Harbor N.Y. A math-base...)

Cold Spring Harbor, N.Y. A math-based game that has taken the world by storm with its ability to delight and puzzle may now be poised to revolutionize the fast-changing world of genome sequencing and the field of medical genetics, suggests a new report by a team of scientists at Cold Spring Harbor Laboratory (CSHL). The report will be published as the cover story in the July 1st issue of the journal Genome Research.

Combining a 2,000-year-old Chinese math theorem with concepts from cryptology, the CSHL scientists have devised "DNA Sudoku." The strategy allows tens of thousands of DNA samples to be combined, and their sequences the order in which the letters of the DNA alphabet (A, T, G, and C) line up in the genome to be determined all at once.

This achievement is in stark contrast to past approaches that allowed only a single DNA sample to be sequenced at a time. It also significantly improves upon current approaches that, at best, can combine hundreds of samples for sequencing.

"In theory, it is possible to use the Sudoku method to sequence more than a hundred thousand DNA samples," says CSHL Professor Gregory Hannon, Ph.D., a genomics expert and leader of the team that invented the "Sudoku" approach. At that level of efficiency, it promises to reduce costs dramatically. A sequencing project that costs upwards of $10 million using conventional methods may be accomplished for $50,000 to $80,000 using DNA Sudoku, he estimates.

Originally devised to overcome a sequencing limitation that dogged one of the Hannon lab's research projects, the new method has tremendous potential for clinical applications. It can be used, says Hannon, to analyze specific regions of the genomes of a large population and identify individuals who carry mutations that cause genetic diseases a process known as genotyping.

The CSHL team has already begun to explore this possibility via a collaboration with Dor Yeshorim, a New Y
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