Study Says 'DNA Sudoku' may Revolutionise Genome Sequencing
Researchers at Cold Spring Harbor Laboratory (CSHL) have combined 2,000-year-old Chinese math theorem with concepts from cryptologyto develop what they dubbed as the "DNA Sudoku", because of its similarity to the logic and combinatorial number-placement rules used in the popular game.
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.
The accomplishment is quiet contrary to past approaches that allowed only a single DNA sample to be sequenced at a time.
It also has an upper hand on 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," said CSHL Professor Gregory Hannon, leader of the team that invented the "Sudoku" approach.
With such efficiency, the approach promises to reduce costs dramatically.
The new method has tremendous potential for clinical applications. It can be used, for example to analyse 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 key to the team's innovation is the pooling strategy, which is based on the 2,000-year-old Chinese remainder theorem.
The method is currently best suited for genotype analyses that require only short segments of an individual's genome to be sequenced to find out if the individual is carrying a certain variant of a gene or a rare mutation.
However, with the improvement in sequencing technologies and researchers gaining the ability to generate sequences for longer segments of the genome, Hannon envisions wider clinical applications for their method such as HLA typing, already an important diagnostic tool for autoimmune diseases, cancer, and for predicting the risk of organ transplantation.
The report will be published as the cover story in the July 1 issue of the journal Genome Research.