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More insights about Solexa resequencing magic

The cost of resequencing a human genome has been estimated at more than $15 million, and would require 50 current state-of-the-art capillary electrophoresis machines operating 24 hours a day, for seven days a week, for a year, explains Rubinstein. Thus, the scale of resequencing, the high accuracy required, and the difficulty with sequencing some kinds of DNA such as homopolymers are some of the challenges faced by conventional and upcoming sequencing technologies.

?We believe,? she says, ?that our BAC sequencing results demonstrate that we will be able to achieve throughput of the scale required to resequence a human genome, and that our technology will be able to address the complexities of human DNA sequences.?

Using 25 base pair reads, Solexa scientists uniquely aligned 90% of the BAC back to its own reference sequence, correctly identified 100% of the 153 polymorphisms in the sequenceable regions, and sequenced the DNA with greater than 99.99% accuracy, according to Rubinstein.

The scientists also sequenced 99% of homopolymers in the sequenceable regions, thus showing that the platform could handle more problematic DNA se-quences. This included repeats of up to 31 base pairs, successfully resequencing of all dinucleotide repeats in the BAC, attaining relatively uniform sequencing coverage with minimal correlation to base composition, and establishing the absence of systematic sequence context-related errors, says Rubinstein.

?Ours is the only emerging sequencing technology to demonstrate these results,? she claims. This is because of the Solexa- developed reversible terminator chemistry that uses a sequencing by synthesis approach that discerns the sequence of a DNA molecule one base at a time, she explains.

Solexa is in the process of validating the chemistry and informatics on the prototype of the instrument intended for sail.

?We expect to complete this validation in time to introduce the system to the market by the end of 2005. We anticipate commercial sales of the instrument beginning in the first half of 2006,? says Rubinstein.

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