New gene fishing technology
Basel/Madison – Increasingly powerful sequencing technologies are ushering in an era of personal genome sequences and raising the possibility of using such information to guide medical decisions. Genome resequencing also promises to accelerate the identification of disease-associated mutations. But roughly 98% of the human genome is composed of repeats and intergenic (non-protein-coding) sequences. Thus, it is crucial to focus resequencing on high-value genomic regions such as protein-coding exons or regulatory DNA streches surrounding disease genes of interest.
Researchers from the companies Roche and NimbleGen have now combined the capture of such genomic DNA sequences with highly parallel DNA sequencing. With this approach, they enriched 500 Bp-DNA stretches representing about 6,700 genes by a factor of 400, and also improved the performance of the sequencing reads (Nat. Methods 4(11), 903-905). Another group recovered 98% of 200,000 protein-coding exons with a similar protocol (Nat. Methods 4(11), 907-909).
While both groups claim that the new method provides an adaptable route toward rapid and efficient resequencing of any sizeable, non-repeat portion of the human genome, some problems remain unsolved. One of them is bias by the selective amplification of certain target-DNA-samples. Even so, the technique will likely replace current multiplex-PCR protocols, which are more expensive and labor-intensive.