Microarray Sequence Capture Speeds Large-Scale Resequencing of Targeted Genomic Regions
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Researchers at Baylor College of Medicine and Roche NimbleGen Inc. have published details of an efficient and cost-effective method for capturing targeted regions of the genome via NimbleChip™ microarrays in preparation for high-throughput 454 Sequencing™.
The technology, called “sequence capture,” enables fast and accurate enrichment of thousands of selected genomic regions, either contiguous or dispersed, such as segments of chromosomes or all genes or exons. The study, entitled “Direct Selection of Human Genomic Loci by Microarray Hybridization,” appears online (ahead of print) in the journal Nature Methods1.
In light of the success of the current sequence capture technology, Baylor’s Human Genome Sequencing Center (HGSC) has signed on as an early access customer to Roche NimbleGen’s sequence capture technology.
As presented on October 10, 2007, at the J. Craig Venter Institute’s Genomes, Medicine, and the Environment (GME) conference, Roche NimbleGen and 454 Life Sciences, working with Dr. Richard Gibbs, professor and Director of the HGSC, will create a whole-genome human exome (all exons) microarray, with the goal of resequencing the entire human exome.
According to Roche NimbleGen, its sequence capture technology enables high-performance targeting of thousands of specific genes or loci using a single microarray hybridization-based enrichment process. The Baylor study1 used Roche’s Genome Sequencer FLX™ System to sequence the enriched genomic regions for downstream analysis. 454 Sequencing technology is ideal for this targeted sequencing approach because of its long read lengths and highly accurate reads.
“This new technology will replace polymerase chain reaction (PCR) for many purposes,” said Gibbs. “If the aim is to sequence a whole genome for everybody, this is a huge step in that direction.”
The Nature Methods paper published by Baylor1 demonstrates that the sequence capture process is simpler, more accurate, more efficient and more cost-effective than the multiplex PCR that was previously used to prepare genomic samples for sequencing. In one experiment, more than 6,700 exons (the part of the genetic code that together form genes), were enriched and analyzed, as well as contiguous genomic regions of up to 5 million bases. Using the old technology this would have taken at least six months.
"We’re delighted to have an opportunity to collaborate with scientists at Baylor HGSC on the development of this breakthrough technology," said Dr. Stan Rose, President of Roche NimbleGen. "The combination of these two Roche technologies—NimbleGen and 454—has the potential to transform the market for DNA sequence analysis."
