US researchers have shown that 'solution enrichment' followed by next generation sequencing is highly accurate and reproducible. Their findings suggest that large scale population studies could be economically feasible without upfront expenditure for capital equipment.
The team, from the Scripps Institute and Agilent Technologies, sequenced the exons and potential regulatory elements of 622 genes distributed across the genome that are candidate intervals for playing a role in healthy aging.
They also included three contiguous genomic intervals containing variants associated with age-related diseases for a total of 3.6Mb. Using only standard molecular biology equipment and the Agilent SureSelect Target Enrichment System, they were able to call known single nucleotide polymorphisms (SNPs) with 99.7% accuracy, as well as tens of novel variants, the vast majority of them heterozygotes.
The researchers performed the sequencing on an Illumina Genome Analyzer and used SureSelect capture probes in-solution for target enrichment. Their findings are published in the on-line journal GenomeBiology.
The article states that, in recent years, genome-wide association studies have identified 'compelling' associations between more than 350 locations along the human genome and common complex traits. However, a much larger number of samples must be analysed to move beyond statistical associations to pinpoint the exact causes of these traits.
The article explains that current methods of DNA sequencing cost too much for such large-scale population studies. The researchers suggest that next-generation sequencing technologies and their increased capacity have made it feasible to efficiently sequence hundreds of megabases of DNA. However, the current costs for sequencing entire human genomes make this approach prohibitively expensive for population studies.
By comparison, the researchers claim that SureSelect is a very scalable capture method that allows the processing of multiple samples simultaneously. According to the researchers, all that is need in the lab for high-throughput is a 96-well plate, a magnet and a multichannel pipetter.
Agilent concludes that the solution-hybridization-based method can generate highly uniform coverage of sequence targets, which is reproducible across a large number of samples, thus suggesting that large-scale population studies using next-generation sequencing could become economically feasible.
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