454 Life Sciences, with Yale University researchers, has developed a method using the Genome Sequencer system to identify significant human genetic variability with an unprecedented level of detail
The new method enables researchers to analyse genome-wide structural variations (SV), the gross changes to the genetic code in a very fast and economic way.
The study, entitled 'Paired-end mapping reveals extensive genomic structural variation in humans', appears online (ahead of print) in the journal Science.
Previous studies of human genomic variation tended to look at changes called single nucleotide polymorphism, variations that involve just one nucleotide, commonly referred to as SNP ('snips').
However, the study published today suggests that structural variation is responsible for a larger number of differences between the genomes of two individuals than SNPs.
Furthermore, structural variation may have notable physical effects on an individual.
The role that SV plays in human variability has not been well understood because of cost-prohibitive and imprecise technology used in previous research.
The novel approach described today in Science, called paired end mapping (PEM), used 454 Sequencing to comprehensively study SV at an unmatched level of resolution, detecting most of the structural variation in the human genome.
"454 Sequencing enabled us to efficiently identify over 1000 structural variations in two individuals.
"Our study demonstrates that a large number of SVs are present in the human population and that SV plays a greater role in genetic diversity than SNP," explained Michael Snyder, senior author and Lewis Cullman professor of molecular, cellular and developmental biology and professor of molecular biophysics and biochemistry and director of the Yale Center for Genomics and Proteomics.
"The widespread occurrence of structural variation and the observation that many genes are affected, suggests that SV is likely to be a major form of human variation.
"It will be essential to incorporate SV detection in human genome sequencing projects".
Although SVs were found throughout the genome, researchers found that many SVs are concentrated in specific regions or hot spots.
Several of these hot-spots are regions of the genome known to correlate to some genetic diseases such as Velocardiofacial Syndrome, and Williams-Beuren Syndrome.
Furthermore, structural variation may affect gene function by altering the frequency of a given gene, changing its structure, or alter how the gene is regulated.
"454 Sequencing can generate hundreds of thousands of long read pairs that are unique within the human genome to quickly and accurately determine genomic variations," explained Michael Egholm, co-author of the study and vice president of research and development at 454 Life Sciences.
"This highly accurate study of human genomic structural variation along with the recently sequenced genome of Jim Watson confirms that 454 Sequencing is the first affordable technology to offer a comprehensive view of the human genome".
454 Life Sciences develops and commercialises novel instrumentation for high-throughput DNA sequencing.
Specific applications include whole-genome sequencing, RNA analysis and ultra-deep sequencing of target genes.
The hallmarks of 454 Sequencing are its simple, unbiased sample preparation and massively parallel sequencing, which makes large-scale scientific projects feasible and more affordable.
During the last months, the technology proved its suitability in a lot of application examples, in cancer research, infectious diseases research, drug discovery, marine biology, anthropology, paleontology, and many more.
