German groups improve genetic workflows

IMGM Laboratories and the Center for Human Genetics and Laboratory Medicine to develop workflows for use of 454 Sequencing Systems in human genetics

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PENZBERG, Germany—Two Germany-based sister companies, IMGM Laboratories GmbH and the Center for Human Genetics and Laboratory Medicine Dr. Klein and Dr. Rost, have announced their plans to use the GS FLX System and GS Junior System from 454 Life Sciences, a Roche company, for the joint development of robust and efficient workflows for targeted sequencing applications in the field of human genetics.

"We believe that 454 Sequencing Systems and the Fluidigm Access Array 48.48 System are a perfect match when it comes to amplicon-based targeted resequencing," says Dr. Ralph Oehlmann, director business development at IMGM. "With an average read length of approximately 450 bases, the Roche 454 GS FLX and GS Junior systems are the only true 'long-read' platforms available on the market today. This, in combination with short run times and the option to multiplex samples, provides the flexibility required for most targeted resequencing applications in diagnostics and research."

With Access Arrays, target amplification and library preparation can be combined elegantly in a single step, Oehlmann adds.

"In just under four hours, 2,304 nanoliter PCR reactions can be carried out to convert 48 samples into 48 pools consisting of 48 bar-coded amplicons each," he says. "In addition to rendering general sequencing services, our main focus will be to offer first-class assay development and validation services for the GS FLX and GS Junior platforms."

Of particular interest to the companies are the advantages of the technology for potential diagnostics applications.

"We strongly believe that diagnostic sequencing will rapidly adopt the high-throughput technologies used now for genomic research. Some years ago, we introduced array technologies for molecular karyotyping, and will now address the massive parallel analysis of disease associated gene panels using next generation sequencing," explains Dr. Hanns-Georg Klein, CEO of both IMGM and the Center for Human Genetics and Laboratory Medicine. "The technology will facilitate the molecular diagnostics of clinically heterogeneous diseases, such as cardiovascular, connective tissue or neuropsychiatric disorders involving 20 to 100 different genes. Also, the analysis of multiple genetic risk factors could be more efficiently integrated into prevention programs by the elaboration of reliable genetic criteria for high-risk individuals."

"The characteristics of the GS Junior System bear a high potential for future use in diagnostic applications," states Dr. Bodo Eickhoff, head of sales and marketing for Roche Applied Science Germany. "IMGM's projects will have high value for the further development of the 454 Sequencing Systems in the fields of diagnostics."

454 Sequencing Systems offer long reads and quick run times, Oehlmann notes, both essential factors for diagnostic sequencing. However, before NGS can be implemented into a routine diagnostics workflow, this promising new technology will have to be thoroughly validated to demonstrate an error-free performance. NGS data have to match or exceed the quality of data generated by conventional Sanger sequencing. Sanger-based targeted resequencing is considered to be the gold standard for sequence analysis in medical genetics. Therefore, using NGS instead of Sanger sequencing is merely an extension of a well-known and successful concept, Oehlmann observes.

However, the increase in throughput and the feasibility of sample multiplexing has led to marked reduction in cost per sample. As a consequence, a cost-effective and fast analysis of multiple relevant genes for a given disorder will be available soon, which was out of reach for Sanger-based diagnostics. Other important factors such as the minimum required degree of coverage need to be addressed before such an assay can be used, Oehlmann adds. While the Center for Human Genetics will focus entirely on the development of diagnostic applications, IMGM will offer assay development and validation as well as 454-based sequencing as a service in a quality controlled environment, he notes.

IMGM, one of Europe's leading outsourcing companies, offers advanced genomic services tailored to the needs of customers from pharma, diagnostics, academia and biotech. The Laboratory Dr. Klein & Dr. Rost in Martinsried near Munich was founded in 1998 as a spin-off from the university hospital Grosshadern in Munich. The facility employs 80 staff including 20 molecular biologists.

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