Landmark Genotyping Study Demonstrates the Power of 454 Sequencing Systems for Immunogenetics

Tue Oct 13, 2009 8:00am EDT
 
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BRANFORD, Conn.--(Business Wire)--
A study published online today in the prestigious Nature Medicine journal
reports that researchers at the Wisconsin National Primate Research Center have
explored a new high-throughput method for decoding one of the most critical
genomic regions for the immune system. In the study, they used ultra-deep
sequencing with the Genome Sequencer FLX System from 454 Life Sciences, a Roche
Company (SWX:RO) (SWX:ROG) (Pink Sheets: RHHBY), to perform rapid major
histocompatibility complex (MHC) class I genotyping in macaques, a common model
primate. The MHC is a gene-rich portion of the human and monkey genome that
plays a critical role in the immune system. Robust genotyping methods are
essential for studies of the T cell response, including research on autoimmune
and infectious disease, transplantation, and vaccine development. 

Genotyping efforts in nonhuman primates using existing technologies have
frustrated research efforts for more than a decade due to the extreme complexity
of this genomic region in macaques, even compared to humans. Importantly, the
study demonstrates that the state-of-the-art 454 Sequencing System can
dramatically improve upon traditional Sanger sequencing methods by enabling the
discovery of new genotypes that had previously been missed. In the initial
study, the Wisconsin researchers were able to characterize MHC genotypes in 48
individual monkeys in a single instrument run. They identified, on average, 22
distinct MHC class 1 transcript sequences in each monkey, demonstrating how much
there is to uncover about immune response in these important model species. 

"Comprehensive MHC genotyping has the potential to revolutionize the use of
nonhuman primates in infectious disease and transplantation research and to
guide functional immunology studies," explained Dr. Roger Wiseman, lead author
at the Wisconsin National Primate Research Center. "The abundance of long
sequencing reads generated by the Genome Sequencer FLX System are critical for
resolving closely related alleles, a truth that is becoming increasing clear as
we begin to generate 500 base pair amplicons using the early-access GS FLX
Titanium Series amplicon sequencing kits and software." 

The best known genes in the MHC region are the human leukocyte antigen (HLA)
genes, which encode for the cell-surface proteins responsible for
differentiating between self and non-self cells and other antigens.
Understanding an individual`s HLA genotype is particularly important in matching
donors and recipients in tissue transplantation since any cell displaying a
non-self HLA type causes immunological rejection. 

Perhaps the most exciting aspect of the study is its application to future
immunologic genotyping efforts in humans. Not only does the new sequencing
method offer much more comprehensive genotyping compared to existing
technologies, it also may prove to be a cost effective solution. "Based on the
yield from our macaques studies, we predict that HLA class I genotypes for
thousands of individuals could be generated in a single Genome Sequencer FLX
System run," said Dr. David O`Connor, senior author, Associate Director of the
Wisconsin National Primate Research Center and Assistant Professor at the
University of Wisconsin-Madison. "We may soon be looking at a time where all
donor samples in tissue registry programs are analyzed with the 454 Sequencing
System." 

"This study shows the tremendous potential of 454 Sequencing Systems to
fundamentally change the way we study the immune system and T cell response in
human disease research," said Michael Egholm, Chief Technology Officer and Vice
President of R&D at 454 Life Sciences. "Rapid MHC genotyping and analysis of the
VDJ antibody repertoire represent two critical ways in which the technology is
opening new doors in the field of immunogenetics." 

For more information on 454 Sequencing technology, go to www.454.com. 

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world`s leading
research-focused healthcare groups in the fields of pharmaceuticals and
diagnostics. As the world`s biggest biotech company and an innovator of products
and services for the early detection, prevention, diagnosis and treatment of
diseases, the Group contributes on a broad range of fronts to improving people`s
health and quality of life. Roche is the world leader in in-vitro diagnostics
and drugs for cancer and transplantation, and is a market leader in virology. It
is also active in other major therapeutic areas such as autoimmune diseases,
inflammatory and metabolic disorders and diseases of the central nervous system.
In 2008 sales by the Pharmaceuticals Division totalled 36.0 billion Swiss
francs, and the Diagnostics Division posted sales of 9.7 billion francs. Roche
has R&D agreements and strategic alliances with numerous partners, including
majority ownership interests in Genentech and Chugai, and invested nearly 9
billion Swiss francs in R&D in 2008. Worldwide, the Group employs about 80,000
people. Additional information is available on the Internet at www.roche.com. 

(1) Wiseman et al. MHC genotyping with massively parallel pyrosequencing. (2009)
Nature Medicine. (DOI 10.1038/nm.2038). 

The 454 Genome Sequencer FLX System is sold for life science research use only. 

454, 454 SEQUENCING, 454 LIFE SCIENCES and GS FLX TITANIUM are trademarks of
Roche.

Roche Diagnostics
Dr. Burkhard Ziebolz
Phone: +49 8856 604830
Email: burkhard.ziebolz@roche.com
or
454 Life Sciences Corporation, a Roche company
Dr. Ulrich Schwoerer
Phone: 203-871-2300
Email: ulrich.schwoerer@roche.com



Copyright Business Wire 2009

 

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