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Leading the Field
Webinar Showcases High Through-Put HLA Sequencing Platform at CHORI

On May 17, 2011, CHORI scientist Elizabeth Trachtenberg, MS, PhD, presented a webinar to several hundred different international laboratories about next-generation, high through-put sequencing of the human leukocyte antigen (HLA) genes using the Roche GS FLX 454 platform.

"In the past year we have analyzed over 5,000 genotypes, with only a small dedicated laboratory,” says Dr. Trachtenberg. “It’s a huge amount of data that allows us to analyze the role HLA might play in diseases like multiple sclerosis, rheumatoid arthritis, Crohn’s disease, and non-hodgkins lymphoma.”

“We can now produce data four to five times faster than we could before.”



HLA genes are part of an incredibly complex cluster of genes along chromosome number six that are involved in human immunity. The HLA molecules play a key role in modulating the human immune system response. Researchers have focused on HLA for decades in order to try and elucidate their role in autoimmune diseases like diabetes, celiac disease, inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis, to name only a few. Other diseases with HLA associations include infectious diseases like HIV, and cancers. Sequencing HLA is also important for stem cell transplantation, as donors and recipients need to match at HLA in order to avoid immunological complications after transplantation.

Utilizing the next-generation sequencing platform allows clonal sequencing of one molecule and exponentially increases the ability to investigate these complicated and key genes.

"Previous sequencing methods involved sequencing both genes from each chromosome at the same time. Because HLA genes and alleles share between them many of the same sequences, simultaneous analysis results in a great deal of ambiguity," says Dr. Trachtenberg.

“With this new platform, however, we are able to sequence just a single molecule, reducing the ambiguity substantially, and, along with other aspects of the next-generation sequencing, make it about four times faster than conventional sequencing.”

Dr. Trachtenberg's group is one of the first of only four international labs invited to be part of an alpha trial of HLA sequencing using the Roche 454 platform. Dr. Trachtenberg is an author on the first papers published on the new technique, and has subsequently become a world leader in next generation HLA sequencing.

In addition, Dr. Trachtenberg and her lab are studying the interrelationship between the natural killer cell's killer immunoglobulin-like receptors (KIR) and their ligands, or binding partners, the HLA molecules. Like HLA, the KIR gene cluster is incredibly complex and plays a significant, front-line role in the immune response. Dr. Trachtenberg hopes that her research will help to elucidate the role of KIR and HLA in stem cell transplantation and disease.

"In general, we are using these high through-put analyses to look for specific HLA and KIR combinations that predispose or protect an individual from disease," says Dr. Trachtenberg.

Dr. Trachtenberg's Applied Genomics laboratory (the Center for Applied Genomics in the Department of Pathology at the hospital) currently uses about 75 percent of its resources to conduct grant-related sequencing, and about 25 percent for contractual sequencing, providing the high through-put service to other researchers interested in utilizing the revolutionary platform. The laboratory offers a knowledgeable and skilled staff to help with projects, project planning, primer development and sequencing. The lab is also CLIA approved, providing the opportunity for investigators to do clinical trials though the lab. For more information, please contact Dr. Elizabeth Trachtenberg at etrachtenberg@chori.org, or Dr. Kazu Osoegawa at kosoegawa@chori.org.

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Wednesday, October 5, 2011 11:22 AM

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