Hutch News

Tissue-typing lab often produces discoveries

May 3, 2001

If you wanted to work in a conventional clinical laboratory, the Seattle Cancer Care Alliance Clinical Immunogenetics Lab would not be for you.

"Typical clinical laboratories have very well-defined predictable procedures and results," said Dr. John Hansen, head of the Hutch's Immunogenetics Program.

"But because of the nature of HLA (human leukocyte antigen) typing, the Clinical Immunogenetics Laboratory has to be prepared to resolve ambiguous results and follow up with more detailed analytical work that frequently ends with discovery of new HLA variants.

"That's an unusual position for a clinical lab to be in, but it is exciting, rewarding work."

HLA genes, which specify an individual's tissue type, lie within the most variable region of the human genome, known as the major histocompatibility complex (MHC). MHC DNA controls an enormous array of immune-system functions, including susceptibility to autoimmune and other disorders.

Analysis of genetic diversity in the MHC and other regions of the human genome is critical to understanding the role that genetics plays in predisposition to numerous disease.

So for scientists interested in studying genetic variation, laboratories like the Clinical Immunogenetics Laboratory are gold mines for the discovery of new HLA alleles, or variants.

"The Clinical Immunogenetics Lab sees much more genetic diversity than most research labs dedicated to studying HLA genes," Hansen said.

Anajane Smith, lab manager, said her group regularly discovers new HLA alleles.

"We find new or rare Class I alleles in about 5 percent of our patients," she said, "and we regularly discover new Class II alleles. We keep a database of this information, which helps us predict the likelihood that a new patient will find a donor."

Detailed analysis of new alleles is done by DNA sequencing, using automated sequencers in the Clinical Immunogenetics Laboratory.

Hansen, who heads an international effort to characterize variation in MHC DNA, said a database of alleles is being used by anthropologists to catalogue human diversity and worldwide migration patterns as well as by geneticists interested in diseases known to be affected by HLA genotype.

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