StemCell Therapy

A team led by researchers at La Jollas Human Longevity reports developing a faster and more accurate method for determining immune type. The method will speed up immune matching for organ transplant and other purposes such as treating infectious and autoimmune diseases, the scientists say.

The method characterizes a region of the genome called human leukocyte antigen, or HLA, that regulates the immune system. Located on Chromosome 6, this region contains a high number of short, repetitive DNA sequences.

Because these repeats are so similar, placing them in the correct order is difficult. So even when people have their genome sequenced, the precise HLA type may not be clear. People can have HLA typing done separately, but that adds time and expense, said J. Craig Venter, one of the studys authors.

The study was published July 3 in the Proceedings of the National Academy of Sciences. Go to j.mp/humanhla for the study. Venter was senior author. The first author was Chao Xie.

The Human Longevity-led team invented an algorithm called xHLA to read these sequences correctly. Results are available within about 3 minutes from a desktop computer, instead of several minutes or even hours, the study stated. Moreover, the method helps identity potential matches that purely DNA-based methods would miss.

Making HLA typing a routine part of sequencing will help doctors advance the practice of precision medicine, the study stated.

For example, autoimmune disorder patients often have chronic problems with no exact diagnosis for many years after repeated doctor visits, the study stated. Knowing patients HLA types could lead to early diagnosis and reduce the burden on both patients and the healthcare system.

Venter said Human Longevity now offers HLA typing as part of its genome sequencing service. And in the future, this technology will be omnipresent and in the hands of patients.

If a family member needs a kidney transplant, you can just look it up on your iPhone and compare the sequences, and everybody will know immediately if theres a match in the family, or other places, Venter said.

Popular sequencing technologies cut up DNA into short pieces for sequencing. These pieces are reassembled by computer like an electronic jigsaw puzzle. But the many repetitive components in HLA can fool the computer programs, like similarly shaped or colored jigsaw puzzle pieces can do to a human.

The xHLA algorithm works with sequencing technology from Illumina to improve accuracy. An important component of the algorithm is that it examines the sequence of amino acids the DNA codes for, the study said. This helps accuracy by accepting DNA variations that happen to code for the same amino acid.

Since immune compatibility is determined at the protein level, using these synonymous variations produces a more accurate result than typing by DNA alone.

The problem with DNA-level alignment is that it cannot distinguish synonymous from nonsynonymous mismatches, the study stated. For example, it will rank five synonymous mismatches as more dissimilar than a single nonsynonymous one.

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Immune-matching process improved, reports Human Longevity-led study - The San Diego Union-Tribune

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