New gene database to inform bespoke treatments

A global reference showing the variation of immune system genes across populations will improve personalized medicine and transplant outcomes.

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Increased access to next-generation DNA sequencing is enabling researchers to compile huge databases, revealing human genetic variation around the world. Now, a global collaboration between researchers at 20 blood stem cell donor registries has compiled data on important immune system genes called human leukocyte antigens (HLAs) in more than eight million individuals.

 

HLA genes produce cell surface proteins that bind to pathogens including bacteria, viruses and cancer cells, leading to their destruction. However, there are many variants of these genes, called alleles, which have evolved in the human population through mutations and natural selection.

 

“The different HLA variants interact with different pieces of a pathogen,” explains Carolyn Hurley from Georgetown University, USA, who led the work to compile the database. “This results in variation among individuals in our ability to respond to infection, and our susceptibility to specific autoimmune diseases.” 

 

Understanding these individual variations can help prevent adverse drug reactions, inform immunotherapy approaches, and ensure successful blood stem cell, tissue or organ transplants.

 

“The presence of different HLA proteins on a graft, compared to the patient’s, may result in graft rejection or a destructive immune response,” says Hurley. “Finding a graft donor who shares HLA protein variants with the patient reduces or prevents this.”

 

Previous efforts to compile HLA allele data have been limited by the variety of methods used to collect them, leaving ambiguity about which parts of genes were analyzed, and to what resolution.

 

Hurley and co-workers “addressed these challenges by collecting data from blood stem cell registries that have very large numbers of individuals tested by powerful DNA sequencing methods.”

 

The new HLA database is named the CIWD catalog, because it categorizes alleles based on their frequency of occurrence as ‘Common’, ‘Intermediate’ or ‘Well Documented’. The latter refers to alleles that were observed in at least five unrelated individuals. So, while they may be rare, their existence is not in question.

 

The catalog also places individuals into geographical, ancestral and ethnic groups, enabling researchers to identify which variations are most prevalent in certain populations.

 Hurley’s paper, published in the journal HLA, includes four co-authors affiliated with the Saudi Stem Cell Donor Registry at KAIMRC. “Their contribution helped us understand the HLA profile of individuals in the Middle East,” says Hurley. “The data from the publication will help the registry itself to find the best donor for a Saudi patient requiring a transplant.”

References

  1. Hurley C.K., et al. Common, intermediate and well-documented HLA alleles in world populations: CIWD version 3.0.0. HLA 95: 516-531 (2020). | article

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