May 5, 2016
The human leukocyte antigen (HLA) system is one of the most exciting regions of the genome. Research suggests it is responsible for alerting our immune systems to infected, malfunctioning, and foreign cells. As Alex Lindell, Associate Director, Market Development for HLA at Illumina explains, next-generation sequencing (NGS) is being used to understand the genetics of the HLA region to help scientists develop a deeper understanding of its importance.
What is the HLA system and why is NGS critical to our understanding of it?
HLA plays a large role in the body’s ability to recognize invasive cells and mount an immune response thus helping to fight disease and maintain overall health. It’s highly important, but not as well-studied as many other parts of our DNA because it is the most polymorphic region of the genome, meaning that there are more unique HLA sequences in the human population than in any other family of genes. It also has high levels of sequence homology, meaning identical sequence from gene to gene, which is one of the reasons it is difficult to sequence with older sequencing technologies.
These characteristics make the HLA region one of the most difficult parts of the genome to investigate. It’s been hard to develop tools to aid in widespread analysis of the connection between HLA genetics (often called HLA type) with various types of health outcomes. Because NGS can be used to accurately identify the exact DNA sequence of HLA genes, the introduction of this technology is opening the door to further study of HLA’s role in disease.
How has HLA been studied in the past, and what has that information been used for?
HLA typing, via conventional methods*, has most commonly been used to match organ, bone marrow, and stem cell transplant recipients and donors to try to avoid transplant rejection. However, the complexity of these methods limited their use to life-or-death decisions in transplant and adverse drug response. Widespread studies of HLA have not been possible to the degree needed to enable a broader understanding of the role of HLA in the myriad of human conditions it is believed to impact.
With increased study, what are other areas where knowledge of HLA type could make a difference?
HLA mutations have been associated with almost all autoimmune diseases—diseases in which the immune system mistakenly attacks our own tissues. These diseases include multiple sclerosis, rheumatoid arthritis, type 1 diabetes, celiac disease, ankylosing spondylitis, Graves’ disease, lupus, Crohn’s disease, narcolepsy, psoriasis, and more.
HLA also has a significant role in HIV as certain HLA alleles appear to be protective against HIV and other alleles appear to predispose to HIV. Furthermore, people with certain HLA alleles will have an adverse reaction to abacavir, an HIV antiretroviral drug.
Does HLA Type play a role in response to any other drugs?
HLA is believed to affect response to many medicines including antibiotics, antipsychotics, anticonvulsants, antivirals, anticoagulants, nonsteroidal anti-inflammatory drugs, and even commonly used medicines like aspirin.
Does it have any other uses?
Surprisingly, HLA has been associated with mate selection. Studies have shown that both humans and mice preferentially select mates with HLA types different from than their own. The science behind why is not well understood, but it makes sense from an evolutionary perspective that parents with diverse HLA types would have more genetically diverse offspring that would be more able to fight disease.
What NGS tools does Illumina offer to aid in the study of HLA and its effects on human health?
Illumina has launched the research use only TruSight HLA v2 Sequencing Panel and the Assign 2.0 analysis software. This DNA-to-report solution provides unambiguous sequencing of the HLA genes in less time, reducing hands-on time and sequencing to enable high-resolution HLA typing in less than 48 hours.
*Conventional methods of HLA typing include serology, sequence-specific oligos for each known HLA allele, sequence-specific primers that are PCR-based and analyzed with amplification on gels, and sequence-based typing using Sanger sequencing methods.