Unlocking the Secrets of Immunogenetics with Dr Charles Khor
Curious about the genetic secrets behind disease susceptibility? In this exclusive interview, we chat with Dr Charles Khor, senior research fellow at SCELSE, who is unlocking the mysteries of immunogenetic genes through cutting-edge bioinformatics. Under the guidance of Assistant Prof Kim Hie Lim, Dr Khor's work taps into whole genome sequencing data, focusing on underrepresented populations in Asia as part of the GenomeAsia 100K project.
Dr Khor holds a PhD from the University of Tokyo and has experience as an assistant professor at both the University of Tokyo and the National Center for Global Health and Medicine (NCGM) in Japan. He sheds light on his research and the pivotal role of Human Leukocyte Antigen (HLA) genes in understanding disease susceptibility.
1. Can you explain the significance of the human genome in our health?
Dr Khor: The human genome, which consists of 3 billion DNA base pairs, essentially functions as a detailed instruction manual for our bodies. It determines everything from our physical traits, like eye colour, to our susceptibility to diseases. Over generations, our genome has adapted to help us combat life-threatening infectious diseases such as HIV, tuberculosis, and even more recent threats like COVID-19. Our immune system is a direct product of this evolutionary process.
2. What exactly are Human Leukocyte Antigen (HLA) genes, and why are they so important?
Dr Khor: HLA genes are located on chromosome 6 and are among the most variable genes in our genome. Their variability allows our immune system to recognise and respond to a vast array of internal and external threats. HLA genes are responsible for identifying foreign invaders, like viruses or bacteria, and triggering the appropriate immune response. This diversity in HLA genes is critical for protecting us from infections and diseases.
3. How do HLA genes contribute to disease susceptibility?
Dr Khor: By comparing the frequencies of HLA alleles—different versions of HLA genes—between healthy individuals and those affected by specific diseases, we can identify which alleles are linked to a higher disease risk. For example, carrying the DQB1*06:02 allele increases the risk of developing hepatocellular carcinoma in patients with hepatitis C in the Taiwanese population (Fig. 1). We've also found that individuals with certain HLA alleles are more likely to experience severe symptoms of COVID-19. HLA alleles play a significant role in susceptibility to a range of diseases, from autoimmune conditions to infectious diseases.
4. How do researchers like yourself identify these connections between HLA alleles and diseases?
Dr Khor: We use DNA sequencing technologies such as Sanger sequencing and Next-Generation Sequencing (NGS) to study entire genes and pinpoint variations in HLA alleles (Fig. 2,3). By comparing these variations in people with and without certain diseases, we can identify specific alleles that may increase the risk of developing those diseases. This research is key to understanding how our genetic makeup influences disease susceptibility.
5. If someone carries a specific HLA allele, does that mean they will definitely develop a certain disease?
Dr Khor: Not necessarily. Carrying a particular HLA allele indicates an increased risk, but it doesn’t guarantee that the person will develop the disease. It’s more about understanding probabilities and risk factors. Knowing which HLA alleles an individual carries can help with early detection and personalised healthcare, but it’s not a black-and-white predictor.
6. What are the broader implications of your research on HLA genes for public health?
Dr Khor: Our research helps build a deeper understanding of the immune system and its role in fighting diseases. By identifying HLA alleles associated with certain diseases, we can contribute to developing targeted treatments and personalised medicine strategies. This knowledge is particularly important for populations that have been historically underrepresented in genetic studies, like many Asian populations. The more we learn, the better equipped we are to address global health challenges.