Can a new tool unlock the genetic complexity of lupus?
Autoimmune diseases can be triggered by a variety of factors, including genetic predisposition, viral infections, and environmental exposures. When it comes to genetics, researchers continually search for immune-related genes that contribute to autoimmunity. What makes autoimmune diseases more complicated than other genetic conditions (which generally involve one or two mutations) is that there are usually a myriad of genes involved in the development of the conditions that are also influenced by environmental triggers.
In South Korea, researchers developed a high-resolution genetic analysis tool in order to decode complex immune-related gene clusters that are linked to diseases like lupus. In collaboration with the National Institute of Health's genome research department, Hanyang University and Kyung Hee University studied the Major Histocompatibility Complex (MHC) region of the DNA. This part of our genetic code plays a key role in controlling the immune system and contains genes suspected of having links to autoimmune diseases, like HLA and C4.
With this new tool, researchers "can now accurately and easily analyze [the MHC] region. This creates a foundational infrastructure that could be used to uncover genetic causes of not only lupus, but also other autoimmune diseases like rheumatoid arthritis and inflammatory bowel disease,” according to Professor Bae Sang-cheol, who led the study.
Researchers are using this new tool to collect and analyze MHC genes from a large dataset of the general population. This dataset is called an imputation reference panel, which creates a library of genetic information from the population and essentially maps out known genetic variations. By looking at the MHC imputation reference panel, researchers will then be able to compare the panel to the genes of lupus patients to infer what is different and what genes may be playing in the development of lupus.
A second significant impact of the tool is that it may allow for precision medicine. The tool may be used to identify individual variations in immune-related genes and offer targeted treatments. Professor Bae explains that "if we identify that a patient’s disease is linked to the C4 gene—one of the strongest known genetic risk factors—we can choose a drug that specifically targets that mechanism."
“Autoimmune diseases are even more complex than cancer because the genetic combinations vary so much from person to person. But if we can sort people by their genetic profile and match them with the right drugs, it could open doors to more precise treatments for everyone.”
Finally, this panel of data is unique in that it was collected from the South Korean population, representing a diverse set of genetic data. In the past, most panels have been developed from the population in the United States. Now that there is a panel that includes East Asian-specific genetic variations, there is increased precision for different populations. The panel will also be made available through Korea's national CODA system, which is accessible to researchers all over the world.
