Researchers have long been perplexed by the complex genetics behind chronic inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. In a new paper published in Human Genetics, Mater Researchers have delved into the intricate world of immune cells called macrophages to unlock the causes behind these debilitating diseases.
The research team, led by Macrophage Biology Research Group Leader Professor David Hume AO, Professor Kim Summers and collaborators at the Australian National University, sought to unravel the genetic puzzle behind IBD. Using blood samples from IBD patients, unaffected family members and a control group consisting of healthy individuals, the team developed a system to analyse the ways in which macrophages respond to stimuli derived from microbes in the gut.
Single nucleotide variants (SNVs)—a DNA sequence where a single molecule in the genome sequence is altered—were examined, along with whole genome transcriptome sequencing to uncover the difference in the gene expressions in the IBD patients and the control group.
Prof Hume said these results were then analysed using bioinformatics tools to process and interpret the data.
"What we found was surprising. There were no consistent differences in overall gene activity between IBD patients and the control group. Instead, even within a family, we found very large differences between individuals in the activity of genes that regulate the function of macrophages and the development of inflammation," Prof Hume said.
"These differences included large variations in the activity of genes associated with a group of immune proteins called the HLA complex, which is known to be linked to IBD susceptibility."
These findings shed light on the genetic factors that contribute to whether people are susceptible to IBD or not and provide valuable insights into the intricate interplay between genetics, immune function and environmental triggers that lead to development of disease.
Prof Hume said that this study represents a significant step forward in unraveling the genetic puzzle of IBD.
"We formed the view that each IBD patient may be unique in terms of the molecular basis for their disease susceptibility, which has important implications for understanding variations in response to specific treatments."
The full article, titled The relationship between extreme inter‑individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease was published in the journal Human Genetics in February 2024.
To learn more about Prof Hume, click here.
