New Study Sheds Light on Genetic Regulation of Immune Function in the Indonesian Archipelago
October 2024 - In a recent study published in The American Journal of Human Genetics, we have revealed the impact of genetic diversity in the Indonesian archipelago on alternative splicing, a crucial process that regulates gene expression and protein variation. Through this research, we gain a new understanding of how genetic variations affect human immune responses, paving the way for exploring disease susceptibility in diverse populations.
The study, led by a team of international scientists, including Dr Pradiptajati Kusuma, Dr Safarina G Malik, and Dr Herawati Sudoyo, from the Mochtar Riady Institute, analysed matched Whole Genome Sequences and Whole Transcriptome Sequences from 115 individuals spanning three major island populations in Indonesia, representing the ancestral polars in the region. By focusing on alternative splicing, we mapped over 6,000 genetic variants, known as splicing quantitative trait loci (sQTLs), some of which were unique to Papuan-like genetic ancestry.
“Indonesia is one of the most genetically diverse regions in the world, and yet it has been underrepresented in genetic studies,” said Dr Kusuma. “Our findings highlight the importance of including more diverse populations in genetic research to better understand human health on a global scale.”
One of the study’s major findings is the role of these genetic variants in regulating immune-related genes. The researchers identified multiple sQTLs associated with the regulation of genes involved in immune responses, including DNM3, a gene linked to membrane trafficking and immune cell development. Many of these variants were not found in European populations, pointing to the unique genetic architecture of the Indonesian archipelago.
“Our results emphasise the need for broader genetic studies across underrepresented populations,” said Dr. Irene Gallego Romero, co-lead author of the study. “By expanding our research to diverse groups, we can better understand how genetic variation influences complex traits and diseases like cancer and autoimmune disorders.”
Furthermore, this study provides opportunities for future research to explore the impact of these genetic mechanisms on health disparities and disease prevalence among various populations. As genetic research broadens its scope to incorporate diverse populations, it can bring about healthcare solutions that are personalised and highly effective on a global scale.
This work highlights the critical role of genetic diversity in shaping gene regulation and immune function in one of the world’s most diverse regions, providing a foundation for future studies on health and disease across global populations.
For more information, contact: Pradiptajati Kusuma, PhD [email: pradiptajati.kusuma@mrinstitute.org]
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