Atlas of Immune-Related Genome Data Compiled

A genetic database for autoimmune and autoinflammatory diseases has been compiled to help researchers more deeply understand how immune disorders develop. The database is called Immune Cell Gene Expression Atlas from the University of Tokyo (ImmuNexUT) and it is described in a Cell paper published today.

"To understand diseases, a deep comprehension of the function of genetic variants is essential. With this data set, we can connect the data about changes to DNA sequence associated with a disease to genes and cell types that are important for disease pathogenesis," said lead author  Mineto Ota, M.D., Ph.D.

Many prior research projects have compared the full genome sequences of patients with medical diagnoses to those of healthy people. Any DNA sequence variants identified in these genome-wide association studies are then considered "associated" with the disease. Many variants identified in association studies are not located in genes, but rather in regulatory DNA. Experts might know that a portion of DNA is involved in gene regulation, but not understand exactly how or what it does or even what genes it regulates.

To uncover the function of regulatory DNA, the team used expression quantitative trait loci (eQTL) analysis to connect differences in DNA sequence to differences in gene expression. With eQTL data, they could make more informed guesses about the purpose of regulatory DNA sequences, how variants in the regulatory sequence might affect expression of the genes it regulates and how those differences in gene expression cause disease.

The research team sequenced the full genomes of 79 healthy volunteers and 337 patients diagnosed with any of 10 different categories of immune-mediated diseases, including rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis.  Understanding immune-mediated diseases is challenging because although each disease is clinically distinct, there are many overlaps and patients with the same diagnosis may show very different symptoms. "Due to all this diversity, there's a limit to how much you can learn studying one immune-mediated disease at a time. But if we study 10 diseases together, it gives a bigger picture about these types of diseases," Ota explained.