Medical researchers have uncovered new clues about why some Australians develop certain diseases, as well as the "building blocks" for potential future treatments.
Researchers from the Sydney-based Garvan Institute of Medical Research and collaborators led three studies that examined the DNA of 2,000 Australians — recording each person's full genome and measuring gene activity in the 28 different types of immune cells.
Professor Joseph Powell, director of Garvan's Translational Genomics program and UNSW's Institute for Genomics and Health, said the research identified 1,500 genes linked to 16 different diseases.
"We did this for a range of different diseases that were all linked to immune function, so autoimmune diseases, cancers, and inflammatory conditions like Alzheimer's and Parkinson's," he said.
Researchers also identified how DNA variations influence gene activity.
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Powell said they identified 21,000 genes and 180,000 DNA positions that act as a "dimmer switch" to control gene expression.
"This gives us the ability to identify how these DNA spots are controlling the activity of genes and then link that to disease," Powell said.
They also found DNA that "turned off" genetic activity, leading to the identification of an extra 350 disease-specific processes that acted as a "type of on-off switch mechanism".
"This is important ... because the way in which you would develop a therapy or treatment to target these is going to be different if the switch is an on-off switch compared to a dimmer switch," Powell said.
Hope Tanudisastro, a junior medical officer and postdoctoral researcher at Garvan's Centre for Population Genomics and Murdoch Children's Research Institute, said the research also examined DNA "junk".
"A common theme in science is that we always have to challenge assumptions. We always have to look in places that have been understudied or overlooked," she said.
The team analysed DNA stutters, which are tandem repeats within a person's DNA.
While "long written off as junk", stutters could explain how someone's "immune system might be working", Tanudisastro said.
"Yet for years, most genetic studies have set [stutters] aside, and that's partly because they're very hard to read. It's like trying to count identical beads on a string where you can only see a few at a time. At some point, you lose track," she said.
The team measured repeats across the whole genome and tracked their effects in more than five million individual immune cells.
They found more than 69,000 of the repeat switches influencing the activity of genes in the immune system.
Tanudisastro said the research identified how changes in DNA and gene activity within "specific immune cell subtypes" can signal when disease is active.
They could now form the "building blocks" for the development of future targeted drug treatments, she said.
The study identified DNA repeats in "more than 200 genes" linked to conditions such as asthma, Crohn's disease, breast and prostate cancer, high cholesterol, and anaemia.
"These are common chronic conditions, and as our population ages, more Australians will be diagnosed with them, which means that better and more targeted therapies are all the more urgent to be discovered," she said.
Powell said the research is just the start, with further studies planned to examine more diseases.
He said the team will seek to develop "approaches for precision medicine".
"There's this well-recognised huge gap in developing new therapies for conditions that don't have active treatments, and for patients where there are treatments that just don't work," he said.
He said the "map" this research has created could help develop new treatments and identify existing treatments for a range of diseases.
"The findings could help researchers identify new targets for drugs and eventually develop treatments better suited to individual patients."
