Genetic risk: examining immune cells one at a time
· BehindLines newsroom
Why does a difference in DNA raise the risk of disease? According to the Garvan Institute, three papers published in Nature on October 28 seek a clearer answer by examining immune cells individually. Australia's TenK10K project studies the connections between genetic variation, gene activity and the way these cells work.
Several views of the same genome
In an account distributed by Medical Xpress, Garvan describes an initial phase involving nearly 2,000 Australians and more than five million immune cells to measure gene activity. The project's target is 10,000 participants.
The three studies examine complementary aspects: the effects of common or rare variants, those of repeated DNA sequences, and chromatin accessibility. The latter concerns how DNA is organized in ways that allow or restrict access to regulatory regions. Garvan's account.
Cell type changes the interpretation
The chromatin paper specifies its own scope. After quality control, its main analysis retains about 3.5 million cell nuclei from 922 donors. The researchers distinguish 28 types of immune cells.
They connect these maps with gene expression data and genetic studies covering 16 diseases and 44 blood traits. A region associated with risk can therefore be examined in the cell type where its effect appears, rather than in a blood sample treated as one uniform whole. Open-access study.
Leads that still need testing
This mapping offers possible mechanisms to investigate. An association between a variant, a regulatory region and a risk does not, by itself, establish that a medicine works.
Garvan plans, among other things, to expand participants' genetic diversity. This is a practical limitation when interpreting the findings: a map's relevance also depends on the populations studied. The immediate value is to better guide biological research. Therapeutic use would require further validation.