A new technology for studying the human body’s vast system for toggling genes on and off reveals that genes associated with the immune system toggle more frequently, and those same genes operate differently in women and men.

Some genes are virtually always on, like the clock light on a microwave; others sit unused for years at a time, like some regrettable appliance you bought, stuffed into the back of the closet and forgotten. Some genes can be always on in one person and always off in another. A minority of genes switch on and off, like a favorite cell phone app. A new technology, which makes it possible to study the molecules that regulate all of that switching in living people as they go about their lives, has revealed some intriguing surprises, according to a study from the Stanford University School of Medicine.

One of those discoveries is that the genes that switch on and off differently from person to person are more likely to be associated with autoimmune diseases. Another is that women and men use different switches to turn on many immune system genes. It’s too soon to be sure, but that difference in activity might explain the much higher incidence in women of autoimmune diseases such as scleroderma, lupus and rheumatoid arthritis.

“Part of why this is possible is a new technology that was invented at Stanford for measuring the accessibility of the genome to regulatory elements,” explained the study’s senior author, Howard Chang, MD, PhD, professor of dermatology.

The new technique, called ATAC-seq and developed by Chang’s team, lets researchers sample living cells in real time to see what they are up to. “In the past,” he said, “people needed a huge number of cells to do this kind of measurement. You’d actually need a pound of flesh to get certain rare cell types. So you can’t get that out of a live person — and certainly not more than once, right?”

Examining the source

Researchers coped by growing cells in the lab so they had enough cells to study. “But now,” continued Chang, “you are studying copies of copies; you aren’t studying the original cells anymore. Those months of being grown in the lab completely changes how the cells are behaving and so you are no longer looking at the personal. How the laboratory cells behave has nothing to do with what the person just ate, whether they had a fight with their girlfriend or whether they had an infection,” said Chang. With lab-grown cells, the cells haven’t experienced any of those things, all of which can alter the regulation of individual genes.