Researchers at the Stanford University School of Medicine say that scientists looking for genetic variants responsible for triggering early-onset diabetes, also known as type-1 diabetes, may be looking in the wrong place.
The researchers say that type-1 diabetes is an autoimmune disease, which is caused when the immune system attacks and destroys insulin-producing cells in a person's pancreas.
In a research paper, published in the journal Clinical Immunology, the researchers say that what triggers such an immune response apparently has less to do with having a distinct set of gene variants than how the behaviour of genes may differ in people with the disease.
Fathman, however, insists that all such researchers may be on the wrong track.
"Take a pair of identical twins, with one having type-1 diabetes. Although both have precisely the same genes, roughly half the time the other twin doesn't get the disease," he says.
In their study, Fathman and his colleagues looked for genes in the diabetic twin that acted differently from the same genes in the other twin who did not have the disease, instead of searching for a faulty gene.
For the purpose, the researchers used two types of bioengineered mice that shared a common genome, with just one key difference.
Fathman revealed the non-obese diabetic (NOD) mice used in the study were extremely likely to get type-1 diabetes, and had an immune-related gene variant closely resembling the one predisposing humans to the disease.
He also revealed that the other strain of mice, known as NOD.B10, had had its chromosomal segment containing the troublesome gene variant replaced with another, harmless version. Such mice never get type-1 diabetes, according to him.
Comparing the activity level of each of the NOD mouse's genes with that of its counterpart in the NOD.B10 animals, the researchers observed that most genes in any given tissue of the diabetes-prone NOD mice showed about the same activity levels as their disease-free NOD.B10 counterparts.
But in each tissue the scientists monitored, certain clusters of genes in NOD-mice seemed to participate in coordinated zigzags of swooping and soaring expression over time, when compared with their healthy NOD-B10 "twins."
Such patterns varied from one tissue to the next and from time to time, but in any given tissue at any given time, they were remarkably consistent.
The researchers said that such time-dependent gene-expression "signatures" could be observed in the NOD mice's peripheral blood, for example, well before the mice began to show characteristic signs of diabetes such as hyperglycemia.
Fathman said that his team's work indicated an exquisite similarity to the gene-expression signatures found in the blood of humans with type-1 diabetes well before the onset of symptoms, providing an early warning for pre-diabetics.
"We need to know that people are on their way to diabetes before they get hyperglycemic or, better, even before their insulin-producing pancreas cells have taken a hit," he said.
He also said that the newly identified genes in the clusters with orchestrated, disease-associated activity changes might point the way to new therapies.
Fathman said that the one thing that still remained unsolved was exactly why a diabetic identical twin's genes began acting differently from the non-diabetic twin's in the first place.
His group is focused on unraveling this mystery.