Jocelyn Krebs got the call every parent dreads. Her son was 19 months old when it came. She had "known for a while that something was up with him," she said. Rhys -- pronounced Reece -- is now 4 years old.
As a molecular biologist at UAA, Krebs studies exactly how a one-cell fertilized egg develops into an incredibly complex adult. She's intimately aware of all the ways this miracle can go awry.
Success requires that biological "traffic signals" turn genes on and off at precise moments in all the right places. An example: DNA has to be able to make heart cells and kidney cells. In a heart cell, you want all the kidney genes turned off.
Figuring out these "traffic signals," or epigenetics, is Krebs' area. When she came to UAA as a young researcher in 2000, this fast-emerging field was seen as the gateway to untangling ailments as different as birth defects and cancer. Discoveries have continued with dramatic speed and results.
But here's the stunner. Krebs' own work on a particular genetic defect called Williams syndrome -- caused by 25 to 30 genes missing on chromosome No. 7 -- turned out to be her son's exact problem. It occurs in 1 of 8,000 births. An egg or sperm can carry the defect.
Williams syndrome affects the brain, which can be up to 25 percent smaller than normal, with some areas overdeveloped and some underdeveloped. Patients also lack a protein that makes blood vessels flexible and can lead to a life-threatening heart condition. High levels of calcium in the blood can lead to seizures. Personality can be affected, leading to extreme friendliness, even toward strangers. The face can appear "pixie-" or "elfin-like." People with the condition may demonstrate remarkable gifts in language and music.
A challenge for researchers is figuring out which missing genes are having which effect.
"I am probably the only person, ever, that when the geneticist called to say, 'It's a deletion on chromosome seven,' knew exactly what that meant. I went, 'Ohhhhh, No, it can't be!' "
The fact that she was even studying Williams syndrome was serendipity. Krebs came to UAA with cancer research in mind: "Like everyone, I have it in my family."
But another UAA researcher happened to have a colony of frogs, and Krebs had a graduate student working with them. That student produced a paper that led Krebs toward a gene called Williams Syndrome Transcription Factor, or WSTF.
To put WSTF's job into context, imagine taking the DNA out of all the cells in your body; end to end, it would stretch to the sun. To fit that genetic material into each cell, it has to be compacted 100,000 times.
"It gets folded and folded and folded in a very organized way, not like wadding a bunch of spaghetti into a very tight space." Chromatin is the name for this compacted DNA plus the "traffic signals" that are involved with it.
In development, when a body needs access to one of those packed-away genes, a "chromatin remodeler" like WSTF helps make it accessible. Krebs was originally interested in WSTF because of this. But as she investigated the gene further, she came to understand what an interesting disease Williams syndrome is.
"Now," she says, "I could learn how epigenetics controls development by understanding where human development goes awry in Williams syndrome."
Her work with WSTF started about three years before her son was diagnosed.
Krebs has learned a lot. In June, she published a paper linking WSTF to defects in neural crest cells. Neural crest cells are embryonic stem cells that appear very early in development when the embryo is just starting to differentiate into brain and spinal tissue. Instead of developing that way, neural crest cells migrate to different parts of the body.
Some travel to a region that will become the heart and form a part of the aorta. Some become the bone, cartilage and cranial nerves of the face. Others give rise to the thyroid and parathyroid, regulators of calcium levels in the body.
When the neural crest cells don't arrive at their intended destination to do their job, genetic havoc ensues.
African clawed frogs are good models for human genetics because they produce larger eggs and development occurs outside the body. Scientists can stain cells and watch what happens to them.
In her lab, Krebs suppressed WSTF in the frogs by about half, the same level patients with Williams syndrome experience. The neural crest cells died, failing to migrate and build body tissue.
This discovery opens the door to possible treatments. Will the day come when a deficit of WSTF in a developing fetus can be recognized early enough to provide the missing material, rescue the endangered cells and facilitate normal development?
While still a long way off, the possibility motivates Krebs.
Coping with her son's disability was a tough, even for a molecular biologist familiar with genes and their complexities.
"For two years, I kept thinking, 'He'll never do this, he'll never get to do that.' But just this year, I stopped doing that.
"My son loves the outdoors. We take him on little hikes. We joke that he's a little botanist -- he loves looking at leaves and trees."
"My son is doing great."
Kathleen McCoy is an electronic media specialist at UAA, where she highlights campus life through social and online media.