As a toddler, Nicholas Volker failed to gain weight. Doctors at Wisconsin Children’s Hospital discovered his intestines were inflamed and ulcerated. When the boy ate, holes would form in his intestine, spilling the contents into his abdomen. While Nicholas’ symptoms resembled Crohn’s disease, the usual treatments were ineffective. More than 100 surgeries were performed during the next two years, including the removal of his colon. Still, Nicholas’ condition worsened.
The symptoms suggested a possible immune deficiency and a bone marrow transplant was recommended. Its success, however, depended on identifying the specific underlying cause of Nicholas’ symptoms. Consequently, the medical team decided to sequence Nicholas’ DNA. They began by sequencing individual genes that were known candidates for irritable bowel syndrome and Crohn’s disease. No mutations were identified. The search expanded to sequence the exons of all the genes in Nicholas’ genome, a process known as exome sequencing.
Approximately 1 percent of the human genome consists of the genes. Nicholas’ exons were sequenced extensively – an average of 34 times, to reduce the chance that a mutation might be missed. His sequences were compared against reference sequences generated thanks to the Human Genome Project and its follow-on studies. More than 16,000 variations in Nicholas’ DNA recipe were discovered. Many of these differences had no observable effect. Others influenced physical features like his blond hair and hazel eyes.