Researchers at the Medical College of Wisconsin are taking pioneering steps to make whole-genome sequencing a standard part of diagnostic testing for children with rare inherited disorders not easily diagnosed by traditional methods. The technology has come far in the decade since the $3 billion human genome project was published—so far, in fact, that a health insurer has offered to cover the sequencing in cases where it would be cheaper than conventional genetic testing.
Whole-genome sequencing—reading a patient’s entire DNA code—now costs about the same as sequencing just a few genes through commercial diagnostic tests, says Howard Jacob, director of the college’s Human and Molecular Genetics Center.
Over the last year, whole-genome sequencing has proved its medical worth. Scientists have been able to pinpoint the genetic mutations underlying a number of rare, difficult-to-diagnose diseases, in some cases resulting in life-saving treatments. But despite the medical benefits, these efforts have so far been limited to the research realm.
“Howard wants to make this a routine clinical test,” says Nicholas Schork, director of bioinformatics and biostatistics at the Scripps Translational Science Institute. “He has gone the extra mile to convince regulatory and legal people at his institution that this should be part of the diagnostic.”
The Wisconsin team garnered international attention in December when researchers published their effort to diagnose Nicholas Volker, a six-year-old with a severe form of inflammatory bowel disease that failed to respond to treatment. By the age of three, Nicholas had already undergone 100 surgeries to try to repair his damaged digestive system. He also had symptoms of an immune disorder, and physicians were considering a cord-blood transplant—a transfusion of stem cells from umbilical cord blood, similar to a bone-marrow transplant—to reboot his immune system. But without a definitive diagnosis, they were hesitant to undertake this procedure, which carries a significant risk of death.
Jacob took on Nicholas’s case thanks to a desperate letter from his physician. After sequencing the child’s genome, Jacob’s team identified a mutation on the X chromosome that has been linked to an inherited immune disorder. The mutation is unique, not found in any of the other human—or animal—genomes sequenced to date. With the new diagnosis in hand, doctors performed the cord-blood transplant. Eight months later Nicholas is out of the hospital and doing well.
The Volker case was considered a research project. But Jacob felt strongly that genome sequencing should be part of the ordinary diagnostic arsenal for children with rare inherited disorders. He has spent the last year and a half trying to transform what has been a promising medical technology into a routine diagnostic, with standard procedures and clinically certified tests. Five hundred pages of forms later, “we created a separate infrastructure for doing purely clinical cases,” says Jacob, who presented details of his efforts last week at the Future of Genomic Medicine conference in San Diego, California.