The quest for the $1,000 genome sequence began in December 2001 at the National Human Genome Research Institute’s scientific retreat. That quest appears to have been completed with Illumina’s January announcement of the HiSeqX Ten machine (see “Illumina”). Fifteen years after the first human genome was sequenced at a cost of $2.7 billion, we are at the dawn of a new era in medicine.
Many more genomes will now be sequenced, and they will be sequenced in much more detail. Today, because examining the whole genome has been so costly, most clinical and research labs look only at the exome, the roughly 1.5 percent of the genome associated with known functions. You might say that we are only looking where we understand. The ability to sequence the whole genome affordably will now generate an abundance of data and an opportunity to understand the importance of many more genetic variants. Sequencing the entire genome typically finds hundreds of times as much variation between any two individuals as just sequencing their exomes, most of it in regions of the genome that are poorly understood.
Learning the functions of those regions will help scientists better understand diseases, drug side effects, and the mechanisms by which the genome functions. Early efforts to use whole-genome sequencing in health care have produced promising results. In our clinic at the Medical College of Wisconsin and Children’s Hospital of Wisconsin, we have already used whole-genome sequencing to identify the causative variant, or mutation, in 26 percent of unexplained diseases we have taken on. The national rate of success without sequencing the genome is between 5 and 10 percent.
Being able to routinely use genome-wide sequencing in the clinic should make it possible to treat patients with an eye to their genetic predisposition toward specific diseases and their responsiveness to particular treatments. We already have evidence that this can improve success rates and reduce costs, which should make these technologies appealing to health insurers.
However, we aren’t there yet. More genomic data must be gathered and shared if we are to understand it well enough to affect clinical outcomes on a large scale. We must also remember that a genome sequence is only the first step; it must be followed up with genetic counseling and evidence-based care. Ethics must also be part of the discussion, because decisions about genomic screening affect generations to come. Now that the technology needed to deliver the $1,000 genome has arrived, we must determine the best way to use this information to save lives.
Howard Jacob is director of the Human and Molecular Genetics Center at the Medical College of Wisconsin.