Using new technology, researchers were able to sequence and analyze whole genomes of infants in about 50 hours. While the rapid data is impressive, even more impressive was how they demonstrated the data’s timely value. After sequencing the genomes of seven babies that died near birth, the doctors were able to retrospectively diagnose five of them, demonstrating that the quick turnaround between sequencing and diagnosis has the potential to save many of these fragile lives.
There are more than 3,500 diseases known to be caused by mutations in single genes, and many of these diseases manifest in the first month of life. Because single genes are affected, these monogentic diseases are simple enough to be detected through genetic screening. Using current methods, however, screening newborns typically takes four to six weeks. Not only is this waiting period difficult for the parents, but the delay means that treatment all too often arrives after it’s too late.
In the current study, the researchers used an Illumina HiSeq 2500 to sequence the baby genomes. The 50 hour screening time was not due to sequencing speed, but rather analysis speed. It took about four and a half hours to prepare the samples and another twenty-five and half hours to sequence the genomes with the HiSeq machine. The remaining 20 hours then was all it took to analyze the entire 3.2 billion base pairs of the genomes and pinpoint causal mutations. They were able to achieve such efficiency by modifying their analysis software to be both automated and smart. Much of what is normally performed manually, like finding a mutation and associating it with a disease, was carried out by software. In addition, the clinical features of the babies were taken into account such that the software focused on genes that were most likely linked to the symptoms, greatly decreasing the analysis workload.
And quality was not sacrificed for speed. Retrospectively diagnosing the critical illnesses of five out of seven babies demonstrates that the system could make a huge difference in a clinical setting.
The study, led by Stephen Kingsmore, director of the Center for Pediatric Genomic Medicine, was published recently in Science Translational Medicine.
“Up to one third of babies admitted to a [neonatal intensive care unit] in the U.S. have genetic diseases,” Kingsmore said in a press release. “By obtaining an interpreted genome in about two days, physicians can make practical use of diagnostic results to tailor treatments to individual infants and children.”
There are other benefits to having timely access to newborn genomes. By honing in on the most probable causes of illness, doctors – and parents – can limit the number of tests run, saving on time and cost, and shortening hospitalization stays.
As hinted at by the name of Kingsmore’s center, the era of genetics-based personalized medicine is fast approaching. Right now our understanding of genetic bases for disease remains extremely limited. But as sequencing continues to get cheaper, faster, and more accurate, and analysis software gets more sophisticated, researchers will be perpetually better equipped to meet the challenge of understanding the entire genome.
Sequencing whole genomes, as performed in the current study, is still a rare practice. Most sequencing centers opt for the high percentage game of sequencing the exome, the part of the genome that codes for the body’s main machinery: proteins. But the exome only accounts for one percent of the entire genome. But even if, as we expect, future research does show that the vast majority of diseases are due to mutated genes in the exome, it doesn’t preclude the need to learn as much as we can about the genome as a whole.
Leaders in the genomics field have predicted that the future of genomics-based medicine will begin with ill newborns that doctors are unable to diagnose. The current study convincingly demonstrates the feasibility of making genomic information a routine part of healthcare. Hopefully as technology improves and understanding deepens, we'll begin to measure real results in amount of saved lives.