Every year millions of babies worldwide are born too early. Arriving at six months instead of nine, these underdeveloped babies are at high risk for infant death syndrome, deadly infections, respiratory complications, blindness, cerebral palsy, and learning and developmental disabilities. Two companies – one with the brains, the other with the brawn – are partnering to fight preterm delivery by sequencing the genomes of 500 babies and their parents. They hope to discover new gene targets by examining 1,500 total genomes.
The ambitious collaboration is an indication of how far DNA sequencing and analysis technology has come. Personal genetics companies such as 23andMe limit their analysis to single nucleotide polymorphisms (SNPs). But Complete Genomics is no do-it-yourself DNA analysis kit company. To sequence 1,500 entire genomes – not just SNPs – in an economically feasible manner requires a company with vast resources.
Inova Health System is a not-for-profit healthcare system in Virginia. Their numerous hospitals and other health service entities work together to find ways for improving patient care, education and research. Part of this mission is Inova’s Translational Medicine Institute, established recently in 2010, that focuses on turning the latest genomics research findings into everyday patient care. Complete Genomics, headquartered in Googletown Mountain View, California, is a company that has developed its own technology for sequencing DNA. Inova will collect the samples and outsource the sequencing to Complete Genomics.
The overall project goal is to identify genes that will help to diagnose preterm delivery as well as treat it. It’s also possible that they’ll find gene targets that are important in other obstetrics related abnormalities.
Why a baby is born before its time (before 37 weeks) is a complicated question. To answer it we first have to identify the causal factors. So far the list includes: medical condition of the mother or fetus, genetic influences, environment, past infertility treatments, and behavioral and socioeconomic factors. Reading this rather vague list of factors one gets the sense that researchers have their work cut out for them. Thirty percent of preterm births are attributed to the premature rupture of the amniotic sac that surrounds the fetus. Fifteen to 20 percent are intentionally induced. For almost half of all preterm births, however, the causes are unknown.
Attempts to identify genes that affect preterm delivery has pointed researchers to the immune system. During an infection, certain kinds of hormones are released that trigger the inflammatory process the body uses to fight the infection. Those same hormones affect the labor process. When there is an infection in the amniotic fluid the hormones are released by both the mother and the fetus that set in motion the steps leading to labor. In this scenario, preterm delivery actually has some survival value. Triggering an early labor reduces risk of infection to both the mother and the fetus. It’s estimated that 1 in every 3 preterm deliveries are brought on by an amniotic fluid infection. When labor occurs too early, however, it poses great risk to the baby.
The human genome contains over 3 billion base pairs. Three billion times 1,500 is 4.5 quadrillion. And while the sequencing is one enormous job, analyzing the sequences will be another. Complete Genomics has a supercomputer that will perform this monstrous crunching of numbers.
This kind of high-throughput approach is made possible by advances is both DNA sequencing and computer technology. Keith Raffel, Complete’s Chief Commercial Officer, sees the pilot study as ushering in a new era of genetically-tailored, personalized medicine. “The applications for the genomic information we generate are expanding as the price for genomic sequencing tumbles,” he writes in a Complete Genomics’ blog. “Following Moore’s law, processing power has moved from mainframes to personal computers to smart phones. Whole human genome sequencing is moving along an analogous path. The decreasing price of genomic sequencing is extending its use from large-scale studies of cancer and idiopathic conditions at universities and research institutes to medical care of individuals.”
About 5 to 7 percent of total births in developed countries are preterm. In developing countries the proportion is substantially higher. And, over the last 20 years the incidence of preterm deliveries has been on the rise in developed countries like the US and the UK. In 1990, 10.6 percent of babies born in the US were preterm. In 2008 that number rose to 12.3 percent.
Dr. Clifford Reid, chairman, president and CEO of Complete Genomics hopes to curb the trend and help those for which they can’t. He says in a press release, “We view this as an opportunity for our sequencing service to potentially help create new treatment options for some of the smallest and sickest patients in the hospital.”