Yesterday's Future Today
In a dramatic illustration of the power of emerging genetic technologies, Yale University researchers have reported making a clinical diagnosis for the first time using comprehensive DNA sequencing of all the protein-coding genes in the genome. The information changed the course of treatment of a baby boy suffering from symptoms of dehydration thousands of miles away in Turkey.The baby boy presented symptoms that suggested he was suffering from a genetic condition affecting the way his kidneys functioned. Researchers extracted DNA from a small blood sample and applied a technique, whole exome sequencing, that analyses the small percentage of the genome that contains exons. Exons are stretches of DNA in genes that code for the sequences of amino acids that make up proteins. In eukaroyotes (basically, any organism with a cell nucleus), exons are separated by long stretches of DNA, introns, that don't code for amino acids in proteins. Genomes also contain huge amounts of so-called junk DNA between functioning genes, as well various other kinds of non-amino acid coding DNA. As a result, the DNA that codes for proteins makes up just 1% of the human genome, so a technique that exclusively reads exons saves a lot of time and money, and can quickly and accurately pinpoint mutations.
To cut a long story short, the researchers found that the mutation wasn't, as first suspected, the one that causes a rare condition known as Bartter syndrome, but affected a gene that regulates uptake of chloride and water by cells lining the gastrointestinal tract. Since most (but not all) genetic diseases are caused by mutations in the exome, this has all kinds of implications for fast, rapid, and accurate diagnosis of many diseases, and could help unravel the kind of complex syndromes that Dr Gregory House deals with on a weekly basis.
I'm especially interested in this not only because it is a very clever and neat technique, but it's also a powerful illustration that the future is a lot closer than we think. Or in this instance, than I thought. One of the characters in The Quiet War used a similar technique to diagnose a problem with a microalgal culture essential for the quickening of a biome. Macy Minnot applied a belt-and-braces approach I assumed would be commonplace in her present, our future: a comprehensive reading not only of the entire genome of the recalcitrant microalgal species, but also of its proteome (the complete array of structural and functional proteins in a cell). A little crude compared to the finer focus of exome sequencing, maybe, but able to capture a holistic snapshot of everything going on inside a cell, including all kinds of regulatory functions coded in non-exomic DNA. And by a funny little coincidence pinpointing a problem with another kind of transport gene, this one regulating uptake of phosphate.