Most changes in our genomes do not really matter. They make us shorter or taller, fairer or darker. But there are a few characters in the genome—a book of six billion letters that make up one’s DNA—which are single handed in their agenda and overwhelming in their impact. “If that character changes then there’s serious disorder,” says Ramesh Hariharan. A computer scientist by training, Hariharan built bioinformatics tools and did analytics on biological data for over a decade. But when his company, Strand Life Sciences, first entered into clinical services three years ago, he was hit by the life-saving decisions his tools had to make. “In the midst of all the computational work, there’s a decision on the patient, staring in your face. We never had that connect before. It was fascinating,” says he.
The book Genomic Quirks, which released in March, is a result of that patient connect. It is about those ‘few’ characters that turn a person’s life topsy-turvy even as doctors scramble to nail the root cause of a disease. And by a ‘few’, Hariharan actually means a few hundred thousand letters, which is still a small fraction of the entire pool of six billion letters.
About one in 100 people is affected by such characters. For some, the impact may be slightly moderate; in others, it’s life changing. Take for instance the story of Mira and Sai, a young couple who lost two sons, both under 18 months, to a mysterious disease the physicians and geneticists couldn’t diagnose.
The boys, Som and Rom, had prominent eyes, small chins and full cheeks. Could there be a clue in those features? Once the genomes of Som and the parents were sequenced, a list of variant characters was ready for investigation. Whittling them down to the organs that were affected—facial structures, lungs (respiratory problems) and so on, the investigators ended up with a few hundred genes, which might hold the secret to the mystery. Narrowing the gaze further, through some thought experiments that took them back 500 million years, they arrived at an errant character. But it was uncharted territory—nowhere in genomics literature had that genetic anomaly been reported. And while Hariharan’s team pored over tonnes of data and scoured the worldwide web of scientific literature, time was running out. The couple was expecting their third child and was desperate to know if the baby would meet the same tragic fate as the two boys.
“In some cases, the defective characters are known to the doctors but in this case, it was an unexpected gene. You had to convince the doctor who herself was not sure and was in a dilemma if she should use our information to take a decision to terminate the pregnancy or not,” says Hariharan, relieved that the doctor relied on their results. “When it comes to patients, you can think of us as a glorified reporting service, which says—here are the things, which indicate we have found the answer; here are the things, which indicate we are in the realm of the unknown.