Even experts struggle to make sense of genomic data, the Nature News Blog reports. An executive at DNA analysis company Golden Helix took advantage of an opportunity offered by 23andMe to have his exome sequenced. Interpretation, however, was not included.
Gabe Rudy, vice president of product development at Golden Helix, hosted a webcast this week, guiding participants through his personal quest at interpreting his exome data.
When 23andMe returned the raw sequence data back to Rudy it contained around 151,000 variants. Using tools developed by his company, as well as publicly available databases of common variants, he was able to narrow that list down 1,700 variants likely to affect the protein. Looking at just the 197 that were predicted to be loss-of-function, he ran those through OMIM, a database of genes associated with disease, and looked only at genes in which both copies contained a variant, shrinking the list to 16.
After examining the biology behind each of the 16, he identified additional likely common variants, errors, and three variants that appeared real and to be located in genes associated with disease.
For two of those, he could not find any information about potential functional consequences, and the third variant is associated with a fatal neonatal disease and a late-onset form implicated with toxic build-up of metabolites in dietary protein.
While a number of academic centers have already implemented exome sequencing to diagnose rare diseases, exome sequencing in presumably healthy individuals is still rare, and Rudy's case demonstrates why. Making sense of variants and discerning real variants from sequence errors without an association with a disease phenotype is extremely difficult.
23andMe is aiming to improve on at least one aspect of this problem. As reported by sister publication GenomeWeb Daily News, the company recently received a grant from the National Institutes of Health to study error rates from sequencing technology and define data quality metrics and technical specifications to support its sequencing-based Personal Genome Service.