Posted on behalf of Brendan Maher
At the second annual personal genomes meeting at Cold Spring Harbor Laboratory in New York this week, bioentrepreneur Hugh Rienhoff updated conference-goers on his very personal quest to find a molecular diagnosis for his daughter Beatrice (pictured). 
Recently, he’s enlisted the help of second-generation sequencing giant Illumina to sequence all the genes expressed into messenger RNA from his daughter’s white blood cells, as well as that from his wife and himself in hopes that sequencing the three might flush out a genetic defect responsible for the five-year-old’s mysterious constellation of symptoms, which include low muscle mass and mild deformities in the hands and feet. See my 2007 Nature feature here for more details on Rienhoff’s quest.
Because Illumina sequences from mRNA transcripts, Vincent Butty of the Massachusetts Institute of Technology — who’s been analyzing the data — has been able to see direct relationships between the sequence of the genes and their expression levels. For example, he found a variant of CPNE-1 with a single base pair change. Both Rienhoff and his wife have one normal copy of the gene and one copy of the variant, but Beatrice inherited both copies of the variant, and her expression of the gene is drastically reduced compared to her parents. It’s not clear yet if the variant is responsible for her condition, however, and there are many other leads to follow in the data.
Nevertheless, Illumina plans to perform this style of transcriptome profiling on up to nine more family trios, five of whom have children that have been diagnosed with Loyes Dietz syndrome, and four others with a variety of clinical presentations including autism, developmental delays and congenital heart failure.
Gary Schroth, who runs the RNA analysis division at Illumina, says the research could provide proof-of-principle examples for moving transcriptome sequencing into clinical application. The sequences are being provided for the patients and their families for free — a cost of roughly $6,000 per family, he estimates.
It helps to know someone. Rienhoff was able to get Illumina interested based in part on his friendship with Illumina CEO Jay Flatley, and several of the new trios to be sequenced are friends of Rienhoff’s. Still says Schroth, “it’s more than a pet project. It’s a legitimate application for my group to work on.”
For Rienhoff, of course, it’s personal.
Image: C. Pickens