I probably wasn’t the only person who was roped into a fair share of board games this holiday season. I was reintroduced to the classic whodunnit mystery game Clue by my older son. As were were going around the board taking turns, round after round of process of elimination that began aimlessly and gradually triangulated on the remaining possibilities, I confess my mind began to wonder.
I couldn’t shake the feeling that rare disease research is like a game of Clue — but much harder. Instead of solving a fictitious murder, the goal of Rare Clue is to identify the true mastermind behind a rare disease in a lineup of genetic suspects. This, of course, assumes there’s a lone wolf out there. For rare diseases caused by mutations in a single gene, that simplifying assumption is reasonable, even if it turns out that the biology of the single gene is complex.
But a chromosomal disease is a tangled web of conspiracy: dozens or hundreds of so-called disease driver genes on an affected chromosome, some of which could cause a disease if mutated alone, not to mention the shadowy interactions between genes on 8p and genes on other chromosomes. It wasn’t just Miss Scarlett with a wrench in the ballroom. Or Professor Plum with a lead pipe in the study. It’s as though all the suspects were in cahoots, armed to the teeth with all the weapons, lurking in every room of the house….
