Actress Glenn Close joins the ranks of the genomed; Daniel MacArthur discusses the celebrity genomics trend.
He covers in greater detail the James Lupski genome story, in which the geneticist sequences his own genome to find out what causes his own genetic disorder, Charcot-Marie-Tooth disease. Beside that success story, he places a second study this week that had a lot more trouble – a case in which complete genome sequencing of four members of a family could not by itself find the causative variant for two siblings’ Miller syndrome.
The basic problem here is that we're still extremely bad at differentiating between mutations causing serious disease and perfectly benign polymorphisms - each of us have genomes littered with genetic variants that look like nasty mutations but have little or no effect on health. In fact, Lupski's genome illustrates this nicely: one of the mutations causing his disease is a premature stop codon that disrupts the function of a gene - but his genome also contains an additional 120 stop codons disrupting other genes, presumably without severe health effects.
So all of us are walking around with hundreds of gene-disrupting variants, and finding the single causative gene amongst all that noise is seriously challenging.
We’ve been talking about stop codons and pseudogenes a lot here in the Hawks lab this week.