From Nobel Intent comes news of a discovery in the Mendelian genetics of Mirror Movements, a condition that causes people to involuntarily move both sides of their body when they intended to only move one.
Aside from being medically relevant, interesting on a population genetics level, and involved an Iranian family, it also caught my eye because about 3 weeks ago we covered the implications of DCC (deleted in colon cancer gene, I know — very clever!) mutations in my pathology course. DCC mutations are found in the sequence of events that lead up to a special type of familial adenomatous polyposis (FAP), known as Gardner syndromes. These colon cancers occurs primarily on the left or descending colon. The morphology of FAP cancers lead to a napkin ring like constriction of the colon that present as alternating bouts of diarrhea and constipation. What makes them unique from other FAPs is that they have present with extracolonic manifestation, like bone cancers.
The DCC gene is on the long arm of chromosome 18. I know that it is a cell surface protein responsible for cell-to-cell and cell-to-matrix adhesion. Normally when cells proliferate, they squeeze up on each other and DCC works via contact inhibition to signal a stop in proliferation because conditions are getting too cramped. Therefore, if DCC is deleted, contact inhibition is lost and cell loses ability to proliferate, yielding a dysplastic growth.
Genbank classifies this gene as one that encodes for a netrin 1 receptor, which I did not know before I read this post. I find this really interesting in the relevance of DCC to Mirror Movements. Dr. John Nicholls,of SISSA in Trieste, Italy, the dude for neurodevelopment, guest lectured my neuroscience course during my second term of medical school last year. I remember him describing netrins as a class of axon guiding proteins that functioned during growth and development. The hallmark experiment I remember him citing was the Oster, et al., 2004, where ganglion cell axon pathfinding in the retina and optic nerve was guided by netrin signals.
It seems that in Mirror Movements, the mutation in DCC prevents it from helping,
“nerve cells on one side of the spinal cord to stay on that side as they extend processes up and down the developing spine…. Because the protein is malformed, the body develops neural connections that route one-sided connections to both sides, producing the mirrored activity.”
I don’t have access to Science unfortunately to research the demographics of the particular SNP they discovered… So I can’t tell you of the gene frequencies… But if anyone does have access to the paper, and doesn’t emailing me, I’ll be very grateful. I love these sorts of discoveries where I learn something new and integrate what I’ve learned the past year and half of medical school!
- Srour M, Rivière JB, Pham JM, Dubé MP, Girard S, Morin S, Dion PA, Asselin G, Rochefort D, Hince P, Diab S, Sharafaddinzadeh N, Chouinard S, Théoret H, Charron F, & Rouleau GA (2010). Mutations in DCC cause congenital mirror movements. Science (New York, N.Y.), 328 (5978) PMID: 20431009