The human brain develops and modulates more than a trillion connections in ways that depend fundamentally on ligand recognition mediated by cell adhesion molecules (CAMs). These cell surface proteins display single transmembrane, GPI-anchored and other configurations (Li et al, 2009). Products of at least 500 human CAM genes transduce information about ligands expressed by neighboring cells and extracellular matrix, altering cellular signaling and morphology. Understanding the CAM language for establishing and shaping brain connections is key to understanding the connectome.

Common variants in CAM genes have been associated with many human brain and neuropsychiatric disease phenotypes, largely based on modest contributions of multiple genomic variations within each of these genes. Such genetic architecture is unsatisfying for efforts to establish statistically ironclad associations, but is consistent with the likely importance of and selective pressure on the roles that CAMs play. Addiction, abilities to quit smoking, schizophrenia, autism, ADHD, RLS/Willis Ekbom syndrome, cerebral cortical volume and memory provide a sampling of phenotypes associated with variation in CAM genes (Schormair et al, 2008; Uhl et al, 2008). Decoding the language of CAMs is thus also essential to understanding many brain disorders and phenotypes.

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