Two groups independently report that the region on 8q24 associated with colorectal cancer risk functions as an enhancer. Lauri Aaltonen and colleagues show that the risk allele at this locus binds with higher affinity to the Wnt-regulated transcription factor TCF4 (also called TCF7L2), conferring enhanced responsiveness to Wnt signaling. Matthew Freedman and colleagues show that the region undergoes long-range interactions with MYC and alleles at the risk-associated SNP bind differentially to TCF7L2.

Thomas Carroll and colleagues show that attenuation of Wnt9b signaling during kidney morphogenesis affects planar cell polarity and causes an increase in tubule diameter. Their analyses suggest that tubule diameter is established by convergent extension movements and subsequently maintained by polarized cell divisions.

Two independent groups identify genetic mutations that cause encephalopathy phenotypes. Yanick Crow and colleagues identify mutations in an interferon-inducible nuclear gene encoding SAMHD1 in individuals with Aicardi-Goutières syndrome, and Jutta Gartner and colleagues identify mutant alleles in the RNASET2 gene that are responsible for the CMV infection–like neurological disorder cystic leukoencephalopathy without megalencephaly (CLM).