A sizeable fraction of the risk for psychiatric illness can be attributed to the genes that we inherit (Polderman et al, 2015). The challenge of identifying gene variants that influence vulnerability to psychiatric illness, which often operate only after interacting with environmental risk factors, is daunting. Nevertheless, advances in genomics are yielding new insights into these risk-modifying gene variants.

A major breakthrough that will facilitate our understanding in this area is the development of CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) (Cong et al, 2013; Jinek et al, 2013); Heidenreich and Zhang, 2016). CRISPR technology utilizes a bacterial borne RNA-guided DNA nuclease defense mechanism to elicit specific gene mutations. Scientists have exploited the mechanism by which bacteriophages transcribe part of a pathogenic genome into guide RNAs (gRNAs) that, as their name implies, serve to guide the endonuclease, Cas9, to cut the DNA of the invading pathogen. The resulting DNA breaks are repaired by either non-homologous end joining (NHEJ) or homology-directed repair (HDR). The NHEJ pathway efficiently ligates broken ends of DNA strands, but often introduces nucleotide insertions or deletions resulting in frameshift mutations that can disrupt expression of the repaired gene. The less efficient but higher fidelity HDR pathway includes a specific DNA sequence to be inserted at the break site.

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