Human genome editing as a tool to establish causality

Abstract

Gentle reader, are you able to drink whole milk? If yes, you have a single base pair in your genome to thank. Certain people can consume milk as adults because of agricultural practice–imposed selection for that ability, which has led to an increase in the frequency of a fascinating allele of the lactase gene. The lactase coding region has remained unchanged, and instead, the enhancer of the gene, which regulates the timing of its expression and lies 14,000 bp upstream of the transcription start site, has acquired a SNP that allows it to be expressed in adults (1). This theme—a variant in a noncoding cis-regulatory region that exerts a major effect on a human—is the focus of an impressive study by Ochiai et al. in PNAS (2). Particularly noteworthy is the use of genome editing with engineered nucleases to establish causality between a noncoding genomic variant and a specific condition.