There has also been a strong expectation that mutations that have phenotypic effects will map to protein-coding genes or cis-regulatory elements that interact with regulatory proteins. The former has influenced the practical strategies for mutation searching, in terms of a focus on exon scanning of candidate genes (see below), and the latter has influenced the interpretation of regulatory variations, although in only a few cases has the mechanistic basis been determined [71],[145]. Some mutations map to gene “deserts” (see, e.g., [146]), and while it is conceivable that they affect distal enhancers (see, e.g., [147]), it is interesting and relevant to note that there is good evidence that enhancers and other regulatory sequences are transcribed into ncRNAs in the cells in which they are active [45], [83]–[86], and hence may act in part via ncRNAs.
