The identification of the sequence changes that directly underpin quantitative trait variations has thus far been possible, or at least achieved, only in well-structured pedigrees in plants and animals. In the few cases where such quantitative trait loci (QTLs) have been mapped to completion, most have been found to be located in noncoding sequences, specifically: (i) regulatory sequences in promoters and distal enhancers (e.g., the “teosinte branched1” mutation affecting branching and inflorescence in maize [114]); (ii) 3′ untranslated regions (UTRs) (e.g., those underlying Tourette's syndrome [115], and muscular hypertrophy in sheep [116]; see also below); (iii) introns (e.g., a QTL affecting muscle growth in domestic pigs [117]); or (iv) intergenic sequences of unknown transcriptional status (e.g., the “callipyge” mutation causing posterior muscular hypertrophy in sheep [118]). The latter occurs in an imprinted locus and affects the expression of a number of protein-coding and ncRNA genes [119] associated with an unusual genetic phenomena termed “polar overdominance” [120], which may also occur in humans [121]. While these mutations are reasonably assumed to be regulatory in nature, their mechanistic basis has not been
