There is not (yet) a huge catalogue of mutations in ncRNAs that have been shown to affect phenotype, compared to those in protein-coding sequences. However, on the assumption that most ncRNAs are regulatory and that most regulatory regions have yet to be assigned genetic signatures, it is no surprise that this may be the case. On the other hand, as screening for variations affecting complex traits becomes more sophisticated, it is reasonable to anticipate that many will map to, and affect the function of, ncRNAs. Certainly this possibility should be borne in mind in the interpretation of such variations and the consequent studies to define their mechanism of action. The functional analysis of ncRNAs is in its infancy, but in situ hybridization, genomic, and structural characteristics, and the perturbation of their expression by overexpression and siRNA-mediated knockdown are emerging as major tools (Tables 1 and 2). There seems little doubt that there is a hidden world of regulatory architecture underpinning the development of complex organisms that we have yet to explore, both genetically and functionally.
