An assumption fundamental to medical genetics is that the DNA sequence of an allele at a particular locus will (in the vast majority of instances) be faithfully transcribed into RNA and translated into protein. This assumption has been largely accepted in spite of known rates of transcriptional and translational errors as well as special cases of RNA editing, in which enzymes alter the RNA sequence post-transcriptionally in ways that can influence translation. If DNA-RNA-peptide sequence fidelity were reduced to zero, it would not be worth attempting to correlate genotype and phenotype. More fundamentally, traits would not be heritable, thereby abrogating a necessary condition for Darwinian evolution.
Therefore, the recent study by Li et al., in Science (2011) is of substantial interest. The authors document numerous differences (still a minority) between DNA sequences and the putatively corresponding RNA sequences (referred to by the authors as RNA-DNA differenes or RDDs).