Precisely because we invariably adopt a gene-centric approach to screening introns for functional polymorphisms, we should be wary of the existence of overlapping genes, a not infrequent occurrence in our complex genome. Thus, for example, the functional SNP rs4988235, located 13.9 kilobases upstream of the lactase (LCT) gene and associated with adult-type hypolactasia, actually resides deep within intron 13 of the minichromosome maintenance complex component 6 (MCM6) gene [17-19]. In addition, since disease-associated intronic SNPs that play a role in long-range gene regulation have also recently been identified,[20,21] we should be aware that some SNPs may influence the expression of remote genes at distance, rather than the expression of those genes which actually host them. These caveats notwithstanding, new techniques such as chromosome conformational capture [22] and chromatin immunoprecipitation followed by deep sequencing (ChIP-seq)[23] promise greatly to increase the number of functional intronic polymorphisms identified, thereby potentially pinpointing the locations of a whole new lexicon of intron-located regulatory elements, which will increase our understanding of intron structure and function.
