As has been noted with pathological mutations, the vast majority of known functional intronic polymorphisms are located within the extended consensus sequences of exon-intron splice junctions [2]. Some intronic polymorphic variants do not occur within the splice junctions, however, but nevertheless still act so as to change the splicing phenotype as a consequence of their being located within an intron splice enhancer or branchpoint site, or by activating a cryptic splice site [11,12]. This is, from a biological point of view, a more interesting category of intronic SNP to study, since the mechanisms by which these variants exert their effects on the splicing phenotype are often unclear and may be quite subtle. In the pages of this issue, Millar et al.[13] report that a SNP, buried deep within intron 4 of the human growth hormone (GH1) gene, is of direct functional significance by virtue of its influence on the expression of this gene. This polymorphism therefore joins the ranks of the hitherto relatively small number of human intronic SNPs located outwith exon-intron splice junctions that have been shown by various
