Holy SNP, Batman!

The interaction between genetic variation and environment is widely acknowledged as the underlying explanation for differences in drug response among individuals, as well as the stratifying force behind disease phenotypes. When DNA variation is found to associate with a phenotype, the investigator's first inclination is to try to explain the finding. The SNP(s) identified (or others in LD) are generally thought to cause either a change in amino acid sequence that alters protein structure/function or a change in gene product expression that is due to altered affinity between cis - and trans -acting factors in the promoter. There is currently an underappreciation for the multifarious interactions that exist between SNPs and the cellular machinery and how this may impact drug response and disease genetics. The purpose of this chapter is to dispel the common view that so-called functional SNPs will be recognizable either by their ability to alter the sequences of cis -acting sites or by their ability to change the amino acid sequences of proteins. Other interactions of functional consequence will also be presented for consideration.