Pharmacogenomics: analysing SNPs in the CYP2D6 gene using amino acid properties

Abstract

The CYP2D6 gene is responsible for metabolising a large portion of the commonly prescribed drugs. Because of its importance, various approaches have been taken to analyse CYP2D6 and Single Nucleotide Polymorphisms (SNPs) throughout its sequence. This study introduces a novel method to analyse the effects of SNPs on encoded protein complexes by focusing on the biochemical properties of each non-synonymous substitution using the program TreeSAAP. Our results show four SNPs in CYP2D6 that exhibit radical changes in amino acid properties which may cause a lack of functionality in the CYP2D6 gene and contribute to a person's inability to metabolise specific drugs.

Evolutionary Pressure on Mitochondrial Cytochrome b Is Consistent with a Role of CytbI7T Affecting Longevity during Caloric Restriction

“…As the first step, we modified the use of TreeSAAP, allowing the program to analyze the physiochemical changes produced by a single amino acid substitution [25]. TreeSAAP was thus used to detect the radical physicochemical shifts that are produced by a mutation substituting a threonine for an isoleucine at site 7 in cytb of mitochondrial complex III.…”

Assessing and improving the accuracy of detecting protein adaptation with the TreeSAAP analytical software

“…The use of amino acid properties results in a high degree of resolution that is more sensitive than the dN/dS approach [12], [16], and allows for the detailed diagnosis of individual amino acid changes in the context of the structure and function of proteins [1]. This alternative approach for detecting selection also exhibits great promise as a tool in the area of biomedical research [4], [14], [10].…”