Table 1

Summary of genetic variations

DNA variations
Single nucleotide polymorphismsChange in nucleotide base as described in text. Does not need to be non-synonymous (leading to an interrupted polypeptide sequence) to be clinically relevant. SNPs in promoter,12 intron,13 spice site14 and intragenic regions have been associated with disease or susceptibility to disease.15 16
Variable number tandem repeatsMicrosatellite: sequence of 2–6 repeating bases
for instance, trinucleotide repeat of Fragile X syndrome.
Minisatellite: sequence repeat of >6 bases.17
Copy number variantsVariations of larger sections of DNA (one kilobase to several megabases), which may be deleted or repeated.18 19
MicroRNAs (MiRNAs)Small, single-stranded, 21–23 nucleotide-long, independent functional units of non-coding RNA.20–22 They contain complementary RNA to bind to target transcript in the 3′ untranslated region, which can inhibit translation decreasing expression and destabilise their target mRNA.18 23 24 MiRNA polymorphisms can affect regulation of a drug target gene, causing drug resistance.23
Epigenetic variation
Histone acetylationWithin the nucleus, DNA is wrapped around proteins, called histones, as chromatin. Histone acetylation creates an accessible chromatin conformation that facilitates transcription.25
DNA methylationDNA methylation reduces transcription by either detrimentally altering the chromatin conformation or by preventing the binding of transcription factor to its DNA binding site.26
Post-translational modification of proteins
Glycosylation, phosphorylation, oxidation, ubiquitination, methylation, etcThe human proteome is estimated to contain between 20 000 and 25 000 non-redundant proteins. This number then increases substantially when post-transcriptional RNA splicing and proteolysis are accounted for. Further post-transcriptional modifications are estimated to bring the total number of unique human proteins >1 million.27 28
  • SNP, single nucleotide polymorphism.