Clinical application of high throughput molecular screening techniques for pharmacogenomics

Figures & data

Table 1 Comparison of current mutation screening technologies

Technology	Parallel samples	Multiplex markers	Time to results*	Cost per test	Cost of set-up/instrumentation	Offered clinically for pharmacogenomic testing	FDA-cleared or FDA-approved diagnostic devices
Whole genome SNP array	Up to 48	> 900,000 SNPs	1–5 days	High	High	Direct-to-consumer only (Affymetrix SNP Array)	No
Selected marker chip-based microarrays	Up to 8	3–2000	3–6 hours	High	High	Yes	Roche AmpliChip (CYP2D6/CYP2C19); Autogenomics INFINITI (CYP2C19; CYP2C9/VKORC1)
Selected marker bead-based arrays	Up to 48	10–35	4–8 hours	Medium to high	Medium to High	Yes	Luminex xTAG (CYP2D6); Nanosphere Verigene (CYP2C9/VKORC1); GenMark Dx (CYP2C9/VKORC1)
Sanger sequencing	Up to 384, typically < 24	Multiple sequences up to 500–800 bp	2–12 hours	Medium to high	Medium	Yes	Majority LDTs
Pyrosequencing	Up to 96	Multiple sequences up to 300–500 bp	2–6 hours	Medium	Medium to high	Yes	Majority LDTs
Real-time PCR	Up to 384, typically 24 or 96	Up to 16, typically 1–3	1–3 hours	Low to medium	Low to medium	Yes	Some FDA-cleared, many LDTs
High resolution melt curve	Up to 1536, typically 32 or 96	Up to 10, typically 1–3	1–3 hours	Low to medium	Low to medium	Yes	Some FDA-cleared, many LDTs
Single base extension by mass spectrometry (Sequenom)	Up to 384	Up to 1500, typically < 40	10 hours	Low to medium	High	?	No
Isothermal hybridization and cleavage (Invader)	Up to 96	Up to 15, typically 1–2	2–6 hours	Low to medium	Low to medium	Yes	Invader (UGT1A1)
Allele-specific PCR	Approx up to 24	Typically 1	2–6 hours	Low	Low	Yes	Majority LDTs
Restriction fragment length polymorphism	Approx up to 24	Typically 1–2	2–10 hours	Low	Low	Yes	Majority LDTs

Note:

* Time to results does not include nucleic acid extraction (2–12 hours), which is common to all methods above.

Abbreviations: LDT, laboratory-developed test; FDA, Food and Drug Administration; SNP, single nucleotide polymorphism; PCR, polymerase chain reaction; bp, base pair; approx, approximately.