Allele definition

How to define PGx alleles

PGx alleles are defined as collections of one or more SNPs, INDELs or structural variants. When a patient is sequenced by next generation sequencing (NGS) we may typically observe more variants than those which are included in any individual PGx allele definitions. miniatyr|The 16 possible haplotypes for a four loci, decomposed variant calling This means that

• Patients may have a large, ambiguous number of matching PGx alleles
• Patients may have additional variants that may modify the effect of a known PGx allele

We can illustrate all the possible PGx allele definitions for a four loci PGx haplotype as

The SNP array method

miniatyr|PGx alleles defined as collections of variants, with no requirement on loci that are not part of the definition, will assign the same PGx allele to several different haplotypes This definition only requires matches for variants explicitly included in PGx allele definitions.

This means that

• Several PGx alleles may match to the patient
• But the presence of additional variants will have no effect on reported PGx alleles

The PharmCAT method

This definition require matches also for variants not explicitly included in PGx allele definitions. miniatyr|PGx alleles defined as complete haplotypes classifies the patient uniquely This means that

• Several PGx alleles may not be simultaneously reported for the same patient
• But whenever we have additional variants, no PGx alleles will be reported