Pharmacogenomics
Impact of Genomic Variation on Drug Response
The impact of genomic variation on drug response may require investigation in clinical studies. For genomic variation that may affect the PK of a medicinal product, clinical studies should be designed in accordance with the Guideline on the use of pharmacogenetic methodologies in the pharmacokinetic evaluation of medicinal products. Genetic ... Read More
DNA Analytics for Genomic Study
A variety of protocols are available for the extraction of gDNA from different sources. It is important to employ a validated method leading to an isolation of gDNA of highest quality, suitable for the nucleotide variation analysis (single or array-based qPCR or end-point PCR), and for sequencing (Sanger, NGS). It ... Read More
Sample Acquisition and Handling During Genomic Study
Identification of genetic variants demands high quality genomic DNA (gDNA). Pre-analytical variations in (i) sample collection, (ii) stability, (iii) sample labelling, (iv) transport to the site of analysis, (v) tissue/sample processing and (vi) storage, should be minimized throughout the workflow to guarantee the highest possible sample quality (see guideline ICH ... Read More
Specific Issues for HLA Alleles
Idiosyncratic adverse drug reactions (ADRs) include examples of strong associations between genotypes and drug responses. These reactions: It is therefore recommended to collect DNA for later HLA typing in a drug developmental program to identify possible useful predictive HLA biomarkers. A comprehensive database listing ADRs associated with the HLA alleles ... Read More
Phenotype and Genotype Correlations
Genetic variants may influence the function of a gene: The PK-phenotype can also be determined by multiple variations in different alleles, e.g. for medicinal products metabolized by multiple pathways. The detection of specific genetic variants in clinical routine helps to improve efficacy and safety of specific medicinal products in use, ... Read More
Common and Rare Genetic Variants
A genetic variant is defined as an allele carrying variation(s) as compared to the gene reference sequence. The term variant is preferably being used instead of the term mutation, which is reserved for rare variants (<1% frequency). Furthermore, the term polymorphism defined as variations having >1 % frequency in the ... Read More