Measurement of genetic risk markers

Collection of DNA samples

Our laboratories have well over ten years experience of DNA isolation with various isolation platforms. We have tested and compared various methods of DNA sample collection and found the buccal swab method to outperform other methods, such as for example saliva samples, in terms of the amounts of DNA obtained and the reliability and reproducibility of the DNA sample. Each DNA sample is quality controlled to see if sufficient volume and concentration of DNA has been achieved for genotype analysis.

Accuracy and reproducibility of genotyping platform

deCODE uses several platforms to measure SNP markers. With the Illumina Human 1M Beadchip, that measures over 1 million SNPs, the overall reproducibility of the chip is over 99.95%. However, reproducibility is not sufficient to guarantee correct genotype allele calls. Thus, all SNPs that are used in disease and trait risk modeling are also tested specifically for their accuracy. For this we use two approaches: i) bi-directional Sanger sequencing (the FDA gold standard) and ii) independent SNP genotyping platform, e.g. Nanogen Centaurus or ABI TaqMan.

Proficiency testing

In short, the proficiency testing program is in two phases; in phase one “true genotypes” for the disease portfolio SNPs are generated for ten proficiency testing participants using the Sanger Sequencing method. The “true genotype” information is used to create a reference table for subsequent verification of proficiency testing results. The reference table is kept in access restricted storage, only accessible for comparison. In phase two, which is performed quarterly, half of the testing participants are randomly chosen and asked to create two separate deCODEme accounts and order the deCODEme service. Samples are processed as if from real customer samples and blinded to all personnel except for the Technical Supervisor. Once processed, results are compared for the accounts, for the same individual, and to the true genotype reference table for the disease portfolio SNPs. Evaluation of the consistency in the disease risk and other features of the service are carried out, both at database level and using the participant web-service accounts. All instances of failures/non-conformance are investigated and handled according to a standard operational procedure for incident investigation.