UK Biobank is a major resource for health researchers around the world. UK Biobank collects and stores health, genetic and lifestyle data on 500,000 participants, with the goal of finding treatments and cures for age-related diseases such as Alzheimer’s, cancer and heart disease. All biobank data is de-identified to protect the privacy of participants. UK Biobank was established by the British Department of Health, the Scottish Government, the Wellcome Trust and the Medical Research Council (MRC).
This is a longitudinal study, so UK Biobank will continue to follow the health and medical care of participants and is issuing a program of online questionnaires. Biochemical and genetic analyses are being performed on biological samples collected from participants. Biomedical researchers can apply for access to use UK Biobank data. However, the results of any studies using this data must be shared with the UK Biobank.
UK Biobank Has Genotyped 500,000 Samples
As part of the UK Biobank project, scientists extracted and genotyped DNA from participant blood samples. With 500,000 participants, this was a large-scale undertaking. Therefore, the scientists developed a high-throughput automated DNA extraction method using magnetic beads (Maxwell® 16 Blood DNA Purification Kit, Promega) . In this method, DNA was isolated and washed by applying magnetic force to move the sample between wells containing different buffers.
DNA extraction took place at the UK Biobank. Extracted DNA was then divided into three aliquots: primary storage sample at UK Biobank; backup storage sample at UK Biobank and genotyping sample which was sent to Affymetrix in Santa Clara, USA for genotyping by microarray (UK Biobank Axiom® array and the Affymetrix UK BiLEVE Axiom® Array). Comprehensive information about the SNPs contained on these microarrays can be found on the UK Biobank website. All samples were shipped on dry ice.
UK Biobank Compares DNA Quantification Methods
As with all biobanking methods, the scientists wanted to make sure their extraction protocol resulted in high quality DNA samples. Therefore, prior to genotyping the extracted DNA, they quality controlled their DNA quantification methods and DNA quality by measuring DNA concentration both in-house at the UK Biobank and at an external Affymetrix lab. This is one of the largest, if not the largest, sample size used to be directly compare two DNA quantification methods.
Scientists at UK Biobank quantified DNA concentration using ultraviolet-visible spectroscopy (UV/Vis) measured on the Trinean DropSense™ 96 droplet reader. Affymetrix used a different method employing the fluorescent dye PicoGreen® to quantify DNA. Measurements at UK Biobank showed an average DNA concentration of 38.13ng/μL (with a range from 0.02 to 634.99ng/μL) and an average 260/280 of 1.91. Measurements at Affymetrix showed very similar results, with an average DNA concentration of 37.13ng/μL (0.01 to 730ng/μL) and a 260/280 of 1.93.
84.3% of the samples were of sufficient quality to be genotyped i.e. had DNA concentrations over 10ng/μL and 260/280 over 1.8. This meant 484,325 samples were genotyped by Affymetrix. Genotyping yielded high quality data with an average call rate of 99.48% and pass rate of 99.45%.
The authors concluded that, since both DNA quantification methods gave similar results, perhaps future studies could remove one quantification step so that the DNA is only quantified once before being analyzed. While removing a quantification step can save biobanks time and money, quality assurance and quality control are essential to maintaining high sample quality. Biobanks should periodically validate all equipment, methods and protocols. This is required for regulatory compliance and accreditation by national and international accreditation bodies.
- Welsh, S., et al., Comparison of DNA quantification methodology used in the DNA extraction protocol for the UK Biobank cohort. BMC Genomics, 2017. 18(1): p. 26.