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With Chip Design Finalized, UK Biobank, Affymetrix Commence 500K-Sample Genotyping Effort

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The UK Biobank and Affymetrix recently finished developing an array that will be used to genotype all 500,000 samples in UKBB's biorepository.

Affymetrix is also selling the chip to its customers, and has seen "significant" demand for it, according to company representatives.

Peter Donnelly, a professor of statistical science at the University of Oxford, provided an overview of the UKBB's chip during an Affymetrix workshop held at the American Society of Human Genetics' annual meeting in Boston last week.

Following his presentation, Donnelly told BioArray News that he led a team that selected the content for the array. The group finished the array design in early August, and Affymetrix began running samples on the arrays later that month.

The first 50,000 samples of the large genotyping effort are being run for the purposes of the UK Biobank Lung Exome Variant Evaluation, or BiLEVE project. Funded by the UK Medical Research Council and approved by UKBB, the year-old effort aims to better understand genetic predisposition to lung disease.

Donnelly estimated that the BiLEVE project's samples should be genotyped by the end of the year. Once those samples are genotyped on the new array, Affymetrix will as a service genotype UKBB's remaining 450,000 samples, he said.

According to Donnelly, UKBB expects Affymetrix to process about 6,000 samples per week on its high-throughput and automated Axiom genotyping platform. At that rate, UKBB anticipates that all of its samples will be genotyped by June 2015.

Once array data is achieved for UKBB's samples, it will be made available to investigators who wish to use it, Donnelly said.

"UKBB is first and foremost a resource," said Donnelly. "Researchers can apply to use the data and analyze it," he said. "It is all about constructing a resource for the research community internationally to use."

UK-centric

Initiated in 2005, UKBB has collected blood, urine, and saliva samples, along with detailed information on 500,000 Britons who were between 40 and 69 years old at the time of enrollment. UKBB is considered a national health resource in the UK, and its ultimate aim is to improve the prevention, diagnosis, and treatment of diseases and conditions such as cancer, heart diseases, stroke, diabetes, arthritis, osteoporosis, eye disorders, depression, and forms of dementia. Earlier this year, UKBB announced an agreement with Affymetrix to genotype all of the samples in its database using a custom array design (BAN 3/26/2013).

Donnelly said that because 450,000 of the half million samples in its biorepository were collected from people who designated themselves as White British, the UKBB requested that the array be focused on White British populations in England, Wales, Scotland, and Northern Ireland.

The chip contains approximately 821,000 markers in total. Of these, about 350,000 are SNPs that capture common variants, meaning those that have a minor allele frequency of greater than 5 percent. Another 270,000 SNPs are included to capture low-frequency variants that have an MAF of between 1 and 5 percent. The group also selected content from Affymetrix's exome arrays, as well as from collaborators that it found to be more frequently represented in the UK population.

UKBB's chip also contains more focused content, including variants that have been reported as being associated with certain conditions.

"We wanted to do an experiment where we looked at variants in very large sample sizes to see whether ordinary people carry the same variants without necessarily having severe phenotypes as a consequence," Donnelly said.

He noted that the array also includes 20,000 SNPs that tag haplotypes that are "thought to be inherited from Neanderthal ancestors on the grounds that things that we have inherited from Neanderthals and still have might be enriched for variants that are biologically important."

The chip also contains about 40,000 SNPs contributed from groups studying various diseases; all of the SNPs in the US National Human Genome Institute's GWAS Catalog; and all of the custom neurodegenerative disease-focused SNPs from the NeuroX Chip, an Illumina-manufactured array developed within the Parkinson's Progression Markers Initiative, Donnelly said.

While UKBB's array may seem insular in its focus, some researchers who are not involved in the effort are eager to use it in their studies.

"I would say that demand for that array or derivatives of that array are very significant," said Mike Nemzek, Affymetrix's vice president of strategic marketing for genotyping.

Nemzek told BioArray News at the conference that the array became available for general research shortly after the Santa Clara, Calif.-based company commenced genotyping the UKBB's samples.

He added that researchers are also interested in using UKBB's chip as a template for custom arrays focused on their own populations of interest.

"You can start with the UK Biobank, which has nice attributes but is heavily UK-centric, take out SNPs that are representing the UK population heavily, and replace them with SNPs that represent the population of interest," said Nemzek. "All of these countries want a particular flavor and they can just optimize [this design] to meet their demands."

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