Goals and Aims

People in a crowd

Genome Research Limited

Many hundreds of genes involved in the disease process have been identified by human genetics studies. However, the discovery of disease-causing variants has been hampered by the resolution of investigation available. This has meant that identified genes have been restricted to those with strong distinctive effects or those with a weak effect that have a relatively high allele frequency (roughly 5% allele frequency or more). Analysis and research suggests that many more low-frequency variants with a weak effect have yet to be found because they occur at a frequency far below 5%.

Computers analysing DNA sequences

Genome Research Limited

The increasing speed of DNA sequencing and computer processing, coupled with the concomitant fall in cost now allows study to an order of magnitude greater depth than before (down to 0.1% allele frequency). The UK10K project has been created to exploit this opportunity to conduct large-scale genome-wide study of thousands of people's DNA sequences to explore rare variants in different types of disease at this unprecedented level.


Through the genome-wide sequencing of deeply phenotyped cohorts, and exome (protein-coding regions) analysis of selected extreme phenotypes, the UK10K project aims to:

Elucidate singleton variants by maximising variation detected

Human chromosomes under a microscope

Adapted from PLoS, doi: 10.1371/ journal.pbio.0030157

By utilising pre-existing cohorts of related phenotypes, the UK10K project will explore the DNA sequence at an order of magnitude deeper than the 1000 Genomes Project for Europe. By carrying out genome-wide sequencing of 4,000 samples from the TwinsUK and ALSPAC cohorts to 6x sequencing depth, researchers will maximise the amount of variation detected and detect singleton variants.

Directly associate genetic variations to phenotypic traits

Human genome karyotype

Genome Research Limited

Both the TwinsUK and ALSPAC cohorts have been deeply phenotyped, allowing genome-wide comparison of people with shared phenotypic traits. By analysing shared genetic variation within twin pairs, the UK10K project will reveal variations that are linked to disease, and screen out those that are not.

Uncover rare variants contributing to disease

DNA Strand

Genome Research Limited

The UK10K project will sequence 6,000 exomes of extreme phenotypes of specific conditions. This focus will substantially increase the study's power to identify rare variants linked to these diseases. Analysis will begin with identified obesity and neurodevelopmental disorder cohorts, with a further eight disease areas currently being explored.

Assign uncovered variations into genotyped cohort and case/control collections

Human DNA sequence

Kate Whitley, Wellcome Images

The variations discovered through genome-wide sequencing of the TwinsUK and ALSPAC cohorts will provide greatly refined data that will be imputed into genotyped cohorts to increase the power of the UK10K study and other case/control studies that the Wellcome Trust Case Control Consortium (WTCCC) is involved in.

Provide a sequence variation resource for future studies

Paper figures

The sequence data set the UK10K project generates will provide a genotype/phenotype resource that will be an order of magnitude deeper than the genetic-only 1000 Genomes Project data set for Europe. By opening access to this information to all researchers, this resource will empower future human genetic research in the UK and beyond.

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