Completed Genetics & Molecular Biology Pregnancy, Children & Inherited Conditions

East London Genes & Health: human knockouts in a population genomic medicine cohort of British-South Asians

Funder Wellcome Charity-funded
Recipient organisation Queen Mary University of London
Funding £4.1M
Period Oct 2018 — Oct 2023

In plain English

AI plain-English summary

East London Genes & Health is recruiting 100,000 British-South Asian volunteers to find people who naturally lack working copies of specific genes—so-called "human knockouts"—and study what happens to their health as a result. This matters because most genetic research has focused on people of European ancestry, missing rare gene variants that are more common in South Asian populations due to higher rates of consanguinity (marriage between relatives). These naturally occurring knockouts offer a unique window into what happens when a gene is completely disabled in a living adult—information that is otherwise only available from lab animals or cell cultures. If successful, the project will create a worldwide database of human knockouts, allowing researchers to link missing genes to disease risk or protection. By sequencing the genomes of consanguineous individuals and analysing their blood chemistry, the team can identify which gene disruptions cause major biological system failures and which are harmless. This could accelerate the discovery of drug targets—if a natural knockout protects against heart disease, for example, a drug that mimics that effect might do the same. The work is primarily fundamental science, but with direct potential to improve medical diagnostics and treatment for populations currently underserved by genomic medicine.

View original technical description
East London Genes & Health is a long term programme for population genomic medicine research in British-South Asian adults. Unique features include high rates of health deprivation, especially diabetes, cardiovascular disease and mental health; high rates of consanguinity (including human knockouts, rare predicted loss of function variants occurring as homozygotes); local excellence in e-health record access/analysis; and recall for further research by genotype/phenotype. In this proposal we wish to continue and expand successful East London Genes & Health recruitment and commence a new site Bradford Genes & Health - to reach 100,000 volunteers; add value to the Genes & Health resource through SNP array genotyping all samples; and by sequencing and analysing consanguineous individuals. This will then enable us as a collaborative team to ask detailed research questions about adult-human knockouts. Specifically we will perform population based analyses of naturally occurring adult-human knockouts to better understand their population genetics, and (with Deciphering Developmental Disorders) recessive disease; contribute to and establish The Human Knockout Project, a worldwide database of population-based studies of human knockouts; perform blood -omics to study major perturbations of biological systems including downstream networks; and deeply study individuals with knockouts and other variants in reported Mendelian disease genes.

View the original record at the funder ↗

Researchers

David van Heel (EPMC Awardee)

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Original classification

Collaborative Award in Science

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