British autozygosity population study of natural gene inactivation

Parental relatedness (e.g. cousin marriage) is common in certain UK ethnic groups including the health disadvantaged British-Bangladeshi and British-Pakistani communities. Recent studies show that humans whose parents were unrelated carry (mostly single copies) of ~100 genetic variants that partially switch off selected genes in their human genome. In individuals with parental relatedness, some of these variants will be seen on both copies of the genome and thus certain genes will be completely inactivated. Finding such genetic variants and examining their consequences and benefits can lead both to an increased knowledge of how human genes work and an improved understanding of the health consequences of genetic variation in the relevant communities.

We propose a large-scale community based programme studying 25,000 such individuals (typically, healthy adults). Of these, 3,000 individuals found to possess natural gene inactivating variants of biomedical importance will be brought back for detailed study (e.g. further blood or skin samples; clinical measurements; or an MRI scan). We will focus on East London (UK) populations, and coordinate the study around our Whitechapel site. Alongside scientific studies of gene function, we will substantially engage East London communities and more widely, increasing public engagement around the human genome and wellbeing.