A British-Pakistani or British-Bangladeshi person whose parents are cousins may carry two copies of a gene variant that completely switches off a particular gene—and researchers plan to study thousands of such individuals to learn what happens when a human gene is missing entirely. This matters because most genetic studies focus on people whose parents are unrelated, who carry only one copy of a partial gene-disabling variant. Finding people with two copies—natural gene knockouts—lets scientists see the full effect of losing a gene’s function. The team will recruit up to 25,000 apparently healthy volunteers from East London communities where cousin marriage is common, then invite those with promising knockouts for detailed medical tests: blood samples, skin biopsies, exercise blood pressure measurements, body composition scans, and MRI brain and body imaging. If successful, this work could reveal which genes are essential for health and which can be safely disabled—information that directly guides drug development. A gene that can be knocked out without harm in a healthy person becomes a potential target for a drug that mimics that knockout to treat disease. The project also builds a dedicated clinical research facility in Whitechapel, designed to engage local communities and coordinate specialist assessments with other UK and international centres.
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To improve health care, efforts are increasingly focused upon early diagnosis, approaches to disease prevention and the more effective use of available or emerging treatments. Sequencing of the genetic material (genome) is making a powerful contribution to this strategy. The information provided by this methodology seeks to identify individuals at greatest risk for disease, those most likely to benefit from particular interventions and to verify whether new therapies are hitting the key disease target. We plan to accelerate the use of genetics in medicine, through the study of genome in cases of parental relatedness (e.g. cousin marriage), which is common in certain UK ethnic groups including the health disadvantaged British-Bangladeshi and British-Pakistani communities. Recent sequencing 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 have commenced a large-scale community based programme studying as many as 25,000 apparently healthy individuals. Of these, individuals found to possess natural gene inactivating variants considered to be of biomedical importance, will be invited for detailed medical assessment. This may include blood or skin biopsy samples; resting and exercise blood pressure and heart rate measurements; quantification of body composition and brain and body imaging, such as MRI scans. These studies will require the development of a purpose constructed clinical research facility, adjacent to the major hospital at Whitechapel, as the study is founded upon East London (UK) populations. The facility will allow substantial engagement of the local East London communities and enable coordination of more highly specialised assessments, to be undertaken with and through other leading medical research centres across the UK and abroad
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