Phenotyping and Experimental Medicine Centre for naturally occurring Gene Knock-Outs in Humans

为了改善保健，人们越来越多地把工作重点放在早期诊断、疾病预防方法和更有效地利用现有或新出现的治疗方法上。遗传物质（基因组）的测序正在为这一战略做出巨大贡献。该方法提供的信息旨在确定最有可能从特定干预措施中受益的疾病风险最大的个人，并验证新疗法是否达到关键疾病目标。我们计划加快遗传学在医学中的应用，通过研究父母相关性（例如表亲婚姻）的基因组，这在某些英国种族群体中很常见，包括健康状况不佳的英国-孟加拉国和英国-巴基斯坦社区。最近的测序研究表明，父母不相关的人类携带（大多数是单拷贝）约100种遗传变异，这些变异部分关闭了人类基因组中的选定基因。在具有亲本相关性的个体中，这些变异中的一些将在基因组的两个拷贝上被看到，因此某些基因将被完全失活。发现这种遗传变异并研究其后果和益处，既可以增加对人类基因如何工作的了解，也可以增进对遗传变异在相关社区中的健康后果的了解。我们已经开始了一项大规模的社区方案，研究多达25 000名表面上健康的人。其中，被发现拥有被认为具有生物医学重要性的天然基因失活变异的个人将被邀请进行详细的医学评估。这可能包括血液或皮肤活检样本;静息和运动血压和心率测量;身体成分的量化以及大脑和身体成像，如MRI扫描。这些研究将需要开发一个专用的临床研究机构，毗邻白教堂的主要医院，因为研究是基于东伦敦（英国）人群。该设施将允许当地东伦敦社区的实质性参与，并能够协调更高度专业化的评估，这些评估将与英国和国外的其他领先医学研究中心一起进行

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