The role of spatial nuclear organisation ingenome function

构成我们人类基因组的DNA的线性序列图是对我们遗传信息的不完整描述。这是因为关于基因组功能和基因调控的信息也是以DNA序列与染色体和细胞核内的蛋白质折叠的方式编码的。我们的工作试图了解基因组的三维折叠，以及这如何控制我们的基因组在正常发育中的功能，以及这可能在疾病中如何受到干扰。一个特别重要的问题是，基因是如何在时间和空间上被我们基因组中被称为增强子的元件控制的，这些增强子可能位于远离它们控制的基因的地方。这是人类遗传学的一个重要领域，因为在一个种群中，个体之间的大多数常见基因变异影响着我们一生患疾病的风险，存在于增强子中。我们工作的一个显著特点是使用目测分析来研究基因组是如何折叠的。为了做到这一点，我们将荧光原位杂交(FISH)和数字显微镜与自动图像分析软件相结合。

The linear sequence map of the DNA that makes up our human genome is an incomplete description of our genetic information. This is because information on genome function and gene regulation is also encoded in the way that the DNA sequence is folded up with proteins within chromosomes and within the cell nucleus. Our work tries to understand the three-dimensional folding of the genome, and how this controls how our genome functions in normal development and how this may be perturbed in disease. A particularly important question is how genes are controlled in time and space by elements in our genome called enhancers that can located far away from the genes that they control. This is an important area of human genetics because most of the common genetic variation between individuals in a population that affects our life-time risk of developing disease, lies in enhancers. A prominent feature of our work is the use of visual assays to investigate how the genome is folded up. To do this we combine fluorescence in situ hybridisation (FISH) and digital microscopy with the use of automated image analysis software.