The inheritance of position: It's not just who you are, it's where you are

描述 摘要： 长期目标：拟议的研究将询问染色体定位是否能告诉我们三种令人困惑的遗传模式：缺失遗传性、获得性特征和跨代遗传。它代表了与通常提出的关于染色体定位的问题的重大背离，但可以根据我们目前所知的遗传、表观遗传学以及染色体定位的巨大能力来影响基因表达和染色体行为。这项研究将使用两项新技术：高通量荧光原位杂交(FISH)和寡画，这两项技术旨在降低鱼类的成本，同时提高分辨率。与健康相关：染色体定位是基因表达的有效调节因素；染色体区域的接近可以指导染色体重排，基因在核中心或外围部分的位置与不同水平的基因表达有关，染色体区域的位置可以激活和沉默基因。由于这些过程对正常的人类发育是必不可少的，这里提出的关于染色体定位的研究将与人类健康直接相关。此外，染色体定位可能解释了一些令人费解的遗传性形式，这为这项研究带来了额外的潜力，有助于我们对疾病的理解，因此，设计 改善健康的战略。创新：这项申请提出了一个新的概念，即染色体定位可能能够解释一些令人费解的遗传形式。它还介绍了两种使用荧光原位杂交(FISH)的新技术，这两种技术适用于多种类型的染色体定位分析。第一种是高通量鱼类技术，允许单个个体每天处理多达3000次鱼类分析；另一种是称为寡配色的新型探测器，它

DESCRIPTION Abstract: Long-term objectives: The proposed studies will ask whether chromosome positioning can inform us about three puzzling patterns of inheritance: missing heritability, acquired traits, and transgenerational inheritance. It represents a major departure from the questions that are usually posed with respect to chromosome positioning, but can be justified by what we currently know about inheritance, epigenetics, and the tremendous capacity of chromosome positioning to affect gene expression and chromosome behavior. The studies will use two new technologies: high-throughput fluorescent in situ hybridization (FISH) and Oligopaints, which have been designed to reduce the cost of FISH while increasing resolution. Health relatedness: Chromosome positioning is a potent regulator of gene expression; proximity of chromosomal regions can direct chromosome rearrangements, the location of genes within the cen- tral or peripheral parts of the nucleus is associated with different levels of gene expression, and ap- position of chromosomal regions can activate and silence genes. As these processes are essential for normal human development, the studies proposed here on chromosome positioning will have direct relevance to human health. In addition, the potential that chromosome positioning may account for some puzzling forms of heritability brings additional potential for this study to contribute to our under- standing of disease and, therefore, the design of strategies to improve health. Innovation: This application proposes a new concept, that chromosome positioning may be able to account for some puzzling forms of inheritance. It also introduces two new technologies using fluo- rescent in situ hybridization (FISH) that are appropriate for the analysis of many types of chromosome positioning. The first is a technology for high-throughput FISH, permitting a single individual to process up to 3,000 FISH assays per day, and the other, called Oligopaints, is a new type of probe th