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可以 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 代际遗传。它与通常提出的问题有很大的不同 关于染色体定位，但可以用我们目前所知的来证明 遗传、表观遗传学和染色体定位影响基因的巨大能力 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)和寡颜料，旨在降低 在提高分辨率的同时钓鱼。 与健康相关：染色体定位是基因表达的有效调节因素；接近 的染色体区域可以直接进行染色体重排，将基因定位在中央 或核的外围部分与不同水平的基因表达和对位有关 染色体区域的变化可以激活和沉默基因。因为这些过程对于 人类正常发育，这里提出的关于染色体定位的研究将直接 与人类健康相关。此外，染色体定位可能解释了 一些令人费解的遗传性形式为这项研究带来了额外的潜力，有助于我们理解 因此，制定改善健康的战略是必要的。 创新：该应用程序提出了一个新的概念，即染色体定位可能能够 来解释一些令人费解的继承形式。它还介绍了两种使用荧光的新技术 适用于多种类型染色体分析的原位杂交技术 定位。第一种是高通量鱼类技术，允许单个个体加工 每天多达3000次鱼类化验，另一种被称为寡画的新型探测器，可以减少 降低了成本，提高了鱼的分辨率。

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 central or peripheral parts of the nucleus is associated with different levels of gene expression, and apposition 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 understanding 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 fluorescent 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 that reduces the cost and increases the resolution of FISH.