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：缺失的遗传性，获得的特征， 跨代遗传它代表了与通常提出的问题的重大偏离 但可以通过我们目前所知道的 遗传，表观遗传学，以及染色体定位影响基因的巨大能力 表达和染色体行为。这些研究将使用两种新技术： 荧光原位杂交（FISH）和寡肽，这是为了降低成本， 提高分辨率的同时进行FISH。 健康相关性：染色体定位是基因表达的有效调节因子; 染色体区域可以指导染色体重排，基因在中央区域的位置， 或细胞核的周边部分与不同水平的基因表达有关， 可以激活和沉默基因。由于这些过程对于 正常人类发育，这里提出的染色体定位研究将有直接的意义。 与人类健康的相关性。此外，染色体定位可能解释了 一些令人困惑的遗传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。 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 来解释一些令人困惑的遗传形式它还介绍了两种新技术， 原位杂交（FISH）适用于分析许多类型的染色体 定位第一种是高通量FISH技术，允许单个个体处理 每天多达3，000次FISH检测，另一种称为Oligopaints，是一种新型探针， 提高了FISH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.