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

地位的继承：重要的不仅仅是你是谁，还有你在哪里

• 批准号: 8550123
• 负责人: CHAO-TING WU
• 金额: $ 82.21万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8550123
• 关键词: Accounting; Affect; Behavior; Biological Assay; Cell Nucleus; Chromosome Positioning; Chromosomes; DNA Sequence Rearrangement; Disease; Epigenetic Process; Fluorescent in Situ Hybridization; Gene Expression; Gene Silencing; Genes; Health; Heritability; Human; Human Development; In Situ Hybridization; Individual; Inheritance Patterns; Location; Peripheral; Positioning Attribute; Process; Regulator Genes; Resolution; abstracting; cost; design; high throughput technology; improved; innovation; new technology; trait

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

描述 摘要： 长期目标：拟议中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：缺失的遗传力，获得的特征和跨代遗传。它代表了一个重大偏离的问题，通常提出的关于染色体定位，但可以证明我们目前所知道的遗传，表观遗传学，以及巨大的能力，染色体定位影响基因表达和染色体行为。这些研究将使用两种新技术：高通量荧光原位杂交（FISH）和Oligopaints，这两种技术旨在降低FISH的成本，同时提高分辨率。 健康相关性：染色体定位是基因表达的有效调节因子;染色体区域的邻近可以指导染色体重排，基因在核的中心或周边部分的位置与不同水平的基因表达相关，并且染色体区域的对位可以激活和沉默基因。由于这些过程对人类正常发育至关重要，因此本文提出的染色体定位研究将与人类健康直接相关。此外，染色体定位可能解释一些令人困惑的遗传性形式的潜力，为这项研究带来了额外的潜力，有助于我们理解疾病，因此，设计 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解释一些令人困惑的遗传形式。它还介绍了两种使用荧光原位杂交（FISH）的新技术，适用于分析多种类型的染色体定位。第一种是高通量FISH技术，允许单个个体每天处理多达3，000次FISH检测，另一种称为Oligopaints，是一种新型探针，