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: 8710287
• 负责人: CHAO-TING WU
• 金额: $ 84.75万
• 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/8710287
• 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; 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 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.

描述 抽象的： 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、获得性特征和 跨代遗传。它与通常提出的问题有很大不同 关于染色体定位，但可以通过我们目前所了解的知识来证明 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。该研究将使用两项新技术： 荧光原位杂交 (FISH) 和 Oligopaints，旨在降低成本 FISH 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；邻近性 染色体区域可以指导染色体重排，即基因在中央区域的位置 或细胞核的外围部分与不同水平的基因表达相关，并且并置 染色体区域可以激活和沉默基因。由于这些过程对于 正常人类发育，这里提出的关于染色体定位的研究将对 与人类健康的相关性。此外，染色体定位可能解释的潜力 一些令人费解的遗传力形式为这项研究带来了额外的潜力，有助于我们的理解 疾病，从而设计改善健康的策略。 创新点：这个应用提出了一个新概念，染色体定位或许能够 解释一些令人费解的继承形式。它还介绍了两项使用荧光的新技术 原位杂交 (FISH) 适用于多种类型染色体的分析 定位。第一个是高通量 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，可减少 成本并提高了 FISH 的分辨率。