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: 8351953
• 负责人: CHAO-TING WU
• 金额: $ 84.55万
• 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/8351953
• 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

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