Dietary effects on the sperm epigenome

饮食对精子表观基因组的影响

• 批准号: 8630339
• 负责人: OLIVER J RANDO
• 金额: $ 65.11万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-14 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8630339
• 关键词: Affect; Animals; Caloric Restriction; Cataloging; Catalogs; Characteristics; Child; Cholesterol Homeostasis; Chromatin; Chromatin Structure; Communities; Control Animal; Cytosine; DNA Sequence; Data; Data Set; Development; Diabetes Mellitus; Diet; Embryo; Embryonic Development; Environment; Epidemiologic Studies; Epidemiology; Epigenetic Process; Evolution; Exhibits; Fatty acid glycerol esters; Fertilization; Fertilization in Vitro; Foundations; Future; Future Generations; Generations; Genetic; Genomics; Grant; Histones; Human; Inbreeding; Individual; Inherited; Life; Link; Mammals; Maps; Measurement; Metabolic; Metabolic Control; Metabolic Diseases; Methylation; Mus; Nutritional status; Parents; Pattern; Phenotype; Plastics; Population; Protein-Restricted Diet; RNA; RNA methylation; Reproduction; Rodent; Sampling; Series; Technology; Time; Variant; Work; base; cardiovascular disorder risk; deep sequencing; epigenome; epigenomics; genetic pedigree; genome analysis; human disease; imprint; innovation; interest; male; offspring; public health relevance; research study; sperm cell; trait

Project Summary/Abstract The inheritance of traits from parent to offspring is a universal characteristic of life on earth, and has fundamental consequences for its inner workings, and for evolution. Recent results in the field of epigenetics have resurrected the once-discredited possibility that the environment of parents could have an effect on the phenotype of their offspring. Inheritance of acquired characters (ie passage of environmental information from one generation to the next) is often called "Lamarckian" inheritance, and demonstration of its existence would drastically alter how we think about evolution, and how human epidemiological studies are carried out. I have used a microarray approach to identify transgenerational effects of the paternal environment on offspring phenotype in mice, linking paternal low protein diet to cholesterol metabolism in offspring. Furthermore, we have shown that this information is carried in sperm. In this project I propose to systematically characterize the mechanism by which environmentally-directed traits are inherited in mice. We will carry out whole-genome analysis of epigenetic information carriers in sperm, thereby identifying diet-directed changes in the sperm epigenome. In addition, using an innovative approach based on in vitro fertilization, we will systematically identify epigenetic marks that persist after fertilization. These studies will have a revolutionary impact on fields ranging from evolution to epidemiology.

项目概要/摘要 从父母到后代的特征遗传是生命体的普遍特征 地球，并对其内部运作和进化产生根本性影响。 表观遗传学领域的最新成果使曾经声名狼藉的理论复活了 父母的环境可能会影响他们的表型 后代。获得的字符的继承（即环境信息的传递） 从一代到下一代）通常被称为“拉马克”继承，并且 证明它的存在将极大地改变我们对进化的看法，并且 如何进行人类流行病学研究。我使用了微阵列方法 确定父本环境对后代表型的跨代影响 在小鼠中，将父亲的低蛋白饮食与后代的胆固醇代谢联系起来。 此外，我们已经证明这些信息是在精子中携带的。 在这个项目中，我建议系统地描述这一机制 环境导向的特征在小鼠中是遗传的。我们将进行全基因组 分析精子中的表观遗传信息载体，从而识别饮食导向 精子表观基因组的变化。此外，使用基于in的创新方法 体外受精后，我们将系统地识别在体外受精后持续存在的表观遗传标记 施肥。这些研究将对以下领域产生革命性影响： 进化到流行病学。