Lamarck Redux: Transgenerational genetic effects on phenotypes and disease

Lamarck Redux：跨代遗传对表型和疾病的影响

• 批准号: 8645834
• 负责人: JOSEPH H. NADEAU
• 金额: $ 69.87万
• 依托单位: PACIFIC NORTHWEST RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8645834
• 关键词: Lamarck; Redux; Transgenerational; genetic; effects

Traditionally genetics has focused on direct associations between genotypes and phenotypes within individuals. This logical focus on principles of Mendelian genetics has led to a revolution in our understanding of fundamental biological processes and disease genetics. However, observations such as 'missing heritability' in genome-wide association studies suggest that our explanations for phenotypic variation and disease risk are incomplete in important ways. In addition, several recent reports of interacting genes in different generations and transgenerational genetic effects strongly suggest that alternative modes of inheritance exist. These reports involve a wide variety of embryonic and adult traits and can lead to dysfunctions and diseases such as embryonic lethality, cancer, obesity and anxiety. Attributing phenotypes to gene action in previous generations is a fundamental and profound observation that suggests that both epigenetic (non-DNA) and genetic (DNA) mechanisms guide inheritance. Our discoveries implicate RNA editing, miRNA biology, translation control as well as perhaps RNA granules in these transgenerational effects. Proposed work will identify the molecular basis for transgenerational effects and characterize the mechanisms for epigenetics across generations. My accomplishments in comparative genomics, the developmental biology of neural tube defects and testicular cancer, the physiological genetics of obesity and metabolic diseases, and the genetic architecture of complex traits demonstrate my ability to identify hard problems and make important contributions in an unusually wide variety of biomedical fields. The proposed work on transgenerational genetic effects represents a new and exciting area of research, partly because it involves questions and technologies that I am eager to learn, but more importantly because the results could revolutionize our understanding of the molecular mechanisms of inheritance as well as assessment of phenotypic variation and disease risk.

传统上，遗传学关注的是基因型和体内表型之间的直接联系