Molecular causes and fitness consequences of complex trait variation

复杂性状变异的分子原因和适应性后果

• 批准号: 7565012
• 负责人: Storrs Thomas Mitchell-Olds
• 金额: $ 29.64万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7565012
• 关键词: Alleles; Biochemistry; Biomedical Research; Characteristics; Cloning; Complex; Environment; Equilibrium; Evolution; Gastritis; Genes; Genetic; Genetic Drift; Genetic Polymorphism; Genetic Variation; Genome; Genomics; Genotype; Glucosinolates; Goals; Helicobacter pylori; Link; Malignant Neoplasms; Measures; Modeling; Molecular; Molecular Evolution; Molecular Profiling; Natural Selections; Nucleotides; Numbers; Pathway interactions; Phenotype; Population; Population Genetics; Prevention; Process; Public Health; Quantitative Trait Loci; Recombinants; Recording of previous events; Research; Resolution; Role; Sequence Analysis; System; Testing; Variant; Work; fitness; genetic analysis; human disease; research study; trait

DESCRIPTION (provided by applicant): Although recent advances in genomics have revealed a tremendous amount of nucleotide polymorphism, little is known about why genes segregate for variants that influence quantitative traits. This proposed research seeks to determine which evolutionary processes influence natural genetic variation for complex traits. In order to identify and interpret allelic variants underlying QTLs, this experimental system has four fundamental characteristics: 1) An ecologically important complex trait, 2) a clonable QTL in a known pathway, 3) undisturbed environments where fitness can be measured, and 4) undisturbed populations which retain sequence signatures of temporal and geographic history. These evolutionary analyses use biochemistry to connect genotype with phenotype, and use natural environments to measure fitness. Nevertheless, the fundamental justification for this work is to test hypotheses regarding the evolutionary processes which influence complex trait variation. Towards this goal, a QTL will be cloned which influences ecologically important quantitative variation. Near isogenic lines with better than single gene resolution will be used to measure the fitness and phenotypes of functionally divergent alleles grown in their natural environments. Finally, sequence variation will be used to infer historical and evolutionary influences on allelic variation in undisturbed populations. Public Health Relevance: This proposed research will contribute to our understanding of complex trait variation, which is one of the primary causes of human disease. In addition, these experiments examine the genetics of glucosinolates, which are a focus of biomedical research due to their role in prevention of many forms of cancer, as well as gastritis attributable to Helicobacter pylori.

描述（由申请人提供）：尽管基因组学的最新进展揭示了大量的核苷酸多态性，但人们对影响数量性状的基因分离变异的原因知之甚少。这项拟议的研究旨在确定哪些进化过程影响复杂性状的自然遗传变异。为了识别和解释QTL的等位基因变异，该实验系统具有四个基本特征：1)具有重要的生态复杂性状；2)在已知途径中具有可克隆的QTL； 3)可以测量适应度的未受干扰的环境；4)未受干扰的种群保留了时间和地理历史的序列特征。这些进化分析使用生物化学将基因型与表型联系起来，并使用自然环境来测量适应性。然而，这项工作的基本理由是测试关于影响复杂性状变异的进化过程的假设。为了实现这一目标，将克隆一个影响生态重要数量变异的QTL。具有比单基因分辨率更好的近等基因系将用于测量在其自然环境中生长的功能分化等位基因的适合度和表型。最后，序列变异将用于推断未受干扰种群中等位基因变异的历史和进化影响。公共卫生相关性：这项拟议的研究将有助于我们理解复杂的性状变异，这是人类疾病的主要原因之一。此外，这些实验还研究了硫代葡萄糖苷的遗传学，由于其在预防多种癌症以及幽门螺杆菌引起的胃炎方面的作用，硫代葡萄糖苷成为生物医学研究的焦点。