Natural selection and DNA sequence variation in Mus

小鼠的自然选择和 DNA 序列变异

• 批准号: 8600696
• 负责人: MICHAEL W. NACHMAN
• 金额: $ 38.94万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8600696
• 关键词: Accounting; Affect; Altitude; Animals; Architecture; Base Sequence; Bayesian Modeling; Behavioral; Candidate Disease Gene; Cataloging; Catalogs; Climate; Communities; Complex; DNA Resequencing; DNA Sequence; Data; Disease; Drosophila melanogaster; Environment; Future; Gene Frequency; Genes; Genetic; Genetic Variation; Genome; Genomics; Genotype; Goals; Haplotypes; House mice; Human; Inbred Strain; Inbred Strains Mice; Individual; Laboratories; Laboratory mice; Life; Link; Metabolic; Metabolic Diseases; Modeling; Molecular; Mouse Strains; Mouse-ear Cress; Mus; Mutation; Natural Selections; North America; Pattern; Phenotype; Population; Research; Resolution; Resources; Sampling; Sea; Shapes; Signal Transduction; South America; Specimen; Staging; Structure; Testing; Tissues; Variant; Work; base; cost effective; design; environmental adaptation; fitness; genetic variant; genome sequencing; human disease; screening; trait

DESCRIPTION (provided by applicant): A major goal of evolutionary genetics is to understand how selection shapes patterns of DNA sequence variation, and ultimately, to connect DNA sequence variants to phenotypes that affect fitness. One promising approach to this problem is to study species that have recently expanded their ranges into new environments, to look for correlated changes in allele frequencies and environmental variables. This approach to studying environmental adaptation has been used successfully in Drosophila melanogaster where clinal variation is seen for a variety of different molecular and phenotypic traits across broad latitudinal transects. Recent work on humans has also linked changes in allele frequency to climatic variables in candidate genes for common metabolic disorders, suggesting that this approach may also allow us to identify important disease genes. The house mouse, Mus musculus, provides a unique opportunity to study environmental adaptation in the best mammalian model for humans. The proposed research will sample 260 wild mice representing 26 populations across a range of latitudes and altitudes in both North and South America. The sampling design includes paired transects for both altitude and latitude. All mice will be genotyped using a new Affymetrix SNP chip to identify candidate regions of the genome harboring genes underlying adaptation to different environments and climates. Select genomic regions will then be resequenced to identify allelic variants. Mice offer specific opportunities for functional tests not available in humans. Thus, the proposed work will also establish 16 new inbred strains of mice from extreme environments, sequence their genomes, and provide a preliminary description of their phenotypes. These resources will set the stage for future work linking particular adaptive variants to specific phenotypes, many of which are likely to be relevant for human metabolic disorders.

描述（由申请人提供）：进化遗传学的一个主要目标是了解选择如何塑造DNA序列变异的模式，并最终将DNA序列变异与影响适应性的表型联系起来。解决这个问题的一个有希望的方法是研究最近将其范围扩展到新环境中的物种，以寻找等位基因频率和环境变量的相关变化。这种方法来研究环境适应已被成功地用于果蝇的倾斜变化被视为各种不同的分子和表型性状跨越广泛的纬度断面。最近对人类的研究也将等位基因频率的变化与常见代谢紊乱的候选基因中的气候变量联系起来，这表明这种方法也可以让我们识别重要的疾病基因。家鼠，小家鼠，提供了一个独特的机会，研究环境适应的最佳哺乳动物模型的人类。这项拟议中的研究将对260只野生小鼠进行采样，代表北美和南美不同纬度和海拔地区的26个种群。抽样设计包括海拔和纬度的配对样带。所有小鼠都将使用新的Affytek SNP芯片进行基因分型，以确定基因组中包含适应不同环境和气候的基因的候选区域。然后将对选择的基因组区域进行重新测序以鉴定等位基因变体。小鼠为人类无法进行的功能测试提供了特定的机会。因此，拟议的工作还将建立16个来自极端环境的新近交系小鼠，对其基因组进行测序，并对其表型进行初步描述。这些资源将为未来的工作奠定基础，将特定的适应性变体与特定的表型联系起来，其中许多可能与人类代谢障碍相关。