Natural selection and DNA sequence variation in Mus

小鼠的自然选择和 DNA 序列变异

基本信息

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
项目类别：
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

项目摘要

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）：进化遗传学的主要目标是了解选择如何塑造DNA序列变化的模式，并最终将DNA序列变体连接到影响适应性的表型。解决这个问题的一种有希望的方法是研究最近将其范围扩展到新环境的物种，以寻找等位基因频率和环境变量的相关变化。这种研究环境适应的方法已在果蝇中成功使用，在果蝇中，在宽阔的纬度样带上都可以看到各种不同的分子和表型性状的细胞变异。关于人类的最新研究还将等位基因频率的变化与常见代谢性疾病的候选基因的气候变量联系起来，这表明这种方法也可能使我们能够识别重要的疾病基因。房屋老鼠Mus Musculus为研究人类的最佳哺乳动物模型提供了一个独特的机会来研究环境适应。拟议的研究将对北美和南美各种纬度和海拔地区的260只野生小鼠进行采样。采样设计包括高度和纬度的配对样品。所有小鼠将使用新的Affymetrix SNP芯片进行基因分型，以鉴定植入基因组的候选区域，这些候选区域具有对不同环境和气候的适应性基因。然后，将重新确定选定的基因组区域以识别等位基因变体。小鼠为人类无法提供的功能测试提供了特定的机会。因此，提议的工作还将从极端环境中建立16种新的近交菌株，对其基因组进行序列，并提供对其表型的初步描述。这些资源将为将来的工作奠定舞台，将特定自适应变体与特定表型联系起来，其中许多可能与人类代谢疾病有关。