Natural selection and DNA sequence variation in Mus

小鼠的自然选择和 DNA 序列变异

• 批准号: 8003045
• 负责人: MICHAEL W. NACHMAN
• 金额: $ 18.63万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-20 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8003045
• 关键词: Address; Base Composition; Biological Assay; Candidate Disease Gene; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 15; Complex; DNA Sequence; DNA Sequence Analysis; Data; Demography; Disease; Environment; Equilibrium; Evolution; Frequencies; Genealogy; Genes; Genetic Polymorphism; Genetic Recombination; Genetic Structures; Genetic Variation; Genome; Genomics; Genotype; Goals; Guanine + Cytosine Composition; Haplotypes; House mice; Human; Inbred Strain; Inbred Strains Mice; Individual; Isochores; Laboratories; Link; Linkage Disequilibrium; Location; Microsatellite Repeats; Modeling; Molecular Evolution; Mouse Strains; Mus; Mus musculus domesticus; Mutation; Natural Selections; Nucleotides; Orthologous Gene; Pattern; Phenotype; Population; Population Genetics; Positioning Attribute; Process; Publishing; Relative (related person); Reproduction; Research; Scanning; Series; Shapes; Single Nucleotide Polymorphism; Site; Slide; Structure; Surveys; Testing; Variant; Work; X Chromosome; autosome; density; genome sequencing; male; mouse genome; trait

DESCRIPTION (provided by applicant): With the complete sequence of the mouse genome available, we can now study genetic variation from natural populations in different genomic regions, investigate the forces underlying that variation, and begin to identify functional variants. Significant efforts have gone into the description of single nucleotide polymorphisms (SNPs) among inbred laboratory strains of mice, yet little is known of how this variation relates to population-level variation in the wild. For example, many lab mouse SNPs may represent fixed interspecific differences between Mus domesticus and Mus musculus, while others may represent intraspecific polymorphisms segregating in one or both species. The proposed research will (1) document patterns of nucleotide variation in natural populations of M. domesticus and M. musculus by sequencing 5-10 kb at each of 15 genes on the X chromosome and 15 genes on autosomes and also sequencing these same genes in two closely related species of mice, M. spretus and M. caroli, (2) relate genetic variation in these natural populations to genetic variation among inbred strains by sequencing the same 30 genes in nine commonly used inbred strains and also by genotyping the wild mice for a set of 300 SNPs previously ascertained in inbred strains, (3) document patterns of intraspecific nucleotide polymorphism and interspecific divergence for a set of 12 genes known to be involved in reproduction and chosen as likely targets for selection, (4) provide a large-scale scan for the effects of natural selection by assaying microsatellite variation at 100 markers spaced along the X chromosome and 100 markers on chromosome 1, and (5) sequence a series of windows spaced at regular intervals adjacent to several loci identified as targets of selection from the work described above. The thirty genes on the X chromosome and autosomes will be compared to published polymorphism surveys of these same genes in humans. Because many of these genes are found in different genomic environments in mice and humans, this comparison will provide a direct test of the hypothesis that genomic context is an important determinant of patterns of genetic variation. The proposed research will provide the first comprehensive description of nucleotide variation in natural populations of M. domesticus and M. musculus and will provide a clear picture of the relationship between variation among commonly used inbred strains and variation in natural populations.

描述(申请人提供)：有了小鼠基因组的完整序列，我们现在可以研究不同基因组区域自然种群的遗传变异，调查这种变异背后的力量，并开始识别功能变异。在描述近交系小鼠实验室品系中的单核苷酸多态(SNPs)方面已经做了大量的工作，但对这种变异如何与野生种群水平的变化相关的了解很少。例如，许多实验室小鼠的SNP可能代表了家鼠和小鼠之间固定的种间差异，而其他SNP可能代表了一个或两个物种中分离的种内多态。建议的研究将(1)通过对X染色体上的15个基因和常染色体上的15个基因中的每一个进行5-10kb的测序，并还在两个近缘种小鼠中对这些相同的基因进行测序，来记录家蝇和肌肉支原体自然群体中的核苷酸变异模式，(2)通过对9个常用近交系中的相同30个基因进行测序，以及通过对野生小鼠进行基因分型，将这些自然群体中的遗传变异与近交系之间的遗传变异联系起来，以获得先前在近交系中确定的一组300个SNP，(3)记录一组已知与生殖有关并被选为可能的选择目标的12个基因的种内核苷酸多态和种间差异的模式，(4)通过分析沿X染色体分布的100个标记和1号染色体上的100个标记的微卫星变异来提供对自然选择效应的大规模扫描，以及(5)对上述工作中被确定为选择目标的几个座位附近以规则间隔隔开的一系列窗口进行排序。X染色体和常染色体上的30个基因将与发表的人类相同基因的多态调查进行比较。由于这些基因中的许多是在老鼠和人类不同的基因组环境中发现的，这种比较将直接检验基因组环境是遗传变异模式的重要决定因素的假设。这项研究将首次全面描述家蝇和肌肉鼠自然种群中的核苷酸变异，并将清楚地描述常用近交系之间的变异与自然种群中的变异之间的关系。