Natural selection and DNA sequence variation in Mus

小鼠的自然选择和 DNA 序列变异

• 批准号: 7010359
• 负责人: MICHAEL W. NACHMAN
• 金额: $ 23.39万
• 依托单位: UNIVERSITY OF ARIZONA
• 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 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7010359
• 关键词: Mus musculus; animal genetic material tag; animal population genetics; autosome; genetic mapping; genetic screening; genetic strain; genotype; laboratory mouse; linkage disequilibriums; natural selections; nucleic acid sequence; reproduction; sex chromosomes; single nucleotide polymorphism; species difference; statistics /biometry

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（由申请人提供）：在可用的小鼠基因组的完整序列中，我们现在可以研究不同基因组区域自然种群的遗传变异，研究了这种变异的基础力，并开始识别功能变异。在小鼠的近交性实验室菌株中，对单核苷酸多态性（SNP）的描述进行了重大努力，但对这种变异与野生群体水平变化的关系几乎一无所知。例如，许多实验室小鼠SNP可能代表了穆斯家族和穆斯库鲁斯群岛之间的固定种间差异，而其他实验室的差异可能代表一个或两个物种中隔离的种内多态性。 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在九个常用的近交菌株中以及对野生小鼠的基因分型中的300个先前确定的300个SNP的基因分型中的测序相同的30个基因，（3）（3）文档模式，种核苷酸内多态性和种间差的核苷酸内部多态性和跨性别差的基因的较大差异（可能与已知的can canss SCAN相关）（可能是选择），该基因可能会选择（4）（4）。通过分析沿X染色体间隔100个标记的微卫星变化的自然选择，在1染色体上分析100个标记，（5）序列（5）序列的一系列窗户以定期间隔间隔间隔到几个基因座，从上述工作中识别为选择目标。将X染色体和常染色体上的三十个基因与人类这些相同基因的多态性调查进行比较。由于这些基因中的许多基因都在小鼠和人类的不同基因组环境中发现，因此这种比较将直接检验基因组情境是遗传变异模式的重要决定因素的假设。拟议的研究将提供对家长和穆斯卡卢斯氏菌天然种群核苷酸变化的首次全面描述，并将清楚地了解常用近交菌株之间的变化与自然种群变化之间的变化之间的关系。