Natural selection and DNA sequence variation in Mus

小鼠的自然选择和 DNA 序列变异

• 批准号: 6870561
• 负责人: MICHAEL W. NACHMAN
• 金额: $ 23.91万
• 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/6870561
• 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）：随着小鼠基因组的完整序列的可用，我们现在可以研究不同基因组区域的自然种群的遗传变异，研究该变异的潜在力量，并开始鉴定功能变体。大量的工作已经投入到描述近交系实验室小鼠品系中的单核苷酸多态性（SNP）中，但很少有人知道这种变异与野生种群水平变异的关系。例如，许多实验室小鼠SNP可能代表小家鼠和小家鼠之间的固定种间差异，而其他SNP可能代表在一个或两个物种中分离的种内多态性。拟开展的研究将（1）记录自然群体中的核苷酸变异模式; Acetylticus和M.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5-10 kb的测序，以及对两种密切相关的小鼠物种M. spretus和M. caroli，（2）通过对9个常用近交系中相同的30个基因进行测序，并通过对野生小鼠进行先前在近交系中确定的一组300个SNP的基因分型，将这些自然群体中的遗传变异与近交系中的遗传变异联系起来，（三）记录了一组已知参与生殖的12个基因的种内核苷酸多态性和种间分歧的模式，选择作为可能的选择目标，（4）通过测定沿X染色体沿着分布的100个标记和1号染色体上的100个标记处的微卫星变异，提供自然选择效应的大规模扫描，和（5）对与从上述工作中鉴定为选择目标的几个基因座相邻的以规则间隔分布的一系列窗口进行测序。X染色体和常染色体上的30个基因将与已发表的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在小鼠和人类的不同基因组环境中被发现，这种比较将提供对基因组环境是遗传变异模式的重要决定因素这一假设的直接检验。这项研究将首次全面描述自然群体中的核苷酸变异。Acetylticus和M. musculus，并将提供一个常用的近交系和自然种群的变化之间的关系清晰的图片。