EVOLUTIONARY HISTORY OF THE MOUSE T COMPLEX--A MOLECULAR GENETICS APPROACH

小鼠T复合体的进化史——分子遗传学方法

• 批准号: 6488251
• 负责人: MARK A ERHART
• 金额: $ 34.88万
• 依托单位: CHICAGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6488251
• 关键词: Mus musculus; aggression; alleles; animal population genetics; autoradiography; biochemical evolution; chromosome aberrations; developmental genetics; gene expression; gene frequency; genetic library; genetic mapping; genetic recombination; genetic transcription; genome; lethal genes; molecular cloning; nucleic acid sequence; phenotype; polymerase chain reaction; radiation genetics; restriction fragment length polymorphism; sex behavior; statistics /biometry

The region of mouse Chromosome 17 (Char 17) known as the t complex offers a model system in which important questions about mammalian genome organization and evolution can be addressed. The t complex is a naturally occurring chromosome variant that is found in virtually all populations of mice belong to the Mus musculus group. The field of mammalian genetics as a whole, and human genetics in particular, greatly benefit from the work on the t complex. The t complex is inherently fascinating not only because it is home to genes that influence important processes (sperm development, fertilization, embryonic viability, development of the vertebral column, and a number of mouse behaviors, such as male aggression and female mate choice) but because it also provides a model system for genome analysis-specifically the relationship between genome sequences and gene function. We will use comparative DNA sequence analysis of selected clones from two loci as a means of contemplating the picture of the origin of the t complex. We have developed a comparative DNA sequence analysis of selected clones from two loci as a means of completing the picture of the origin of the t complex. Using an oligonucleotide screening method that has allowed us to identify genomic clones from a discrete segment of Chr 17, we hope to characterize novel portions of the t complex orthologous region of Mus spretus. Another resource developed by us, a series of mouse lines congenic for discrete and overlapping segments of the proximal portion of Chr 17 will allow genetic tests for particular gene functions. Finally, the influence of the t complex on mouse behavior will be examined, by laboratory testing of the congenic mice for male aggression and female mate choice. These experiments may eventually result in the cloning of the genes responsible for these traits. An important potential outcome of this work is the application of lessons learned from studying the mouse t complex to the Human Genome Project: namely, that even when a genomic segment is subjected to exhaustive genetic analysis or DNA sequence analysis, structure-function relationships often remain elusive, requiring novel approaches in order to uncover these relationships.

小鼠17号染色体（Char 17）上被称为t复合体的区域提供了一个模型系统，在这个模型系统中，有关哺乳动物基因组组织和进化的重要问题可以得到解决。t复合体是一种自然发生的染色体变异，几乎在所有属于小家鼠组的小鼠种群中都有发现。哺乳动物遗传学作为一个整体，特别是人类遗传学，极大地受益于t复合体的研究。这个复合体本身就很吸引人，不仅因为它是影响重要过程（精子发育、受精、胚胎活力、脊柱发育和许多小鼠行为，如雄性攻击性和雌性配偶选择）的基因的所在地，而且因为它还为基因组分析提供了一个模型系统——特别是基因组序列和基因功能之间的关系。我们将使用比较DNA序列分析的选择克隆从两个位点作为一种手段，考虑图片的起源t复合体。我们已经开发了一个比较的DNA序列分析选择克隆从两个位点作为一种手段完成的图片的起源t复合体。使用寡核苷酸筛选方法，使我们能够从Chr 17的离散片段中识别基因组克隆，我们希望表征鼠t复合体同源区域的新部分。我们开发的另一种资源是，一系列小鼠系同源于Chr 17近端部分的离散和重叠片段，这将允许对特定基因功能进行基因测试。最后，t复合体对小鼠行为的影响将被检验，通过实验室测试基因小鼠的雄性攻击性和雌性配偶选择。这些实验可能最终导致克隆这些性状的基因。这项工作的一个重要的潜在结果是将研究小鼠t复合体的经验教训应用于人类基因组计划：即，即使基因组片段进行了详尽的遗传分析或DNA序列分析，结构-功能关系往往仍然难以捉摸，需要新的方法来揭示这些关系。