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

被称为t复合体的小鼠17号染色体区域(Char 17)提供了一个模型系统，在这个模型系统中可以解决关于哺乳动物基因组组织和进化的重要问题。T复合体是一种自然产生的染色体变体，几乎在所有属于小鼠肌肉组的小鼠群体中都能找到。整个哺乳动物遗传学领域，特别是人类遗传学，都从t复合体的工作中受益匪浅。T复合体本身就令人着迷，不仅因为它是影响重要过程(精子发育、受精、胚胎存活、脊柱发育和许多老鼠行为，如雄性攻击性和雌性配偶选择)的基因的家园，还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。我们将使用来自两个基因座的选定克隆的比较DNA序列分析作为思考t复合体起源图景的一种手段。我们已经开发了对来自两个座位的选定克隆的比较DNA序列分析，作为完成t复合体起源的图像的一种手段。使用一种寡核苷酸筛选方法，使我们能够从Chr 17的离散片段中识别基因组克隆，我们希望表征小鼠t复杂直系同源区的新部分。我们开发的另一种资源，一系列与Chr 17近端离散和重叠片段同源的小鼠品系将允许对特定基因功能进行基因测试。最后，通过对同基因小鼠的雄性攻击和雌性配偶选择的实验室测试，将检验t复合体对小鼠行为的影响。这些实验可能最终导致对这些特征负责的基因的克隆。这项工作的一个重要的潜在成果是将从研究老鼠t复合体中学到的经验应用到人类基因组计划中：即即使一个基因组片段受到详尽的遗传分析或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。

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.