GENE ORGANIZATION: STRUCTURE-FUNCTION RELATIONSHIPS

了解基因组的组织是如何满足 对像哺乳动物这样复杂的有机体的特殊要求。目标是 这一建议的目的是研究DNA序列组织之间的关系 并在哺乳动物基因组中发挥作用。人类肌球蛋白重链基因 和散布的重复DNA序列将被研究，特别是作为 它们的位置和表达与结构基因的表达有关。这个 肌球蛋白重链(MHC)基因编码的蛋白质负责 肌肉和非肌肉系统的运动性。两者的MHC蛋白 系统具有非常相似的功能和结构，但它们的基因却非常相似 分歧性。非肌肉MHC基因将被分离并进行染色体定位。 非肌肉MHC基因的组织和序列将与 肌肉特异的MHC基因已被分离并部分 表征(Leinwand等人)1983年a&b)。一种体细胞遗传学 将采用一种方法来分析调节组织和 肌肉和非肌肉MHC基因的发育特异性表达。这个 MHC中特定重复DNA序列家族的组织 将确定多基因复合体(ES)以及肌肉特异性 测试的任何重复序列的表达。在分析 邻近区域内重复DNA序列的组织和功能 在MHC基因中，研究了MHC基因的组织和表达 分散在基因组中的重复序列将是 继续。重复DNA序列的相互关系与基因 肌肉和非肌肉肌球蛋白重链基因将提供更好的 理解基因组组织和功能之间的联系。

It is important to understand how the organization of the genome meets the specialized requirements of an organism as complex as the mammal. The goal of this proposal is to study the relationship of DNA sequence organization and function in the mammalian genome. The human myosin heavy chain genes and interspersed repetitive DNA sequences will be studied, particularly as their positions and expression relate to structural gene expression. The myosin heavy chain (MHC) genes code for proteins that are responsible for motility in muscle and nonmuscle systems. The MHC proteins from both systems have very similar function and structure, yet their genes are quite divergent. Nonmuscle MHC genes will be isolated and chromosomally mapped. The organization and sequence of nonmuscle MHC genes will be compared with muscle-specific MHC genes that have been isolated and partially characterized (Leinwand et al. 1983 a & b). A somatic cell genetic approach will be carried out to analyze factors that regulate tissue and developmental-specific expression of muscle and nonmuscle MHC genes. The organization of specific repetitive DNA sequence families in the MHC multigene complex(es) will be determined as well as the muscle-specific expression of any repetitive sequences tested. While analyzing the organization and function of repetitive DNA sequences within the vicinity of the MHC genes, the investigation of the organization and expression of the repetitive sequences scattered throughout the genome will be continued. The interrelationships of repetitive DNA sequences and the muscle and nonmuscle myosin heavy chain genes will provide a better understanding of the link between genomic organization and function.