Pleiotropy revisited: molecular explanations of a classic concept.
Pleiotropy revisited: molecular explanations of a classic concept.
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多效性重温：经典概念的分子解释。
DOI：
10.1002/ajmg.1320340120
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Pyeritz,RE
中科院分区：
文献类型：
--
作者：
Pyeritz,RE
多效性通常是指单个突变基因对表型的多重影响。自从孟德尔定律被重新发现后不久，这个概念对医学遗传学的重要性就起起落落了。最初，认为表型的所有方面以及孟德尔综合征的所有表现都源于突变等位基因的单一功能（或功能障碍）的观点获得了优势。对多效性重要性的支持逐渐减少，并在20世纪40年代的一个基因-一个酶假说中达到最低点。对患有遗传性结缔组织疾病的哺乳动物和人类的研究表明，“真正的”多向性可能并不存在。然而，多效性相关性的消亡还为时过早。对基因组织、表达和突变的详细了解表明了多种机制，如多功能蛋白、信使RNA的选择性剪接和重叠编码序列，通过这些机制，在正常发育和功能、孟德尔综合征和体细胞突变的情况下，真正的多向性可能发生。此外，多效性的广义定义应包括由相邻基因功能异常引起的综合征，如通过大缺失、协调表达的调控元件突变或不太清楚理解的“位置效应”。因此，在非整倍体综合征的情况下使用多效性是不合适的。
As commonly used, pleiotropy refers to multiple effects on phenotype of a single mutant gene. The importance of this concept to medical genetics has waxed and waned since its formulation soon after the rediscovery of Mendel's laws. Initially, the view that all aspects of a phenotype, and hence all manifestations of a mendelian syndrome, derive from a single function (or dysfunction) of a mutant allele gained ascendancy. Support for the importance of pleiotropy gradually diminished, and reached a low point in the 1940s with the one gene‐one enzyme hypothesis. Studies of mammals and humans with heritable disorders of connective tissue sustained the notion that “genuine” pleiotropy probably did not exist. However, the demise of the relevance of pleiotropy was premature. Detailed understanding of gene organization, expression, and mutation indicates several mechanisms, such as multifunctional proteins, alternative splicing of messenger RNA, and overlapping coding sequences, through which genuine pleiotropy likely occurs in normal development and function, in mendelian syndromes, and in conditions due to somatic mutation. Furthermore, a broad definition of pleiotropy is warranted to subsume syndromes caused by abnormal function of contiguous genes, such as through large deletions, mutation of regulatory elements that coordinate expression, or less clearly understood “position effects.” Thus, the use of pleiotropy in the context of aneuploidy syndromes is not inappropriate.