Mackay Trudy F C, Anholt Robert R H
Department of Genetics, North Carolina State University, Raleigh, North Carolina, 27695, USA.
Annu Rev Genomics Hum Genet. 2006;7:339-67. doi: 10.1146/annurev.genom.7.080505.115758.
Understanding the genetic and environmental factors affecting human complex genetic traits and diseases is a major challenge because of many interacting genes with individually small effects, whose expression is sensitive to the environment. Dissection of complex traits using the powerful genetic approaches available with Drosophila melanogaster has provided important lessons that should be considered when studying human complex traits. In Drosophila, large numbers of pleiotropic genes affect complex traits; quantitative trait locus alleles often have sex-, environment-, and genetic background-specific effects, and variants associated with different phenotypic are in noncoding as well as coding regions of candidate genes. Such insights, in conjunction with the strong evolutionary conservation of key genes and pathways between flies and humans, make Drosophila an excellent model system for elucidating the genetic mechanisms that affect clinically relevant human complex traits, such as alcohol dependence, sleep, and neurodegenerative diseases.
由于存在许多相互作用且个体效应较小的基因，其表达对环境敏感，了解影响人类复杂遗传性状和疾病的遗传和环境因素是一项重大挑战。利用黑腹果蝇可用的强大遗传方法剖析复杂性状，提供了一些重要经验教训，在研究人类复杂性状时应予以考虑。在果蝇中，大量的多效基因影响复杂性状；数量性状基因座等位基因通常具有性别、环境和遗传背景特异性效应，与不同表型相关的变异存在于候选基因的非编码区和编码区。这些见解，再加上果蝇和人类之间关键基因和途径的强烈进化保守性，使果蝇成为阐明影响临床相关人类复杂性状（如酒精依赖、睡眠和神经退行性疾病）遗传机制的优秀模型系统。
