Forward genetic approaches to understanding complex behaviors.
Forward genetic approaches to understanding complex behaviors.
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DOI：
10.1007/7854_2011_189
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发表时间：
2012
影响因子：
--
通讯作者：
Eisener-Dorman AF
中科院分区：
文献类型：
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作者：
Tarantino LM;Eisener-Dorman AF
基因的功能调控一直是生物医学研究的热点。即使对人类、小鼠和其他实验生物的基因组序列有了完整的了解，关于基因的功能和控制仍然有很多东西需要了解。使用敲除或转基因技术切除或过表达单个基因为许多基因提供了功能注释，但这些技术不能捕获现有实验小鼠群体中存在的广泛遗传变异。研究人员直到最近才开始真正理解由单核苷酸取代、插入、缺失、拷贝数变异、表观遗传变化（DNA甲基化、组蛋白修饰等）引起的自然发生的遗传变异。基因表达差异以及这种变异如何导致复杂的表型。在这一章中，我们将讨论不同的正向遗传方法的优点和局限性，捕获近交系小鼠品系中存在的遗传变异，并提出这些方法的实用性，影响复杂的行为表型的QTL定位。
Assigning function to genes has long been a focus of biomedical research. Even with complete knowledge of the genomic sequences of humans, mice and other experimental organisms, there is still much to be learned about gene function and control. Ablation or overexpression of single genes using knockout or transgenic technologies has provided functional annotation for many genes, but these technologies do not capture the extensive genetic variation present in existing experimental mouse populations. Researchers have only recently begun to truly appreciate naturally occurring genetic variation resulting from single nucleotide substitutions, insertions, deletions, copy number variation, epigenetic changes (DNA methylation, histone modifications, etc.) and gene expression differences and how this variation contributes to complex phenotypes. In this chapter, we will discuss the benefits and limitations of different forward genetic approaches that capture the genetic variation present in inbred mouse strains and present the utility of these approaches for mapping QTL that influence complex behavioral phenotypes.