Testicular germ cell tumors in mice: new ways to study a genetically complex trait.
Testicular germ cell tumors in mice: new ways to study a genetically complex trait.
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DOI：
10.1007/978-1-60327-214-8_15
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发表时间：
2008
影响因子：
--
通讯作者：
Jason D. Heaney;J. Nadeau
中科院分区：
文献类型：
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作者：
Jason D. Heaney;J. Nadeau
睾丸生殖细胞肿瘤（TGCT）是影响年轻男性的最常见癌症。虽然TGCT是常见的，并且易感性的遗传成分异常强，但在人类中发现TGCT易感基因一直具有挑战性。129/Sv近交系小鼠是研究TGCT易感性遗传控制的重要实验模型。它是唯一一种具有明显自发TGCT频率的近交系小鼠品系。129/Sv男性的TGCT与人类儿科TGCT具有各种发育和组织学特征。与人类一样，129/Sv的易感性是一种遗传复杂的性状，对于传统的遗传方法来说过于复杂。然而，当在129/Sv背景下同源或同基因时，几种遗传变体充当TGCT易感性的遗传修饰剂。基于这些修饰基因的替代实验方法可用于解开TGCT易感性的复杂遗传控制。我们讨论了修饰基因在遗传互作试验和致敏多基因性状分析中的应用，以了解小鼠TGCT易感性的复杂遗传学和生物学。
Testicular germ cell tumors (TGCTs) are the most common cancer affecting young men. Although TGCTs are common and the genetic component of susceptibility is unusually strong, discovery of TGCT susceptibility genes in humans has been challenging. The 129/Sv inbred mouse strain is an important experimental model for studying the genetic control of TGCT susceptibility. It is the only inbred mouse strain with an appreciable frequency of spontaneous TGCTs. TGCTs in 129/Sv males share various developmental and histological characteristics with human pediatric TGCTs. As in humans, susceptibility in 129/Sv is a genetically complex trait that is too complex for conventional genetic approaches. However, several genetic variants, when congenic or isogenic on the 129/Sv background, act as genetic modifiers of TGCT susceptibility. Alternative experimental approaches based on these modifier genes can be used to unravel the complex genetic control of TGCT susceptibility. We discuss the application of modifier genes in genetic interaction tests and sensitized polygenic trait analyses toward the understanding of the complex genetics and biology of TGCT susceptibility in mice.