Fijneman R J, de Vries S S, Jansen R C, Demant P
The Netherlands Cancer Institute, Division of Molecular Genetics, Amsterdam, The Netherlands.
Nat Genet. 1996 Dec;14(4):465-7. doi: 10.1038/ng1296-465.
Many complex traits, including susceptibility to lung cancer, are controlled by multiple genes--quantitative trait loci (QTLs). We facilitated the mapping of QTLs by making use of recombinant congenic strains (RCS), a system of mouse inbred strains in which the genetic complexity is reduced, and by applying MQM-mapping (multiple-QTL models or marker-QTL-marker), a multilocus method with an increased power of detecting of individual QTLs and interacting QTLs (epistasis). The mouse strain O20 develops significantly larger N-ethyl-N-nitrosourea induced lung tumours than mice of the RC strain OcB-9 (ref. 5); the latter share approximately 87.5% of their genes with strain O20 and 12.5% with strain B10.O20 (refs 6,7). QTL analysis of 222 (OcB-9 x O20) F2 mice revealed four new loci that influence susceptibility to lung cancer (Sluc genes). They are involved in two significant, partly counteracting interactions which mask their individual main effects: Sluc1 (on chromosome 19) interacts with Sluc2 (chromosome 2), and Sluc3 (chromosome 6) interacts with Sluc4 (chromosome 11). Together with the data of van Wezel et al. in the accompanying report, our results indicate that interactions between tumour susceptibility genes are a common phenomenon which complicates their mapping.
许多复杂性状，包括肺癌易感性，是由多个基因——数量性状基因座（QTL）控制的。我们通过利用重组近交系（RCS）（一种降低了遗传复杂性的小鼠近交系系统）以及应用MQM定位法（多QTL模型或标记-QTL-标记）（一种能提高检测单个QTL和相互作用QTL（上位性）能力的多位点方法），推动了QTL的定位。与RC品系OcB-9的小鼠相比，O20品系的小鼠经N-乙基-N-亚硝基脲诱导产生的肺肿瘤要大得多（参考文献5）；后者与O20品系大约共享87.5%的基因，与B10.O20品系共享12.5%的基因（参考文献6、7）。对222只（OcB-9×O20）F2小鼠进行的QTL分析揭示了四个影响肺癌易感性的新基因座（Sluc基因）。它们参与了两种显著的、部分相互抵消的相互作用，这些相互作用掩盖了它们各自的主要效应：Sluc1（位于第19号染色体上）与Sluc2（第2号染色体）相互作用，Sluc3（第6号染色体）与Sluc4（第11号染色体）相互作用。连同随附报告中范·韦泽尔等人的数据，我们的结果表明肿瘤易感性基因之间的相互作用是一种常见现象，这使得它们的定位变得复杂。
