Gene interaction and single gene effects in colon tumour susceptibility in mice
Gene interaction and single gene effects in colon tumour susceptibility in mice
复制标题
小鼠结肠肿瘤易感性中的基因相互作用和单基因效应
作者：
T. Wezel;A. Stassen;C. J. Moen;A. Hart;M. Valk;P. Demant
为了剖析小鼠1中结肠肿瘤易感性的多基因控制，我们使用了一组20个CcS/Dem（CcS）重组同源（RC）菌株2。在BALB/cHeA（BALB/c）3的遗传背景下，每种CcS菌株均携带菌株STS/A（STS）基因组的约12.5%的独特随机子集。以前，应用26次注射1，2-二甲基肼（DMH）的方案，我们检测到2号染色体上的两个易感基因座Scc 1和Scc 2（参考文献4，5）。使用较短的肿瘤诱导程序，结合DMH和N-乙基-N-亚硝基脲（ENU）治疗，我们证明BALB/c，STS和大多数CcS菌株是相对耐药的。然而，菌株CcS-19是易感的，可能是由于BALB/c和STS等位基因在几个位点的组合。对192只（BALB/c × CcS-19）F2小鼠的分析显示，除了Scc 1/Scc 2区域外，还有3个新的易感基因座：1号染色体上的Scc 3、17号染色体上的Scc 4和18号染色体上的Scc 5。Scc 4和Scc 5没有明显的个体效应，但表现出很强的交互作用。它们的BALB/c和STS等位基因不是先验易感或抗性的，但一个位点的基因型决定了第二个位点的等位基因的效应，反之亦然。这些发现和随附的关于肺肿瘤易感性的论文6表明，基因座间的相互作用可能是肿瘤易感性的重要组成部分。
To dissect the multigenic control of colon tumour susceptibility in the mouse1 we used the set of 20 CcS/Dem (CcS) recombinant congenic (RC) strains2. Each CcS strain carries a unique, random subset of approximately 12.5% of the genome of strain STS/A (STS) on the genetic background of BALB/cHeA (BALB/c)3. Previously, applying a protocol of 26 injections of 1,2-dimethylhydrazine (DMH), we detected two susceptibility loci, Scc1 and Scc2, on chromosome 2 (refs 4, 5). Using a shorter tumour-induction procedure, combining DMH and N-ethyl-N-nitrosourea (ENU) treatment, we demonstrate that BALB/c, STS and most CcS strains are relatively resistant. The strain CcS-19, however, is susceptible, probably due to a combination of BALB/c and STS alleles at several loci. Analysis of 192 (BALB/c × CcS-19) F2 mice revealed, in addition to the Scc1/Scc2 region, three new susceptibility loci: Scc3 on chromosome 1, Scc4 on chromosome 17 and Scc5 on chromosome 18. Scc4 and Scc5 have no apparent individual effect, but show a strong reciprocal interaction. Their BALB/c and STS alleles are not a priori susceptible or resistant but the genotype at one locus determines the effect of the allele at the second locus and vice versa. These findings and the accompanying paper on lung tumour susceptibility6 show that interlocus interactions are likely to be an important component of tumour susceptibility.
适合进行种内杂交分型的小鼠遗传图谱。
影响因子：
3.3
作者：
Dietrich,W;Katz,H;Lincoln,SE;Shin,HS;Friedman,J;Dracopoli,NC;Lander,ES
通讯作者：
Lander,ES
实验物种多基因座连锁数据的统计评估及其与人类研究的相关性：在非肥胖糖尿病（NOD）小鼠和人胰岛素依赖性糖尿病（IDDM）中的应用。
影响因子：
9.8
作者：
Risch,N;Ghosh,S;Todd,JA
通讯作者：
Todd,JA