Analysis of large and small colony L5178Y tk-/- mouse lymphoma mutants by loss of heterozygosity (LOH) and by whole chromosome 11 painting: detection of recombination.
Analysis of large and small colony L5178Y tk-/- mouse lymphoma mutants by loss of heterozygosity (LOH) and by whole chromosome 11 painting: detection of recombination.
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通过杂合性缺失 (LOH) 和整个 11 号染色体染色分析大和小菌落 L5178Y tk-/- 小鼠淋巴瘤突变体：重组检测。
DOI：
10.1093/mutage/13.5.461
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发表时间：
1998
期刊：
影响因子：
2.7
通讯作者：
Hozier,JC
中科院分区：
文献类型：
--
作者：
Liechty,MC;Scalzi,JM;Sims,KR;CrosbyJr,H;Spencer,DL;Davis,LM;Caspary,WJ;Hozier,JC
对源自 L5178Ytk+/- 小鼠淋巴瘤细胞 11 号染色体上 28 个异形微卫星位点的 122 个自发大集落和小集落突变体的分析表明，杂合性广泛丢失 (LOH) 在大集落和小集落突变体中都很常见，从而消除了大多数 11 号染色体基因座作为假定生长控制基因座的候选者。这些结果与历史细胞遗传学数据相结合，表明假定的生长控制位点位于胸苷激酶 (Tk1) 基因的远端，靠近端粒。 37 个突变体与 11 号染色体特异性全染色体涂色探针杂交，用于重排分析。一般来说，绘画证实了早期的观察结果，即大菌落突变体核型正常，而小菌落突变体经常有可检测到的重排。 Tk1 远端的点探针没有显示小集落突变体中染色体断裂的证据，这些突变体在整个 11 染色中表现正常并且没有 LOH。因此，大菌落突变体和小菌落突变体之间的分子差异仍然未知。提出了与我们的发现一致的解释大和小菌落突变体的模型，包括假定的生长控制基因的丢失、染色体断裂/修复的差异机制以及作为小菌落突变体的平面的第二位点突变。绘画揭示了易位和非整倍性，并表明不分离并不是完全 LOH 的常见解释。最常见的发现是 LOH 的大部分区域不是由缺失引起的，这表明这些细胞可以检测重组事件以及之前观察到的染色体重排、缺失和点突变。
Analysis of 122 spontaneous large and small colony mutants derived from L5178Ytk+/−mouse lymphoma cells at 28 heteromorphic microsatellite loci on chromosome 11 showed that extensive loss of heterozygosity (LOH) is common in both large colony and small colony mutants, eliminating most chromosome 11 loci as candidates for a putative growth control locus. These results, in conjunction with historical cytogenetic data, suggest that a putative growth control locus lies distal to the thymidine kinase (Tk1) gene, near the telomere. Thirty seven mutants were hybridized with a chromosome 11-specific whole chromosome painting probe for analysis of rearrangements. Generally, painting confirmed earlier observations that large colony mutants are karyotypically normal, whereas small colony mutants frequently have detectable rearrangements. A point probe distal toTk1revealed no evidence of chromosome breakage in small colony mutants that appeared normal on whole 11 painting and had no LOH. Therefore, the molecular difference between large and small colony mutants remains unknown. Models to explain large and small colony mutants consistent with our findings are presented, including loss of a putative growth control gene, differential mechanisms of chromosome breakage/repair and second site mutations as planations for small colony mutants. Painting revealed translocations and aneuploidy and showed that non-disjunction was not a common explanation for complete LOH. The most common finding was that large regions of LOH do not result from deletions, demonstrating that these cells can detect recombination events as well as previously observed chromosomal rearrangements, deletions and point mutations.