Telomere Structure In Drosophila

我们对端粒结构和身份的遗传控制感兴趣，并专注于模式生物，果蝇。已知这种生物体中的突变会急剧增加或减少染色体末端端粒特异性反转录转座子的添加频率，表明这一过程受遗传控制。我们已经确定了一个基因，端粒延伸，它的突变增加了终端基因转换和靶向转位的频率，并利用位置信息克隆该基因。Tel基因位于3号染色体右臂的中间位置，约55 kb，包含5个基因。对这些基因的编码区进行测序并没有确定一个高概率的候选基因。观察到Tel突变在遗传上是显性的，并且该区域的缺失没有端粒延长表型，这表明突变是功能获得突变，可能在控制区域。下一代DNA测序已经在基因间区发现了三个小的索引，这些索引存在于突变型染色体中，而不存在于野生型对照中。

We are interested in the genetic control of telomere structure and identity, and have focused on the model organism, Drosophila melanogaster. Mutations in this organism are known that drastically increase or decrease the frequency of additions of telomere-specific retrotransposon to a chromosome end, suggesting that this process is under genetic control. We have identified one gene, Telomere elongation, which has mutations that increase the frequencies of both terminal gene conversion and targeted transposition, and are using positional information to clone the gene. The Tel gene maps to the middle of right arm of chromosome 3 to a region of approximately 55 kb, which includes five genes. Sequencing the coding regions of these genes did not identify a high probability candidate gene. The observations that the Tel mutations are genetically dominant and that deletions for the region do not have a telomere elongation phenotype suggest that the mutations are gain-of-function mutations and may be in controlling regions. Next generation DNA sequencing has identified three small indels in intergenic regions that are present in the mutant chromosome but not the wild type controls. Chromatin structure may regulate telomere length by controlling transcription of the telomeric retrotransposons and by controlling accessibility of the retroelements to the chromosome end. We have marked a HeT-A transposable element with a transcribed gene in order to follow the transposon as it moves from one chromosome end to another. The marked element has been transformed into animals, and we are attempting to force it to transpose to a chromosome end. If the assay works, it will allow us to investigate what genetic and environmental factors influence the rate of movement, either by classical retrotransposition or by telomeric gene conversion.