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首页> 外文期刊>Molecular cytogenetics >Juxtaposition of heterochromatic and euchromatic regions by chromosomal translocation mediates a heterochromatic long-range position effect associated with a severe neurological phenotype
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Juxtaposition of heterochromatic and euchromatic regions by chromosomal translocation mediates a heterochromatic long-range position effect associated with a severe neurological phenotype

机译：染色体易位对异色和常色区域的并置介导了与严重神经系统表型有关的异色远程位置效应

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Background The term "position effect" is used when the expression of a gene is deleteriously affected by an alteration in its chromosomal environment even though the integrity of the protein coding sequences is maintained. We describe a patient affected by epilepsy and severe neurodevelopment delay carrying a balanced translocation t(15;16)(p11.2;q12.1)dn that we assume caused a position effect as a result of the accidental juxtaposition of heterochromatin in the euchromatic region. Results FISH mapped the translocation breakpoints (bkps) to 15p11.2 within satellite III and the 16q12.1 euchromatic band within the ITFG1 gene. The expression of the genes located on both sides of the translocation were tested by means of real-time PCR and three, all located on der(16), were found to be variously perturbed: the euchromatic gene NETO2/BTCL2 was silenced, whereas VPS35 and SHCBP1, located within the major heterochromatic block of chromosome 16q11.2, were over-expressed. Pyrosequencing and chromatin immunoprecipitation of NETO2/BTCL2 and VPS35 confirmed the expression findings. Interphase FISH analysis showed that der(16) localised to regions occupied by the beta satellite heterochromatic blocks more frequently than der(15). Conclusions To the best of our knowledge, this is the first report of a heterochromatic position effect in humans caused by the juxtaposition of euchromatin/heterochromatin as a result of chromosomal rearrangement. The overall results are fully in keeping with the observations in Drosophila and suggest the occurrence of a human heterochromatin position effect associated with the nuclear repositioning of the der(16) and its causative role in the patient's syndromic phenotype.
机译：背景技术当基因的表达受到其染色体环境变化的有害影响时，即使保持蛋白质编码序列的完整性，也使用术语“位置效应”。我们描述了一名患有癫痫病和严重神经发育迟缓的患者，该患者带有平衡易位t（15; 16）（p11.2; q12.1）dn，我们认为这是由于常染色质中异染色质的意外并置导致位置效应地区。结果FISH将转座断点（bkps）定位到卫星III内的15p11.2和ITFG1基因内的16q12.1常染色体。通过实时PCR测试了位于易位两侧的基因的表达，发现三个都位于der（16）上的基因受到了不同的干扰：常染色体基因NETO2 / BTCL2被沉默，而VPS35 SHCBP1和SHCBP1，位于16q11.2号染色体的主要异色区中，过表达。 NETO2 / BTCL2和VPS35的焦磷酸测序和染色质免疫沉淀证实了表达结果。相间FISH分析表明，der（16）比der（15）更频繁地定位于β卫星异色块所占据的区域。结论据我们所知，这是关于由染色体重排导致的常染色质/异染色质并置引起的人类异色位置效应的首次报道。总体结果与果蝇中的观察结果完全一致，并表明与der（16）的核重定位有关的人类异染色质位置效应的发生及其在患者症状表型中的起因。

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