A balanced chromosomal translocation affects the inner nucleus positioning of thederivative chromosomes or not.

染色体平衡易位是否影响衍生染色体的内核定位。

• 批准号: 18590311
• 负责人: WAKUI Keiko
• 金额: $ 2.52万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590311/
• 关键词: structural chromosomal abnormality; 3D-FISH analysis; gene; genome; position effects

In the case of a patient with a disease associated balanced chromosomal rearrangements (DBCRs), one of the gene that disrupted by chromosomal rearrangements is possible to be confirmed as a responsible gene of the disease. If there were no known genes at the breakpoints, we have considered that the clinical features of the patient were not related to the chromosomal rearrangements. But, we speculated that it is possible that chromosomal rearrangements lead to change the inner nucleus spatial organization of the genome, and the breakpoint site affects the disease causing gene in such DBCRs patients. We analyzed a case of a balanced translocation: t(11; 22) (q23; q11) by FISH on three-dimensionally preserved cells (3D FISH) using several BAC clones, which were closely mapped the breakpoints. We devised a new design of the combination of the probes which can be recognized four different targeted chromosomes each other in a 3D preserved nucleus. We verified that newly-devised probe design is effective for this research. And, we established a protocol using direct-labeled FISH method instead of using previous time-consuming indirect-labeled method. We reviewed the appropriate images for this research, and we improved how to obtain the ideal images of the nucleus, how to operate 3D computer software, etc. Although, we could not finish 3D FISH analysis for many patients with DBCRs, and could not show by means of evidence of our hypothesis in two years, we established new strategy to detect four kinds of chromosomes involving translocation in a 3D preserved nucleus for our research purpose. These are the important products to propose the new mechanism of DBCRs and position effects.

在患有与平衡染色体重排（DBCR）相关的疾病的患者的情况下，被染色体重排破坏的基因之一有可能被确认为该疾病的责任基因。如果在断裂点上没有已知的基因，我们认为患者的临床特征与染色体重排无关。但是，我们推测可能是染色体重排导致基因组的内核空间组织改变，并且断裂点位点影响了此类DBCR患者的致病基因。我们分析了一个平衡易位的情况下：t（11; 22）（q23; q11）的三维保存的细胞（3D FISH）使用几个BAC克隆，这是密切映射的断点。我们设计了一种新的探针组合设计，可以在三维保存的细胞核中相互识别四个不同的靶染色体。我们验证了新设计的探针设计是有效的这项研究。并且，我们建立了一种使用直接标记FISH方法的方案，而不是使用以前耗时的间接标记方法。我们回顾了适合本研究的图像，并改进了如何获得理想的细胞核图像，如何操作3D计算机软件等。虽然，我们无法对许多DBCR患者进行3D FISH分析，并且无法在两年内通过证据证明我们的假设，为了研究目的，我们建立了一种新的策略，在三维保存的细胞核中检测四种涉及易位的染色体。这些都是提出DBCR新机制和位置效应的重要产物。

项目成果

Molecular cytogenetic analysis of subtelomeric regions for a structural abnormalities of chromosome 12 and interpretations of the results

12 号染色体结构异常亚端粒区域的分子细胞遗传学分析及结果解释

• 发表时间: 2007
• 作者: Kinishita;Y.;Wakui;K.;Furui;T.;Shinogi;K.;Fukui;T.;Kawamura;R.;Yokoyama;S.;Higashi;H.;Fukushima;Y
• 通讯作者: Y

Discrepancies of the results between MLPA and FISH, and between MLPA kits, observed in a case of subtelomeric imbalances of chromosome 12.

在 12 号染色体亚端粒不平衡的情况下观察到 MLPA 和 FISH 之间以及 MLPA 试剂盒之间的结果存在差异。

• 发表时间: 2007
• 作者: Wakui K;Kinishita Y;Furui Y;Shinogi K;Fukui T;Kawamura R;Gondo N;Yokoyama S;Higashi H;Fukushima Y.
• 通讯作者: Fukushima Y.

A complex karyotype, including a three-way translocationg enerating a NUP98-HOXD13 transcript, in an infant with acute myeloid leukemia.

患有急性髓系白血病的婴儿的复杂核型，包括产生 NUP98-HOXD13 转录物的三向易位。

• 发表时间: 2007
• 期刊: Cancer Genet Cytogenet 176
• 作者: Hidaka E;Tanaka M;Matsuda K;Ishikawa-Matsumura M;Yamauchi K;Sano K;Honda T;Wakui K;Yanagisawa R;Nakazawa Y;Sakashita K;Shiohara M;Ishii E;Koike K.
• 通讯作者: Koike K.

A case of pure dup 9q34 confirmed by Subtelomeric FISH analyses

亚端粒 FISH 分析证实一例纯 dup 9q34

• 发表时间: 2007
• 作者: Imagawa;E.;Kosho;T.;Matsuda;K.;Higuchi;Y.;Uhara;M.;Yamauchi;K.;Katuyama;T.;Hidaka;E.;Shiba;N.;Arai;F.;Wakui;K.;Fukushima;Y
• 通讯作者: Y

Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes

患有严重进行性骨骼变化的女性下颌骨发育不良和新型 LMNA 突变

• 发表时间: 2007
• 期刊: Am J Med Genet 43A
• 作者: Kosho T;Takahashi J;Momose T;Nakamura A;Sakurai A;Wada T;Yoshida K;Wakui K;Suzuki T;Kasuga K;Nishimura G;Kato H;Fukushima Y
• 通讯作者: Fukushima Y