Etiology of the most common constitutional translocation in human, t(11;22)

人类最常见的体质易位的病因学，t(11;22)

• 批准号: 14370775
• 负责人: KURAHASHI Hiroki
• 金额: $ 8.9万
• 依托单位: Fujita Health University (2003)Osaka University (2002)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370775/
• 关键词: chromosome; translocation; breakpoint; palindrome; cruciform; chromosome 11; chromosome 22; t(11;22); t(17;22); 神経線維腫症1型; 転座切断点; AT rich; PATRR

Constitutional t(11;22) is the only known recurrent non-Robertsonian translocation in human. In my previous study, I demonstrated that the breakpoints of t(11;22) were located within palindromic AT-rich repeats. (PATRR). I proposed that the PATRR forms cruciform structure as a mechanism for the translocation. Using translocation-specific PCR, I also identified de novo t(11;22) at high frequency in sperm samples obtained from healthy individuals. In the study of these two years, I have examined the breakpoints of two neurofibromatosis-type 1 (NF1) cases with t(17;22). The breakpoints on chromosome 22 were located within the PATRR where those of t(11;22) resided. The translocations disrupted NF1 gene on chromosome 17. I have localized the breakpoints within a novel PATRR at intron 31 of the gene (Am J Hum Genet, 2003). This added support to my hypothesis for mechanism of palindrome-mediated translocation. Next, I analyzed the tertiary structure of the cloned PATRR of chromosome 11. I demonstrated that the PATRR formed cruciform structure in vitro using 2-dimensional agarose,gel electrophoresis, nuclease sensitivity assay, electrophoresis mobility shift assay, and atomic force microscopy. I am currently creating model-system of the PATRR-mediated chromosomal translocationusing E. coli or yeast as hosts.

体质性t（11; 22）是目前已知的唯一一种人类非罗伯逊易位。在我以前的研究中，我证明了t（11; 22）的断点位于回文AT丰富的重复。（PATRR）。我认为PATRR形成十字形结构是其易位的一种机制。使用易位特异性PCR，我还确定了从头t（11; 22）在健康个体的精子样本中的高频率。在这两年的研究中，我检查了两个神经纤维瘤病1型（NF 1）病例的t（17; 22）断点。22号染色体上的断裂点位于t（11; 22）断裂点所在的PATRR内。易位破坏了17号染色体上的NF 1基因。我已经将断裂点定位在该基因内含子31的新型PATRR内（Am J Genet，2003）。这进一步支持了我关于回文介导易位机制的假说。接下来，我分析了克隆的11号染色体PATRR的三级结构。我证明，PATRR形成十字形结构在体外使用二维琼脂糖，凝胶电泳，核酸酶敏感性测定，电泳迁移率变动分析，和原子力显微镜。我目前正在利用大肠杆菌建立PATRR介导的染色体易位模型系统。大肠杆菌或酵母作为宿主。

项目成果

Takeda S, Kondo M, Sasaki J, Kurahashi H, Kano H, et al.: "Fukutin is required for maintenance of muscle integrity, cortical histiogenesis, and normal eye development"Human Molecular Genetics. 12・12. 1449-1459 (2003)

Takeda S、Kondo M、Sasaki J、Kurahashi H、Kano H 等：“Fukutin 是维持肌肉完整性、皮质组织发生和正常眼睛发育所必需的”人类分子遗传学 12・12。 ）

Takeda S, Kondo M, Sasaki J, Kurahashi H, Kano H, et al.: "Fukutin is required for maintenance of muscle integrity, cortical histiogenesis, and normal eye development"Human Molecular Genetics. 12. 1449-1459 (2003)

Takeda S、Kondo M、Sasaki J、Kurahashi H、Kano H 等人：“Fukutin 是维持肌肉完整性、皮质组织发生和正常眼睛发育所必需的”人类分子遗传学。

Ono I, Imai K, Tanaka-Taya K, Kurahashi H, Okada S.: "Decreased frequency of seizures in infantile spasms associated with lissencephaly by human herpes virus 7 infection"Pediatrics International. 44・2. 168-170 (2002)

Ono I、Imai K、Tanaka-Taya K、Kurahashi H、Okada S.：“与人类疱疹病毒 7 感染相关的无脑畸形的婴儿痉挛发作频率降低”国际儿科 44・2。

Kurahashi H, Shaikh TH, Takata M, Toda T, Emanuel BS: "The constitutional t(17;22): another translocation mediated by palindromic AT rich repeats"American Journal of Human Genetics. 72・3. 733-738 (2003)

Kurahashi H、Shaikh TH、Takata M、Toda T、Emanuel BS：“宪法 t(17;22)：由回文 AT 丰富重复介导的另一种易位”美国人类遗传学杂志 72・3 (2003)。

Toda T, Kobayashi K, Takeda S, Sasaki J, Kurahashi H, et al.: "Fukuyama-type congenital muscular dystrophy and abnormal glycosylation of a-dystroglycan"Basic Applied Miology. 13・6. 287-292 (2003)

户田T、小林K、武田S、佐佐木J、仓桥H等：“福山型先天性肌营养不良和α-肌营养不良症糖基化”基础应用生物学13・6（2003年）。