双極性障害型繰うつ病の疾患感受性遺伝子の解明

阐明双相抑郁症的疾病易感基因

• 批准号: 12204095
• 负责人: 工藤 純
• 金额: --
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12204095/
• 关键词: 21番染色体; 躁鬱病; 双極性障害; シーケンシング; DNMT3L; TMPRSS3; TRPC7; ANKRD3

躁うつ病とりわけ双極性障害に関しては遺伝要因の関与が強く示唆されてきたが、現在有力な候補領域とされているのは、18番染色体の動原体周辺部と21番染色体の長腕21q22のみである。本研究では我々が国際協力により決定した21番染色体のゲノム塩基配列を基盤として21q22にマップされた双極性障害型躁うつ病の疾患感受性遺伝子を解明することを目的として、以下の研究を行った。1.候補領域内のいかなる遺伝子も取り逃がすことのないよう21q22に残された3ヶ所計100kbのクローンギャップの解消を試み、新たに単離したクローン、PCRを用いて約40kbを埋めることに成功した。2.躁うつ病候補遺伝子の系統的単離:21q22のゲノムシーケンスの解析から推定された遺伝子についてcDNAの単離を進め、DNAメチルトランスフェラーゼ3類似遺伝子DNMT3L、DSCR5、DSCR6、WDリピート蛋白WDR4、グリセロール3リン酸透過酵素と推定されるSLC37A1/G3PP、膜貫通型セリンプロテアーゼTMPRSS3、UBAドメインとSH3ドメインを持つUBASH3A、ウロモジュリン類似蛋白UMODL1、マウユ精巣特異的遺伝子Tsga2のヒト型遺伝子TSGA2、Znフィンガー蛋白ZNF295、C21orf25、アンキリンリピートを持つキナーゼANKRD3など多数の新規候補遺伝子の構造を決定した。また既知・新規遺伝子のコーディング領域を増幅するプライマーを作成し、PCRの条件を設定した。3.躁うつ病家系01001について、新規カルシウムチャンネル蛋白TRPC7の遺伝子における多型の有無をSSCPによって解析した(Baronら、神庭らとの共同研究による)。候補遺伝子の探索は順調に進んだ。既に、領域内の大部分の遺伝子について完全な遺伝子構造が決定できた。今後は候補遺伝子の多型解析を重点的に進める。

The irritable disease, the double sexual disorder, the sexual disorder, the irritability, the strength, the frequency, the number of chromosomes, the number of chromosomes around the body, the number of chromosomes 21, the length of the wrist, the number of wrists, the number of chromosomes, the number of The purpose of this study is to determine the basis of chromosome 21, chromosome 21. 1. In the waiting field, you can get rid of the information in the field. In the field of waiting, you can get rid of the problems in the field of waiting. In the field of waiting, you can get rid of the problems in the field of waiting. In the field of waiting, you can get rid of the problems in the field of waiting. In the field of waiting, you can get rid of the problems in the field of waiting. In the field of waiting, you can get rid of the problems in the field of waiting. In the field of waiting, you can get rid of the problems in the field of waiting time. In the field of waiting, you can get rid of the problems in the field of waiting for information. In the field of waiting, you can get rid of the problems in the field of waiting for information. In the field of waiting, you can get rid of the problems in the field of waiting time. In the field of waiting, you two。 The isolation of the sub-system of dysphoric disorder: 21q22. The isolation of the sub-system is not known. It is presumed that the cDNA is isolated, and that the DNA is similar to DNMT3L, DSCR5, DSCR6, WD, protein WDR4, trypsin 3, enzyme-permeable enzyme SLC37A1/G3PP, membrane-permeable enzyme, TMPRSS3, and so on. The UBA profile is similar to the protein UMODL1, which is similar to the protein UMODL1, and to the TSGA2, the Zn, the Zn, the ANKRD3, and most of the new specifications, which are similar to protein UMODL1, TSGA2, and C21orf25, respectively. It is known that the new specification has a significant impact on the field, and the PCR condition settings have been created. 3. The pedigree with dysphoria and dysphoria in 01001 pedigrees with dysphoria, the new family members, the protein protein family, the protein phenotype, the protein phenotype, the protein phenotype, I am waiting for you to explore your son. Most of the people in the field have made decisions on the whole. In the future, we will look forward to the improvement of the key points of "polymorphic analysis".

项目成果

Berry,A. et al.: "Refined localization of autosomal recessive non-syndromic deafness DFNB10 locus using 34 novel microsatellite markers,genomic structure and exclusion of six known genes in the region."Genomics. 68(1). 22-29 (2000)

贝里，A.

Guipponi,M. et al.: "C21orf5,a novel human chromosome 21 gene,has a Caenorhabditis elegans ortholog(pad-1)reuired for embryonic patterning."Genomics. 68(1). 30-40 (2000)

吉波尼，M.

Wattenhofer,M. et al.: "Isolation and characterization of the UBASH3A gene on 21q22.3 encoding a potential nuclear protein with a novel combination of domains."Hum.Genet.. 108(2). 140-147 (2001)

瓦滕霍费尔，M.

Shibuya,K. et al.: "Isolation of two novel genes,DSCR5 and DSCR6,from Down syndrome critical region on human chromosome 21q22.2."Biochem.Biophys.Res.Commun. 271(3). 693-698 (2000)

涩谷，K.

Michaud,J. et al.: "Isolation and characterization of a human chromosome 21q22.3 gene(WDR4)and its mouse homologue that code for a WD-repeat protein."Genomics. 68(1). 71-79 (2000)

米肖，J.