2016 Fiscal Year Annual Research Report
Genome assay using massive parallel sequencing
Project Area | Integral understanding of the mechanism of transcription cycle through quantitative, high-resolution approaches |
Project/Area Number |
24118007
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Research Institution | Yokohama City University |
Principal Investigator |
松本 直通 横浜市立大学, 医学研究科, 教授 (80325638)
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Co-Investigator(Kenkyū-buntansha) |
三宅 紀子 横浜市立大学, 医学部, 准教授 (40523494)
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Project Period (FY) |
2012-06-28 – 2017-03-31
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Keywords | 転写 / BAF複合体 / 点変異 / 遺伝子重複 |
Outline of Annual Research Achievements |
概要:次世代シーケンサー(NGS)を効率的に用いて転写サイクルの解明に資するゲノムアッセイを行うことを目的に,以下の項目で研究を進めた。 1. Ion Protonの稼働率向上に向けて:P2チップの登場を期待していたが、結果的には販売されず、これまでと同程度の出力に留まったため平成27年度と同様の使用量となった。 2. RNA-seq解析系の確立:RNA-seqについては、遺伝子変異の結果生じるトランスクリプト異常を鋭敏に検出するインフォーマティクス解析系を検討した。その結果STARを用いた解析で遺伝子異常によるトランスクリプト異常を高い検出感度で同定することが可能であった。 3. 転写サイクルに関わる遺伝子異常による疾患の解明:転写サイクル異常に関わる疾患として解明を進めているCoffin-Siris症候群はBAF複合体の5つのサブユニットをコードする遺伝子とBAF複合体の下流に位置する転写因子SOX11の点変異で惹起されることを解明することができた。この6つの遺伝子の中でARID1Bのみ欠失やtruncation変異を認めた。それ以外の5つの遺伝子ではいずれもミスセンス変異を呈した。平成28年度は、これらの遺伝子異常のコピー数解析を進め、現時点でCoffin-Siris症例の2例で遺伝子SMARCA2を含むゲノム領域の重複を認め、論文として発表した(Am J Med Genet Part A, 2017)。このことはBAF複合体の各サブユニットがそれぞれのタンパク量を最適化して複合体として調和を保って微細な転写調節を行っている可能性を示唆していると考えている。
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Research Progress Status |
28年度が最終年度であるため、記入しない。
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Strategy for Future Research Activity |
28年度が最終年度であるため、記入しない。
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Research Products
(43 results)
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[Journal Article] Ultratra-sensitve droplet digital PCR for detecting a low-prevalence somatic GNAQ mutation in Sturge-Weber syndrome.2016
Author(s)
Uchiyama Y, Nakashima M, Watanabe S, Miyajima M, Taguri M, Miyatake S, Miyake N, Saitsu H, Mishima H, Kinoshita A, Arai H, Yoshiura K, Matsumoto N*
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Journal Title
Sci Rep
Volume: 6
Pages: 22985
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] FDG-PET study of patients with Leigh syndrome.2016
Author(s)
Haginoya K*, Kaneta T, Togashi N, Hino-Fukuyo N, Kobayashi T, Uematsu M, Kitamura T, Inui T, Okubo Y, Takezawa Y, Anzai M, Endo W, Miyake N, Saitsu H, Matsumoto N,
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Journal Title
J Neurol Sci
Volume: 362
Pages: 309-313
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Pathogenic variants in PIGG cause intellectual disability with seizures and hypotonia.2016
Author(s)
Makrythanasis P#, Kato M# (# denotes equal contribution), Zaki MS, Saitsu H, Nakamura K, Santoni FA, Miyatake S, Nakashima M, Issa MY, Guipponi M, Letourneau A, Logan CV, Roberts N, Parry DA, Johnson CA, Matsumoto N, Hamamy H, Sheridan E, Kinoshita T, *Antonarakis SE, *Murakami Y (*co-correspondence).
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Journal Title
Am J Hum Genet
Volume: 98
Pages: 615-626
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Mislocalization of syntaxin-1 and impaired neurite growth observed in a human iPSC model for STXBP1-related epileptic encephalopathy.2016
Author(s)
Yamashita S, *Chiyonobu T, Yoshida M, Maeda H, Zuiki M, Kidowaki S, Isoda K, Morimoto M, Kato M, Saitsu H, Matsumoto N, Nakahata T, Saito MK, Hosoi H.
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Journal Title
Epilepsia
Volume: 57(4)
Pages: e81-86
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Detection of low-prevalence somatic TSC2 mutations in sporadic pulmonary lymphangioleiomyomatosis tissues by deep sequencing.2016
Author(s)
Fujita A, Ando K, Kobayashi E, Mitani K, Okudera K, Nakashima N, Miyatake S, Tsurusaki Y, Saitsu H, Seyama K, Miyake N*, Matsumoto N* (*: co-correspondence).
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Journal Title
Hum Genet
Volume: 135(1)
Pages: 61-68
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] De novo GABRA1 mutations in Ohtahara and West syndromes.2016
Author(s)
Kodera H#, Ohba C# (# denotes equal contribution), Kato M, Maeda T, Araki K, Tajima D, Matsuo M, Hino-Fukuyo N, Kohashi K, Ishiyama A, Takeshita S, Motoi H, Kitamura T, Kikuchi A, Tsurusaki Y, Nakashima M, Miyake N, Sasaki M, Kure S, Haginoya K, *Saitsu H, *Matsumoto N (: co-correspondence).
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Journal Title
Epilepsia
Volume: 57(4)
Pages: 566-573
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] De novo missense mutations in NALCN cause developmental and intellectual impairment with hypotonia.2016
Author(s)
Fukai R, Saitsu H, Okamoto N, Sakai Y, Fattal-Valevski A, Masaaki S, Kitai Y, Torio M, Kojima-Ishii K, Ihara K, Nakashima M, Miyatake S, Tanaka F, Miyake N, *Matsumoto N.
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Journal Title
J Hum Genet
Volume: 61(5)
Pages: 451-455
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Dyschromatosis symmetrica hereditaria and Aicardi-Goutières syndrome 6 are phenotypic variants caused by ADAR1 mutations.2016
Author(s)
*Kono M, Matsumoto F, Suzuki Y, Suganuma M, Saitsu H, Ito Y, Fujiwara S, Moriwaki S, Matsumoto K, Matsumoto N, Tomita Y, Sugiura K, Akiyama M. Dyschromatosis symmetrica hereditaria and Aicardi-Goutières syndrome 6 are phenotypic variants caused by ADAR1 mutations.
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Journal Title
J Invest Dermatol
Volume: 136(4)
Pages: 875-8
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] De novo KCNH1 mutations in four patients with syndromic developmental delay, hypotonia and seizures.2016
Author(s)
Fukai R, Saitsu H, Tsurusaki Y, Sakai Y, Haginoya K, Takahashi K, Hubshman MW, Okamoto N, Nakashima M, Tanaka F, Miyake N, Matsumoto N*.
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Journal Title
J Hum Genet
Volume: 61(5)
Pages: 381-387
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Two cases of early-onset myoclonic seizures with continuous parietal delta activity caused by EEF1A2 mutations.2016
Author(s)
Inui T*, Kobayashi S, Ashikari Y, Sato R, Endo W, Uematsu M, Oba H, Saitsu H, Matsumoto N, Kure S, Haginoya K
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Journal Title
Brain Dev
Volume: 38(5)
Pages: 520-4
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay.2016
Author(s)
#Saitsu H, #Watanabe M, #Akita T (# denotes equal contribution), Ohba C, Sugai K, Ong WP, Shiraishi H, Yuasa S, Matsumoto H, Beng KT, Saitoh S, Miyatake S, Nakashima M, Miyake N, Kato M, Fukuda A*, Matsumoto N* (*: co-corresponding).
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Journal Title
Sci Rep
Volume: 6
Pages: 30072
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] De Novo Truncating Mutation of TRIM8 Causes Early-Onset Epileptic Encephalopathy.2016
Author(s)
*Sakai Y#, Fukai R# (# denotes equal contribution), Matsushita Y, Miyake N, Saitsu H, Akamine S, Torio M, Sasazaki M, Ishizaki Y, Sanefuji M, Torisu H, Shaw CA, Matsumoto N, Hara T.
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Journal Title
Ann Hum Genet
Volume: 80(4)
Pages: 235-240
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] SMARCE1, a rare cause of Coffin-Siris Syndrome: Clinical description of three additional cases.2016
Author(s)
Zarate YA, Bhoj E, Kaylor J, Li D, Tsurusaki Y, Miyake N, Matsumoto N, Phadke S, Escobar L, Irani A, Hakonarson H, Schrier Vergano SA*.
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Journal Title
Am J Med Genet A
Volume: 170(8):
Pages: 1967-1973
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] De novo p.Arg756Cys mutation of ATP1A3 causes an atypical form of alternating hemiplegia of childhood with prolonged paralysis and choreoathetosis.2016
Author(s)
Kanemasa H#, Fukai R# (# denotes equal contribution), *Sakai Y, Torio M, Miyake N, Lee S, Ono H, Akamine S, Nishiyama K, Sanefuji M, Ishizaki Y, Torisu H, Saitsu H, Matsumoto N, Hara T.
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Journal Title
BMC Neurol.
Volume: 16
Pages: 174
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] The first Japanese case of leukodystrophy with ovarian failure arising from novel compound heterozygous AARS2 mutations.2016
Author(s)
Hamatani M, Jingami N, Tsurusaki Y, Shimada S, Shimojima K, Asada-Utsugi M, Yoshinaga K, Uemura N, Yamashita H*, Uemura K*, Takahashi R, Matsumoto N, Yamamoto T.
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Journal Title
J Hum Genet
Volume: 61(10)
Pages: 899-902
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Diagnosis of pancreatic lesions collected by endoscopic ultrasound-guided fine-needle aspiration using next-generation sequencing.2016
Author(s)
Kameta E, Sugimori K, Kaneko T, Ishii T, Miwa H, Sato T, Ishii Y, Sue S, Sasaki T, Yamashita Y, Shibata W, Matsumoto N, Maeda S*.
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Journal Title
Oncol Lett.
Volume: 12(5)
Pages: 3875-3881
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Clinical features of SMARCA2 duplication overlap with Coffin-Siris syndrome.2016
Author(s)
Miyake N*, Abdel-Salam G, Yamagata T, Eid MM, Osaka H, Okamoto N, Mohamed AM, Ikeda T, Afifi HH, Piard J, van Maldergem L, Mizuguchi T, Miyatake S, Tsurusaki Y, Matsumoto N* (co-correspondence).
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Journal Title
. Am J Med Genet A.
Volume: 170(10)
Pages: 2662-2670
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Novel HPS6 mutations identified by whole-exome sequencing in two Japanese sisters with suspected ocular albinism.2016
Author(s)
*Miyamichi D, Asahina M, Nakajima J, Sato M, Hosono K, Nomura T, Negishi T, Miyake N, Hotta Y, Ogata T, Matsumoto N.
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Journal Title
J Hum Genet.
Volume: 61(9)
Pages: 839-842
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Identification of biallelic LRRK1 mutations in osteosclerotic metaphyseal dysplasia and evidence for locus heterogeneity.2016
Author(s)
Iida A, Xing W, Docx MK, Nakashima T, Wang Z, Kimizuka M, Van Hul W, Rating D, Spranger J, Ohashi H, Miyake N, Matsumoto N, Mohan S, Nishimura G, Mortier G, *Ikegawa S.
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Journal Title
J Med Genet.
Volume: 53(8)
Pages: 568-74
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] WDR45 mutations in three male patients with West syndrome.2016
Author(s)
Nakashima M, Takano K, Tsuyusaki Y, Yoshitomi S, Shimono M, Aoki Y, Kato M, Aida N, Mizuguchi T, Miyatake S, Miyake N, Osaka H, Saitsu H, Matsumoto N.
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Journal Title
J Hum Genet.
Volume: 61(7)
Pages: 653-661
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Milder progressive cerebellar atrophy caused by biallelic SEPSECS mutations.2016
Author(s)
Iwama K, Sasaki M, Hirabayashi S, Ohba C, Iwabuchi E, Miyatake S, Nakashima M, Miyake N, Ito S, Saitsu H, Matsumoto N.
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Journal Title
J Hum Genet.
Volume: 61(6)
Pages: 527-31
DOI
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Mendelian Exome in Japan2016
Author(s)
Naomichi Matsumoto
Organizer
LMCE2016, Symposium 13
Place of Presentation
The-K Hotel, Seoul, Korea
Year and Date
2016-10-28 – 2016-10-28
Int'l Joint Research / Invited
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[Presentation] Rare variants in human diseases2016
Author(s)
Naomichi Matsumoto
Organizer
International Symposium on Genomic Medicine 2016
Place of Presentation
Samsung Medical Center, Seoul, Korea
Year and Date
2016-06-24 – 2016-06-24
Int'l Joint Research / Invited
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