大量並行シーケンスによるゲノムアッセイ

2015 Fiscal Year Annual Research Report

• Project Area: Integral understanding of the mechanism of transcription cycle through quantitative, high-resolution approaches
• Project/Area Number: 24118007
• Research Institution: Yokohama City University
• Principal Investigator: 松本 直通 横浜市立大学, 医学(系)研究科(研究院), 教授 (80325638)
• Co-Investigator(Kenkyū-buntansha): 三宅 紀子 横浜市立大学, 医学部, 准教授 (40523494)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: BAF複合体 / 転写調節 / コピー数異常 / 遺伝子変異

Outline of Annual Research Achievements

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研究を進めている。平成27年度は、前年度に引き続き班内連携によりIon Protonの稼働率の向上に努めた。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本研究班で解明した。興味深いことにこの6つの遺伝子の中でARID1Bのみ欠失やtruncation変異を認める以外は、他の5つの遺伝子ではいずれも基本ミスセンス変異である。平成27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症例の複数例で遺伝子Aの重複を認める結果を得ている。このことはBAF複合体の各サブユニットが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。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

BAF複合体のサブユニット遺伝子とSOX11等を対象にコピー数異常解析を進めCoffin-Siris症候群症例に複数の遺伝子Aの重複を同定した。このことはBAF複合体の成り立ちが各サブユニットの調和のうえで正常な機能が保たれていることを示唆している。この所見は、新しい視点を提供したと考える。

Strategy for Future Research Activity

次世代シーケンサーを用いた技術開発とともにCoffin-Siris症候群の遺伝学的検索を通じてBAF複合体の遺伝子調節についてのメカニズムの解明に迫る研究を展開する。その他で様々な転写サイクルの異常を有する疾患を掘り起こし。機能面での解析を進めていく。

Research Products

• [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,
  • Journal Title: J Neurol Sci Volume: 362 Pages: 309-313
  • DOI: 10.1016/j.jns.2016.02.008.
  • Peer Reviewed / Int'l Joint Research
• [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).
  • Journal Title: Hum Genet Volume: 135(1) Pages: 61-68
  • DOI: 10.1007/s00439-015-1611-0.
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). (2016)
  • Author(s): Klionsky DJ, et al., Matsumoto N, et al..
  • Journal Title: Autophagy. Volume: 12(1) Pages: 1-222
  • DOI: 10.1080/15548627.2015.1100356
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] De novo DNM1 mutations in two cases of epileptic encephalopathy. (2016)
  • Author(s): Nakashima M, Kouga T, Lourenço CM, Shiina M, Goto T, Tsurusaki Y, Miyatake S, Miyake N, Saitsu H, Ogata K, Hitoshi Osaka H, Matsumoto N.
  • Journal Title: Epilepsia Volume: 57(1) Pages: e18-e23
  • DOI: 10.1111/epi.13257.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Renal complications in 6p duplication syndrome: microarray-based investigation of the candidate gene(s) for the development of congenital anomalies of the kidney and urinary tract (CAKUT) and focal segmental glomerular sclerosis (FSGS). (2015)
  • Author(s): Yoshimura-Furuhata M, Nishimura-Tadaki A, Amano Y, Ehara T, Hamasaki Y, Muramatsu M, Shishido S, Aikawa A, Hamada R, Ishikura K, Hataya H, Hidaka Y, Noda S, Koike K, Wakui K, Fukushima Y, Matsumoto N, Awadu M, Miyake N, Kosho T*.
  • Journal Title: Am J Med Genet Part A Volume: 167(3) Pages: 592-601
  • DOI: 10.1002/ajmg.a.36942.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] De novo SHANK3 mutation causes a female patient with Rett syndrome like phenotype. (2015)
  • Author(s): Hara M, Ohba C, Yamashita Y, Saitsu H, Matsumoto N, *Matsuishi T.
  • Journal Title: J Med Genet Part A Volume: 167(7) Pages: 1593-1596
  • DOI: 10.1002/ajmg.a.36775.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Japanese familial case of myoclonus–dystonia syndrome with a splicing mutation in the SGCE gene. (2015)
  • Author(s): *Wada T, Takano K, Tsurusaki Y, Miyake N, Nakashima M, Saitsu H, Matsumoto N, Osaka H.
  • Journal Title: Pediatr Int Volume: 57(2) Pages: 324-326
  • DOI: doi: 10.1111/ped.12613
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A family of distal arthrogryposis type 5 due to a novel PIEZO2 mutation. (2015)
  • Author(s): Okubo M#, Fujita A# (# denotes equal contribution), Saito Y, Komaki H, Ishiyama A, Kojima E, Koichihara R, Saito T, Nakagawa E, Sugai K, Yamazaki H, Kusaka K, Tanaka H, Matsumoto N, Sasaki M
  • Journal Title: Am J Med Genet Part A Volume: 167(5) Pages: 1100-1106
  • DOI: 10.1002/ajmg.a.36881
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mutations in the glutaminyl-tRNA synthetase gene cause early-onset epileptic encephalopathy. (2015)
  • Author(s): Kodera H, Osaka H, Iai M, Aida N, Yamashita A, Tsurusaki Y, Nakashima M, Miyake N, Saitsu H*, Matsumoto N* (*: co-corresponding).
  • Journal Title: J Hum Genet 60(2) Volume: 60(2) Pages: 97-101
  • DOI: 10.1038/jhg.2014.103.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Japanese girl with a severe form of vanishing white matter disease resembling Cree leukoencephalopathy. (2015)
  • Author(s): *Takano K, Tsuyusaki Y, Sato M, Takagi M, Anzai R, Okuda M, Iai M, Yamashita S, Okabe T, Aida N, Tsurusaki Y, Saitsu H, Matsumoto N, Osaka H.
  • Journal Title: Brain Dev Volume: 37(6) Pages: 638-642
  • DOI: 10.1016/j.braindev.2014.10.002.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Detecting copy number variations in whole exome sequencing data using the eXome Hidden Markov Model: an “exome-first” approach. (2015)
  • Author(s): Miyatake S, Koshimizu E, Fujita A, Fukai R, Imagawa E, Ohba C, Kuki I, Nukui M, Araki A, Makita Y, Ogata T, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, *Matsumoto N.
  • Journal Title: J Hum Genet Volume: 60(4) Pages: 175-182
  • DOI: 10.1038/jhg.2014.124.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SPTAN1 encephalopathy: distinct phenotypes and genotypes. (2015)
  • Author(s): *Tohyama J, Nakashima M, Nabatame S, Gaik-Siew C, Miyata R, Rener-Primec Z, Kato M, Matsumoto N, Saitsu H.
  • Journal Title: J Hum Genet. Volume: 60(4) Pages: 167-173
  • DOI: 10.1038/jhg.2015.5.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, hyperkinetic and stereotyped movement disorders. (2015)
  • Author(s): Ohba C, Takahashi N, Kato M, Osaka H, Takashi Shiihara T, Tohyama J, Nabatame S, Azuma J, MD, Fujii Y, MD, Hara M, Tsurusawa R, Ogata R, Watanabe Y, Togashi N, Kodera H, Nakashima M, Tsurusaki Y, Miyake N, Tanaka F, *Saitsu H, *Matsumoto N (*: co-correspondence).
  • Journal Title: Epilepsia Volume: 56(6) Pages: 841-848
  • DOI: 10.1111/epi.12987.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sporadic infantile-onset spinocerebellar ataxia caused by missense mutations of the inositol 1,4,5-triphosphate receptor type 1 gene. (2015)
  • Author(s): *Sasaki M, Ohba C, Iai M, Hirabayashi S, Osaka H, Hiraide T, Saitsu H, Matsumoto N.
  • Journal Title: J Neurol. Volume: 262(5) Pages: 1278-1284
  • DOI: 10.1007/s00415-015-7705-8.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Japanese case of cerebellar ataxia, spastic paraparesis, and deep sensory impairment associated with a novel homozygous TTC19 mutation. (2015)
  • Author(s): Kunii M, Doi H, Higashiyama Y, Kugimoto C, Ueda N, Hirata J, Tomita-Katsumoto A, Kashikura-Kojima M, Kubota S, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Matsumoto N, Tanaka F*.
  • Journal Title: J Hum Genet. Volume: 60(4) Pages: 187-191
  • DOI: 10.1038/jhg.2015.7.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A case of autism spectrum disorder arising from a de novo missense mutation in POGZ. (2015)
  • Author(s): Fukai R, Hiraki Y, Tsurusaki Y, Nakashima M, Saitsu H, *Miyake N, *Matsumoto N (*: co-corrresponding).
  • Journal Title: J Hum Genet Volume: 60(5) Pages: 277-279
  • DOI: 10.1038/jhg.2015.13.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An Aberrant Splice Acceptor Site Due to a Novel Intronic Nucleotide Substitution in MSX1 Gene Is the Cause of Congenital Tooth Agenesis in a Japanese Family. (2015)
  • Author(s): Tatematsu T, Kimura M, Nakashima M, Machida J, Yamaguchi S, Shibata A, Goto H, Nakayama A, Higashi Y, Miyachi H, Shimozato K, Matsumoto N, *Tokita Y.
  • Journal Title: Plos One Volume: 10(6) Pages: e0128227
  • DOI: 10.1371/journal.pone.0128227.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dominant mutations in ORAI1 cause tubular-aggregate- myopathy with hypocalcemia by constitutive activation of store-operated Ca2+ channel. (2015)
  • Author(s): Endo Y, *Noguchi S, Hara Y, Hayashi YK, Motomura K, Murakami N, Tanaka S, Yamashita S, Kizu R, Bamba M, Goto Y, Matsumoto N, Nonaka I, Nishino I.
  • Journal Title: Hum Mol Genet 24(3) Volume: 24(3) Pages: 637-648
  • DOI: 10.1093/hmg/ddu477.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A novel mutation in ELOVL4 leading to spinocerebellar ataxia (SCA) with the hot cross bun sign but lacking erythrokeratodermia: A broadened spectrum of SCA34. (2015)
  • Author(s): Ozaki K, Doi H, Mitsui J, Sato N, Iikuni Y, Majima T, Yamane K, Irioka T, Ishiura H, Doi K, Morishita S, Higashi M, Sekiguchi T, Koyama K, Ueda N, Miura Y, Miyatake S, Matsumoto N, Yokota T, Tanaka F, Tsuji S, Mizusawa H, *Ishikawa K.
  • Journal Title: JAMA Neurol. Volume: 72(7) Pages: 797-805
  • DOI: 10.1001/jamaneurol.2015.0610.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals. (2015)
  • Author(s): Liu X, Kawashima M, Miyagawa T, Otowa T, Latt KZ, Thiri M, Nishida H, Sugiyama T, Tsurusaki Y, Matsumoto N, Mabuchi A, Tokunaga K*, Sasaki T* (*: co-correspondence).
  • Journal Title: Human Genome Variation 2 Volume: 該当なし Pages: 15024
  • DOI: 10.1038/hgv.2015.24
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification and in vivo functional characterization of novel compound heterozygous BMP1 variants in osteogenesis imperfecta. (2015)
  • Author(s): Cho SY, Asharani PV, Kim OH, Iida A, Miyake N, Matsumoto N, Nishimura G, Ki CS, Hong G, Kim SJ, Sohn YB, Park SW, Lee J, Kwun Y, Carney TJ, Huh R, Ikegawa S#*, Jin DK#*. (*: co-correspondence) (# denotes equal contribution).
  • Journal Title: Hum Mut Volume: 36(2) Pages: 191-195
  • DOI: 10.1002/humu.22731.
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Predominant cerebellar phenotype in spastic paraplegia 7 (SPG7) (#: correspondence). (2015)
  • Author(s): Yahikozawa H, #Yoshida K, Sato S, Hanyu N, Doi H, 4, Miyatake S, Matsumoto N.
  • Journal Title: Human Genome Variation 2 Volume: 該当なし Pages: 15012
  • DOI: 10.1038/hgv.2015.12.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Somatic Mutations in the MTOR Gene Cause Focal Cortical Dysplasia Type IIb. (2015)
  • Author(s): Nakashima M, Saitsu H, Tohyama J, Kato M, Shiina M, Takei N, Kitaura H, Shirozu H, Masuda H, Watanabe K, Ohba C, Tsurusaki Y, Miyake N, Takebayashi H, Ogata K, Kameyama S, Kakita A, *Matsumoto N.
  • Journal Title: Ann Neurol Volume: 78(3) Pages: 375-386
  • DOI: 10.1002/ana.24444.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Two novel homozygous RAB3GAP1 mutations cause Warburg micro syndrome (2015)
  • Author(s): Imagawa E#, Fukai R#, Behnam M#, Goyal M# (#: equally contributed), Nouri N, Nakashima M, Tsurusaki Y, Saitsu H, Salehi M, Kapoor S, Tanaka F, *Miyake N, *Matsumoto N (*: co-correspondence).
  • Journal Title: Human Genome Variation 2 Volume: 該当なし Pages: 15034
  • DOI: 10.1038/hgv.2015.34
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Electroclinical features of epileptic encephalopathy caused by SCN8A mutation. (2015)
  • Author(s): *Takahashi S, Yamamoto S, Okayama A, Araki A, Saitsu H, Matsumoto N, Azuma H.
  • Journal Title: Pediat Int Volume: 57(4) Pages: 758-762
  • DOI: 10.1111/ped.12622.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] DNA methylation and gene expression dynamics during spermatogonial stem cell differentiation in the early postnatal testis. (2015)
  • Author(s): Kubo N, Toh H, Shirane K, Shirakawa T, Kobayashi H, Sato T, Sone H, Sato Y, Tomizawa S, Tsurusaki Y, Shibata H, Saitsu H, Suzuki Y, Matsumoto N, Suyama M, Kono T, Ohbo K, Sasak H*.
  • Journal Title: Genomics Volume: 16(1) Pages: 624
  • DOI: 10.1186/s12864-015-1833-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] De Novo 17q24.2-q24.3 microdeletion presenting with generalized hypertrichosis terminalis, gingival fibromatous hyperplasia, and distinctive facial features. (2015)
  • Author(s): Afifi H, Fukai R, Miyake N, Gamal E, Din A, Eid M, Eid O, Thomas M, El-Badry T, Tosson A, Abdel-Salam G*, Matsumoto N.
  • Journal Title: Am J Med Genet Part A Volume: 167(10) Pages: 2418-2424
  • DOI: 10.1002/ajmg.a.37185.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Biallelic mutations in NUP107 encoding a nuclear pore complex subunit cause early childhood onset steroid-Resistance nephrotic syndrome. (2015)
  • Author(s): Miyake N#, Tsukaguchi Y#, (# denotes equal contribution) Koshimizu E, Shono A, Matsunaga S, Shiina M, Mimura Y, Nozu K, Akioka Y, Hattori M, Yoshikawa N, Kitamura A, Imamura S, Yamashita M, Fijita A, Miyatake S, Tsurusaki Y, Nakashima M, Saitsu H, Imamoto N, Ryo A, Ogata K, Iijima K, *Matsumoto N (*: corresponding).
  • Journal Title: Am J Hum Genet Volume: 97(4) Pages: 555-566
  • DOI: 10.1016/j.ajhg.2015.08.013.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of HOXD4 Mutations in Spinal Extradural Arachnoid Cyst. (2015)
  • Author(s): Ogura Y, Miyake N, Kou I, Iida A, Nakajima M, Takeda K, Fujibayashi S, Shiina M, Okada E, Toyama Y, Iwanami A, Ishii K, Ogata K, Asahara H, Matsumoto N, Nakamura M, Matsumoto M, Ikegawa S*.
  • Journal Title: PLoS One. Volume: 10(11) Pages: e0142126
  • DOI: 10.1371/journal.pone.0142126.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal firing. (2015)
  • Author(s): *Saitsu H#, *Akita T# (# denotes co-first authors, *: co-correspondence), Tohyama J, Goldberg-Stern H, Kobayashi Y, Cohen R, Kato M, Ohba C, Miyatake S, Tsurusaki Y, Nakashima M, Miyake N, Fukuda A, Matsumoto N.
  • Journal Title: Sci Rep. Volume: 5 Pages: 15199
  • DOI: 10.1038/srep15199.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 「最先端テクノロジーによる疾患ゲノム解析」 (2015)
  • Author(s): 松本直通
  • Organizer: 第1回日本産婦人科遺伝診療学会学術講演会・教育講演
  • Place of Presentation: 長崎ブリックホール（長崎県長崎市）
  • Year and Date: 2015-12-18
  • Invited
• [Presentation] 「ヒト疾患とrare variants」 (2015)
  • Author(s): 松本直通
  • Organizer: 第23回食細胞機能異常症研究会、特別講演
  • Place of Presentation: 東京慈恵医科大学（東京都港区）
  • Year and Date: 2015-12-12
  • Invited
• [Presentation] “Somatic mutations in the MTOR gene cause focal cortical dysplasia type IIb” (2015)
  • Author(s): Naomichi Matsumoto
  • Organizer: Biochemistry and Molecular Biology (BMB) 2015
  • Place of Presentation: Kobe portpia hotel, Kobe. （兵庫県神戸市）
  • Year and Date: 2015-12-01
  • Int'l Joint Research / Invited
• [Presentation] “遺伝子解析におけるドロップレットディジタルPCRの活用” (2015)
  • Author(s): 松本直通
  • Organizer: 第38回日本分子生物学会年会(第88回日本生化学会大会)BMB2015, ランチョンセミナー
  • Place of Presentation: 神戸ポートピアホテル（兵庫県神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] “Rare variants in human diseases” (invited) (2015)
  • Author(s): Naomichi Matsumoto
  • Organizer: University of Split Lecture
  • Place of Presentation: University of Split, Split, Croatia.
  • Year and Date: 2015-11-09
  • Invited
• [Presentation] “Next Generation Sequencing Dissecting Human “Genetic” Diseases” (invited) (2015)
  • Author(s): Naomichi Matsumoto
  • Organizer: The VI Croatian Congress of Human Genetics
  • Place of Presentation: Hotel President Split, Split, Croatia.
  • Year and Date: 2015-11-06
  • Invited
• [Presentation] 「低頻度体細胞モザイク変異が惹起するヒト疾患」（シンポジスト） (2015)
  • Author(s): 松本直通
  • Organizer: 日本人類遺伝学会第60回大会・シンポジウム９「ヒト疾患に関わる体細胞モザイク変異とその検出法」
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-10-16
  • Invited
• [Presentation] 「遺伝性疾患における話題提供」 (2015)
  • Author(s): 松本直通
  • Organizer: 第22回日本遺伝子診療学会大会・プレシジョン医療と診断情報の質保証（シンポジウム3）
  • Place of Presentation: かながわ労働プラザ（神奈川県横浜市）
  • Year and Date: 2015-07-19
  • Invited
• [Presentation] 「ヒト疾患とrare variants」 (2015)
  • Author(s): 松本直通
  • Organizer: 第33回内分泌代謝学サマーセミナー・続・内分泌至上主義・シンポジスト（招聘）
  • Place of Presentation: 柳川藩主立花邸（福岡県柳川市）
  • Year and Date: 2015-07-09
  • Invited
• [Presentation] 「全エクソーム解析データの様々な活用法」 (2015)
  • Author(s): 松本直通
  • Organizer: 2015アジレントゲノミクスフォーラム・招聘講演
  • Place of Presentation: ヒューリックホール浅草橋（東京都台東区）
  • Year and Date: 2015-06-16
  • Invited
• [Presentation] “Deep sequencing detects very low-grade somatic mosaicism in the unaffected mother of siblings with nemaline myopathy”(poster), (2015)
  • Author(s): Naomichi Matsumoto, Eriko Koshimizu, Satoko Miyatake,
  • Organizer: European Human Genetics Conference 2015
  • Place of Presentation: Glasgow, Scotland, United Kingdom,
  • Year and Date: 2015-06-09
  • Int'l Joint Research / Invited
• [Presentation] 「遺伝性疾患の次世代シーケンス解析」 (2015)
  • Author(s): 松本直通
  • Organizer: 産総研Computational Biology Research Center (CBRC)セミナー
  • Place of Presentation: 産総研・臨海副都心センター別館（東京都江東区）
  • Year and Date: 2015-04-23
  • Invited