Establishment of new classification for structural variation based on next generation sequencing

• Project/Area Number: 15H04710
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Fujita Health University
• Principal Investigator: Kurahashi Hiroki 藤田保健衛生大学, 総合医科学研究所, 教授 (30243215)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 染色体 / ゲノム / 構造異常 / 挿入 / 端部欠失・逆位重複 / クロモスリプシス / 複雑構造異常 / 複製の停止 / 鋳型乗り換え / 遺伝子 / 遺伝学 / マイクロアレイ / 端部欠失 / 逆位重複 / FoSTeS / MMBIR

Outline of Final Research Achievements

It has been unclear how the complex structural variations arise. In this study we analyzed the genomic structure of breakpoints and junctions of complex structural variations. Microarray technique followed by next generation sequencing revealed the genomic information of the breakpoints and junctions. Chromosomal insertions carry complex alternation of the copy number states, suggesting that chromothripsis occurred. Difference of the DNA replication between nuclear genome and chromosome in micronucleus derived from lagging chromosome might lead to the DNA shuttering that might induce the chromothripsis.

Research Products

• [Int'l Joint Research] Newcastle University(英国)
• [Int'l Joint Research] Cornell University(米国)
• [Int'l Joint Research] Newcastle University(英国)
• [Int'l Joint Research] Cornell University(米国)
• [Journal Article] Multiplex PCR in noninvasive prenatal diagnosis for FGFR3-related disorders (2018)
  • Author(s): Terasawa Sumire、Kato Asuka、Nishizawa Haruki、Kato Takema、Yoshizawa Hikari、Noda Yoshiteru、Miyazaki Jun、Ito Mayuko、Sekiya Takao、Fujii Takuma、Kurahashi Hiroki
  • Journal Title: Congenital Anomalies Volume: - Issue: 1 Pages: 1-7
  • DOI: 10.1111/cga.12278
  • Peer Reviewed / Open Access
• [Journal Article] PCS/MVA syndrome caused by an Alu insertion in the BUB1B gene (2017)
  • Author(s): Kato Maki、Kato Takema、Hosoba Eriko、Ohashi Masanao、Fujisaki Midori、Ozaki Mamoru、Yamaguchi Masatoshi、Sameshima Hiroshi、Kurahashi Hiroki
  • Journal Title: Human Genome Variation Volume: 4 Issue: 1 Pages: 17021-17021
  • DOI: 10.1038/hgv.2017.21
  • Peer Reviewed / Open Access
• [Journal Article] Novel missense mutation in DLL4 in a Japanese sporadic case of Adams-Oliver syndrome (2017)
  • Author(s): Nagasaka M, Taniguchi-Ikeda M, Inagaki H, Ouchi Y, Kurokawa D, Yamana K, Harada R, Nozu K, Sakai Y, Mishra SK, Yamaguchi Y, Morikoka I, Toda T, Kurahashi H, Iijima K
  • Journal Title: J Hum Genet Volume: 62 Issue: 9 Pages: 869-869
  • DOI: 10.1038/jhg.2017.59
  • Peer Reviewed
• [Journal Article] A case with concurrent duplication, triplication, and uniparental isodisomy at 1q42.12-qter supporting microhomology-mediated break-induced replication model for replicative rearrangements (2017)
  • Author(s): Kohmoto T, Okamoto N, Naruto T, Murata C, Ouchi Y, Fujita N, Inagaki H, Satomura S, Okamoto N, Saito M, Masuda K, Kurahashi H, Imoto I
  • Journal Title: Mol Cytogenet Volume: 10 Issue: 1 Pages: 15-15
  • DOI: 10.1186/s13039-017-0316-6
  • NAID: 120006937633
  • Peer Reviewed / Open Access
• [Journal Article] Intragenic DOK7 deletion detected by whole-genome sequencing in congenital myasthenic syndromes. (2017)
  • Author(s): Azuma Y, Topf A, Evangelista T, Lorenzoni PJ, Roos A, Viana P, Inagaki H, Kurahashi H, Lochmuller H
  • Journal Title: Neurol Genet Volume: 3 Issue: 3
  • DOI: 10.1212/nxg.0000000000000152
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Analysis of the origin of inherited chromosomally integrated human herpesvirus 6 in the Japanese population. (2017)
  • Author(s): Kawamura Y, Ohye T, Miura H, Ihira M, Kato Y, Kurahashi H, Yoshikawa T.
  • Journal Title: J Gen Virol. Volume: 98(7) Issue: 7 Pages: 1823-1830
  • DOI: 10.1099/jgv.0.000834
  • Peer Reviewed / Open Access
• [Journal Article] The DNA Damage Checkpoint Eliminates Mouse Oocytes with Chromosome Synapsis Failure (2017)
  • Author(s): Vera Rinaldi, Ewelina Bolcun-Filas, Hiroshi Kogo, Hiroki Kurahashi, John C.Schimenti
  • Journal Title: Molecular Cell Volume: 67 Issue: 6 Pages: 1026-1036.e2
  • DOI: 10.1016/j.molcel.2017.07.027
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Remote intracranial recurrence of <i>IDH</i> mutant gliomas is associated with <i>TP53</i> mutations and an 8q gain (2017)
  • Author(s): Nakae Shunsuke、Kato Takema、Murayama Kazuhiro、Sasaki Hikaru、Abe Masato、Kumon Masanobu、Kumai Tadashi、Yamashiro Kei、Inamasu Joji、Hasegawa Mitsuhiro、Kurahashi Hiroki、Hirose Yuichi
  • Journal Title: Oncotarget Volume: 8 Issue: 49 Pages: 84729-84742
  • DOI: 10.18632/oncotarget.20951
  • Peer Reviewed / Open Access
• [Journal Article] Genomic Characterization of Chromosomal Insertions: Insights into the Mechanisms Underlying Chromothripsis (2017)
  • Author(s): Kato Takema、Ouchi Yuya、Inagaki Hidehito、Makita Yoshio、Mizuno Seiji、Kajita Mitsuharu、Ikeda Toshiro、Takeuchi Kazuhiro、Kurahashi Hiroki
  • Journal Title: Cytogenetic and Genome Research Volume: 153 Issue: 1 Pages: 1-9
  • DOI: 10.1159/000481586
  • Peer Reviewed / Open Access
• [Journal Article] PCS/MVA syndrome caused by an Alu insertion in the BUB1B gene. (2017)
  • Author(s): Kato M, Kato T, Hosoba E, Ohashi M, Fujisaki M, Ozaki M, Yamaguchi M, Sameshima H, *Kurahashi H.
  • Journal Title: Hum Genome Var Volume: 印刷中
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Family With Craniofrontonasal Syndrome: The First Report of Familial Cases of Craniofrontonasal Syndrome With Bilateral Cleft Lip and Palate. (2017)
  • Author(s): Inoue Y, Sakamoto Y, Sugimoto M, Inagaki H, Boda H, Miyata M, Kato H, Kurahashi H, *Okumoto T.
  • Journal Title: Cleft Palate Craniofac J Volume: 印刷中 Issue: 7 Pages: 15347-15347
  • DOI: 10.1597/15-347
  • Peer Reviewed
• [Journal Article] Palindrome-mediated translocations in humans: a new mechanistic model for gross chromosomal rearrangements. (2016)
  • Author(s): Inagaki H, Kato T, Tsutsumi M, Ouchi Y, Ohye T, *Kurahashi H.
  • Journal Title: Front Genet Volume: 7 Pages: 125-125
  • DOI: 10.3389/fgene.2016.00125
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel compound heterozygous variants in PLK4 identified in a patient with autosomal recessive microcephaly and chorioretinopathy. (2016)
  • Author(s): Tsutsumi M, Yokoi S, Miya F, Miyata M, Kato M, Okamoto N, Tsunoda T, Yamasaki M, Kanemura Y, Kosaki K, Saitoh S, *Kurahashi H.
  • Journal Title: Eur J Hum Genet Volume: 24 Issue: 12 Pages: 1702-1706
  • DOI: 10.1038/ejhg.2016.119
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A PDE3A mutation in familial hypertension and brachydactyly syndrome (2016)
  • Author(s): Boda H, Uchida H, Takaiso N, Ouchi Y, Fujita N, Kuno A, Hata T, et al.
  • Journal Title: J Hum Gene Volume: Apr 7 Issue: 8 Pages: 1-6
  • DOI: 10.1038/jhg.2016.32
  • NAID: 40020923782
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Next-generation sequencing discloses a nonsense mutation in the dystrophin gene from long preserved dried umbilical cord and low-level somatic mosaicism in the proband mother. (2016)
  • Author(s): Taniguchi-Ikeda M, Takeshima Y, Lee T, Nishiyama M, Awano H, Yagi M, Unzaki A, Nozu K, Nishio H, Matsuo M, Kurahashi H, Toda T, Morioka I, Iijima K.
  • Journal Title: J Hum Genet. Volume: 61 Issue: 4 Pages: 351-355
  • DOI: 10.1038/jhg.2015.157
  • NAID: 40020802923
  • Peer Reviewed / Open Access
• [Journal Article] Annexin A5 haplotype M2 is not a risk factor for recurrent miscarriages in Northern Europe, is there sufficient evidence? (2016)
  • Author(s): *Markoff A, Kurahashi H, Grandone E, Bogdanova N.
  • Journal Title: Reprod Biomed Online Volume: 32 Issue: 5 Pages: 469-73
  • DOI: 10.1016/j.rbmo.2016.02.004
  • Peer Reviewed
• [Journal Article] Authors' response to the letter of Nagirnaja et al., "Response to annexin A5 haplotype M2 is not a risk factor for recurrent miscarriages in Northern Europe, is there sufficient evidence?" (2016)
  • Author(s): Markoff A, Kurahashi H, Grandone E, Bogdanova N.
  • Journal Title: Reprod Biomed Online Volume: 33 Issue: 1 Pages: 116-7
  • DOI: 10.1016/j.rbmo.2016.05.006
  • Peer Reviewed
• [Journal Article] A simple cytogenetic method to detect chromosomally integrated human herpesvirus-6. (2016)
  • Author(s): Ohye T, et al.
  • Journal Title: J Virol Methods Volume: 228 Pages: 74-78
  • DOI: 10.1016/j.jviromet.2015.11.001
  • Peer Reviewed / Open Access
• [Journal Article] Complex X-Chromosomal Rearrangements in Two Women with Ovarian Dysfunction: Implications of Chromothripsis/Chromoanasynthesis-Dependent and -Independent Origins of Complex Genomic Alterations. (2016)
  • Author(s): Suzuki E, Shima H, Toki M, Hanew K, Matsubara K, Kurahashi H, Narumi S, Ogata T, Kamimaki T, *Fukami M.
  • Journal Title: Cytogenet Genome Res Volume: 150 Issue: 2 Pages: 86-92
  • DOI: 10.1159/000455026
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increased levels of soluble corin in pre-eclampsia and fetal growth restriction. (2016)
  • Author(s): Miyazaki J, *Nishizawa H, Kambayashi A, Ito M, Noda Y, Terasawa S, Kato T, Miyamura H, Shiogama K, Sekiya T, Kurahashi H, Fujii T.
  • Journal Title: Placenta Volume: 48 Pages: 20-25
  • DOI: 10.1016/j.placenta.2016.10.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Successful living donor liver transplantation for classical maple syrup urine disease. (2016)
  • Author(s): Yasui T, Suzuki T, Hara F, Watanabe S, Uga N, Naoe A, Yoshikawa T, Ito T, Nakajima Y, Miura H, Sugioka A, Kato Y, Tokoro T, Tanahashi Y, Kasahara M, Fukuda A, Kurahashi H. Successful living donor liver transplantation for classical maple syrup urine disease.
  • Journal Title: Pediatr Transplant Volume: 20 Issue: 5 Pages: 707-710
  • DOI: 10.1111/petr.12738
  • Peer Reviewed
• [Journal Article] Mutation analysis of the JUNO gene in female infertility of unknown etiology. (2016)
  • Author(s): Takaiso N, Nishizawa H, Nishiyama S, Sawada T, Hosoba E, Ohye T, Sato T, Inagaki H, *Kurahashi H.
  • Journal Title: Fujita Med J Volume: 2 Pages: 59-61
  • NAID: 130005264393
  • Peer Reviewed
• [Presentation] Recent advance in our understanding of the molecular nature of chromosomal abnormalities (2017)
  • Author(s): 倉橋浩樹
  • Organizer: 日本人類遺伝学会第62回大会
  • Invited
• [Presentation] Screening for Genetic Disease within the Asian Context (2017)
  • Author(s): Hiroki Kurahashi
  • Organizer: ASPIRE 3rd Masterclass
  • Int'l Joint Research / Invited
• [Presentation] 次世代型PGD/PGSの現状と問題点 (2017)
  • Author(s): 倉橋浩樹
  • Organizer: 第62回日本生殖医学会学術講演会
  • Invited
• [Presentation] 造血器腫瘍のクリニカルシーケンスにおける遺伝診療体制の構築 (2017)
  • Author(s): 倉橋浩樹
  • Organizer: 第５９回日本小児血液・がん学会学術集会
  • Invited
• [Presentation] 網羅的手法による次世代型PGD ～PGDの実際とこれから (2017)
  • Author(s): 倉橋浩樹
  • Organizer: JISARTシンポジウム
  • Invited
• [Presentation] 着床前診断の現状と今後の展望 (2017)
  • Author(s): 倉橋浩樹
  • Organizer: 第19回日本イアンドナルド超音波講座
  • Invited
• [Presentation] 造血器腫瘍のクリニカルシーケンスにおける遺伝診療体制の構築 (2017)
  • Author(s): 倉橋浩樹
  • Organizer: 第59回日本小児血液・がん学会学術集会
  • Invited
• [Presentation] 網羅的手法による次世代型PGD ~PGDの実際とこれから (2017)
  • Author(s): 倉橋浩樹
  • Organizer: JISARTシンポジウム
  • Invited
• [Presentation] Gene expression analysis reveals molecular phenotypes related to schizophrenia in Neurogranin knockout mice. (2016)
  • Author(s): Hattori S, Hagihara H, Kameyama T, Ouchi Y, Inagaki H, Kurahashi H, Huang FL, Huang KP, Miyakawa T.
  • Organizer: Neuroscience 2016
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Missense mutations in the PLK4 gene identified in a patient with autosomal recessive microcephaly and chorioretinopathy. (2016)
  • Author(s): Tsutsumi M, Yokoi S, Miya F, Miyata M, Kato M, Okamoto N, Tsunoda T, Yamasaki M, Kanemura Y, Kosaki K, Saitoh S, Kurahashi H.
  • Organizer: ASHG2016
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] Mechanistic analysis and prediction of interchromosomal insertional translocation. (2016)
  • Author(s): Kato T, Ouchi Y, Inagaki H, Makita Y, Mizuno S, Kurahashi H.
  • Organizer: ASHG2016
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] 13q22.2q34 tetrasomy mosaicism due to an inverted duplication with a neocentromere. (2016)
  • Author(s): Hattori T, Togawa T, Togawa Y, Kawabe H, Kato T, Kurahashi H, Saitoh S, Kouwaki M, Koyama N.
  • Organizer: ASHG2016
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] Relationship between various clinical features in a genotyped population investigated for tuberous sclerosis complex. (2016)
  • Author(s): Ishihara N, Sasaki H, Kato T, Inagaki H, Tsutsumi M, Shiroki R, Kurahashi H.
  • Organizer: ASHG2016
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] De novo translocation frequency of the recurrent constitutional t(11;22)(q23;q11.2) in normal somatic tissues. (2016)
  • Author(s): Kurahashi H, Kato T, Suzuki M, Tsutsumi M, Ohye T, Inagaki H.
  • Organizer: ESHG2016
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2016-05-21
  • Int'l Joint Research
• [Presentation] Palindrome-mediated recurrent translocations in humans. (2016)
  • Author(s): Kurahashi H.
  • Organizer: ICHG2016
  • Place of Presentation: Kyoto, Japan、京都国際会館
  • Year and Date: 2016-04-03
  • Int'l Joint Research / Invited
• [Presentation] Mechanisms of interchromosomal insertional translocation. (2016)
  • Author(s): Kato T, Ouchi Y, Inagaki H, Makita Y, Mizuno S, Kurahashi H.
  • Organizer: ICHG2016
  • Place of Presentation: Kyoto, Japan、京都国際会館
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] A PDE3A mutation in familial hypertension and brachydactyly syndrome. (2016)
  • Author(s): Inagaki H, Boda H, Uchida H, Takaiso N, Ouchi Y, Fujita N, Kuno A, Hata T, Nagatani A, Funamoto Y, Miyata M, Yoshikawa T, Kurahashi H.
  • Organizer: ICHG2016
  • Place of Presentation: Kyoto, Japan、京都国際会館
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Spermatogenic failure by impaired meiotic sex chromosome inactivation in a mouse with reciprocal translocation. (2016)
  • Author(s): Tsutsumi M, Kato T, Inagaki H, Ohye T, Kurahashi H.
  • Organizer: ICHG2016
  • Place of Presentation: Kyoto, Japan、京都国際会館
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Cell culture model for X-linked disorder: craniofrontonasal dysplasia and severe phenotype in female. (2016)
  • Author(s): Sugimoto M, Inagaki H, Tsutsumi M, Inoue Y, Taguchi Y, Boda H, Miyata M, Okumoto T, Yoshikawa T, Kurahashi H.
  • Organizer: ICHG2016
  • Place of Presentation: Kyoto, Japan、京都国際会館
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] A child presenting distinct phenotype in severe alternating hemiplegia with a novel ATP1A3 mutation. (2016)
  • Author(s): Ishihara N, Inagaki H, Miyake M, Ouchi Y, Ohye T, Tsutsumi M, Yoshikawa T, Kurahashi H.
  • Organizer: ICHG2016
  • Place of Presentation: Kyoto, Japan、京都国際会館
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Sex determination of the fetus by noninvasive prenatal testing (NIPT) with maternal blood. (2016)
  • Author(s): Noda Y, Nishizawa H, Kato T, Kambayashi A, Terasawa S, Miyazaki J, Ito M, Kurahashi H, Fujii T.
  • Organizer: ICHG2016
  • Place of Presentation: Kyoto, Japan、京都国際会館
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Increased levels of soluble corin in patients with pre-eclampsia and fetal growth restriction. (2016)
  • Author(s): Miyazaki J, Nishizawa H, Kambayashi A, Ito M, Noda Y, Terasawa S, Kato T, Miyamura H, Sekiya T, Kurahashi H, Fujii T.
  • Organizer: ICHG2016
  • Place of Presentation: Kyoto, Japan、京都国際会館
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Advantage of next generation sequencing in molecular diagnosis in DMD -mutation screening with long preserved dried umbilical cord and detection of mosaicism-. (2016)
  • Author(s): Unzaki A, Taniguchi-Ikeda M, Takeshima Y, Lee T, Awano H, Yagi M, Kurahashi H, Morioka I, Toda T, Matsuo M, Iijima K.
  • Organizer: ICHG2016
  • Place of Presentation: Kyoto, Japan、京都国際会館
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Prenatal diagnosis of the Premature chromosome separation/ mosaic variegated aneuploidy (PCS/MVA) syndrome in fetus with microcephalus. (2016)
  • Author(s): Ohashi M, Yamaguchi M, Ishii M, Yamaguchi T, Akeno K, Fijisaki M, Sumiyoshi C, Sameshima H, Ozaki M, Kato T, Inagaki H, Kurahashi H.
  • Organizer: ICHG2016
  • Place of Presentation: Kyoto, Japan、京都国際会館
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Mechanism for Structural Variation. (2016)
  • Author(s): Kurahashi H.
  • Organizer: APAC RGH Symposium Singapore
  • Place of Presentation: Singapore
  • Int'l Joint Research / Invited
• [Remarks] 藤田保健衛生大学・総合医科学研究所・分子遺伝学研究部門
  • URL: http://molgen.icms.fujita-hu.ac.jp
• [Remarks] ようこそ分子遺伝学研究室へ
  • URL: http://molgen.icms.fujita-hu.ac.jp