医科学研究センター

倉橋 浩樹

クラハシ ヒロキ  (HIROKI KURAHASHI)

基本情報

所属
藤田医科大学 医科学研究センター 分子遺伝学研究部門 教授
学位
医学博士(大阪大学)

研究者番号
30243215
J-GLOBAL ID
200901098214871015
researchmap会員ID
1000367088

外部リンク

ヒト生殖細胞系列の染色体異常(トリソミーなどの異数体、転座や欠失・重複などの構造異常)の発生メカニズムの研究をしています。また、次世代シークエンスによる着床前遺伝学的検査の開発研究を行っています。バックグラウンドは小児科医で、現在は大学病院・臨床遺伝科で、染色体異常症や不妊・習慣流産の患者さんやご家族、出生前、着床前遺伝学的検査を希望されるクライエントへの遺伝カウンセリングをおこなっています。大学院遺伝カウンセラー養成課程で人材育成も行っています。


論文

 355
  • Yuri Murase, Yui Shichiri, Hidehito Inagaki, Tatsuya Nakano, Yoshiharu Nakaoka, Yoshiharu Morimoto, Tomoko Ichikawa, Haruki Nishizawa, Eiji Sugihara, Hiroki Kurahashi
    Genes 15(8) 2024年8月21日  
    Cytogenetic information about the product of conception (POC) is important to determine the presence of recurrent chromosomal abnormalities that are an indication for preimplantation genetic testing for aneuploidy or structural rearrangements. Although microscopic examination by G-staining has long been used for such an evaluation, detection failures are relatively common with this method, due to cell-culture-related issues. The utility of low-coverage whole-genome sequencing (lcWGS) using short-read next-generation sequencing (NGS) has been highlighted recently as an alternative cytogenomic approach for POC analysis. We, here, performed comparative analysis of two NGS-based protocols for this purpose based on different short-read sequencers (the Illumina VeriSeq system using a MiSeq sequencer and the Thermo Fisher ReproSeq system using an Ion S5 sequencer). The cytogenomic diagnosis obtained with each NGS method was equivalent in each of 20 POC samples analyzed. Notably, X chromosome sequence reads were reduced in some female samples with both systems. The possibility of low-level mosaicism for monosomy X as an explanation for this was excluded by FISH analysis. Additional data from samples with various degrees of X chromosome aneuploidy suggested that it was a technical artifact related to X chromosome inactivation. Indeed, subsequent nanopore sequencing indicated that the DNA in the samples showing the artifact was predominantly unmethylated. Our current findings indicate that although X chromosome data must be interpreted with caution, both the systems we tested for NGS-based lcWGS are useful alternatives for the karyotyping of POC samples.
  • Mamiko Yamada, Seiji Mizuno, Mie Inaba, Tomoko Uehara, Hidehito Inagaki, Hisato Suzuki, Fuyuki Miya, Toshiki Takenouchi, Hiroki Kurahashi, Kenjiro Kosaki
    American journal of medical genetics. Part A e63614 2024年4月2日  
    Sonic hedgehog signaling molecule (SHH) is a key molecule in the cilia-mediated signaling pathway and a critical morphogen in embryogenesis. The association between loss-of-function variants of SHH and holoprosencephaly is well established. In mice experiments, reduced or increased signaling of SHH have been shown to be associated with narrowing or excessive expansion of the facial midline, respectively. Herein, we report two unrelated patients with de novo truncating variants of SHH presenting with hypertelorism rather than hypotelorism. The first patient was a 13-year-old girl. Her facial features included hypertelorism, strabismus, telecanthus, malocclusion, frontal bossing, and wide widow's peak. She had borderline developmental delay and agenesis of the corpus callosum. She had a nonsense variant of SHH: Chr7(GRCh38):g.155802987C > T, NM_000193.4:c.1302G > A, p.(Trp434*). The second patient was a 25-year-old girl. Her facial features included hypertelorism and wide widow's peak. She had developmental delay and agenesis of the corpus callosum. She had a frameshift variant of SHH: Chr7(GRCh38):g.155803072_155803074delCGGinsT, NM_000193.4:c.1215_1217delCCGinsA, p.(Asp405Glufs*92). The hypertelorism phenotype contrasts sharply with the prototypical hypotelorism-holoprosencephaly phenotype associated with loss-of-function of SHH. We concluded that a subset of truncating variants of SHH could be associated with hypertelorism rather than hypotelorism.
  • 中島 葉子, 安田 泰明, 須藤 湧太, 伊藤 哲哉, 倉橋 浩樹
    日本小児科学会雑誌 128(2) 281-281 2024年2月  
  • Takeshi Sugimoto, Hidehito Inagaki, Tasuku Mariya, Rie Kawamura, Mariko Taniguchi-Ikeda, Seiji Mizuno, Yukako Muramatsu, Ikuya Tsuge, Hirofumi Ohashi, Nakamichi Saito, Yuiko Hasegawa, Nobuhiko Ochi, Masatoshi Yamaguchi, Jun Murotsuki, Hiroki Kurahashi
    Human genetics 142(10) 1451-1460 2023年8月24日  
    Constitutional complex chromosomal rearrangements (CCRs) are rare cytogenetic aberrations arising in the germline via an unknown mechanism. Here we analyzed the breakpoint junctions of microscopically three-way or more complex translocations using comprehensive genomic and epigenomic analyses. All of these translocation junctions showed submicroscopic genomic complexity reminiscent of chromothripsis. The breakpoints were clustered within small genomic domains with junctions showing microhomology or microinsertions. Notably, all of the de novo cases were of paternal origin. The breakpoint distributions corresponded specifically to the ATAC-seq (assay for transposase-accessible chromatin with sequencing) read data peak of mature sperm and not to other chromatin markers or tissues. We propose that DNA breaks in CCRs may develop in an accessible region of densely packaged chromatin during post-meiotic spermiogenesis.
  • Hikari Yoshizawa, Haruki Nishizawa, Mayuko Ito, Akiko Ohwaki, Yoshiko Sakabe, Takao Sekiya, Takuma Fujii, Hiroki Kurahashi
    Fujita medical journal 9(3) 200-205 2023年8月  
    OBJECTIVES: Nectin-4 is a cell adhesion molecule with vital functions at adherens and tight junctions. Cumulative evidence now indicates that the NECTIN4 gene is overexpressed in a variety of cancers, and that the nectin-4 protein is both a disease marker and therapeutic target in a subset of these cancers. We previously demonstrated that NECTIN4 is overexpressed in placenta during pre-eclamptic pregnancy, which is one of the most serious obstetric disorders. METHODS: Nectin-4 protein levels were measured in maternal sera from pregnant women with pre-eclampsia and its related disorder, unexplained fetal growth retardation. RESULTS: Maternal serum concentrations of nectin-4 were significantly elevated in pre-eclamptic women compared with those with an uncomplicated normotensive pregnancy. However, no increase was observed in pregnancies with unexplained fetal growth retardation. Serum nectin-4 levels were higher in cases with early-onset pre-eclampsia that generally showed more severe clinical symptoms, but levels were not correlated to other clinical indicators of disease severity. CONCLUSIONS: Nectin-4 is a potential new diagnostic and predictive biomarker for severe pre-eclampsia.

MISC

 171

担当経験のある科目(授業)

 1

共同研究・競争的資金等の研究課題

 42

その他

 5
  • (1)1分子レベルでのt(11;22)(q23;q11.2)転座の検出 (2)習慣流産炉関連するANXA5プロモーター多型の解析
  • その他教育活動上特記すべき事項 藤田保健衛生大学大学院・保健学研究科・臨床検査学領域に遺伝カウンセリング分野を新規開設し、2014年度に開講した。
  • 教育方法・教育実践に関する発表、講演等 2012年〜 日本人類遺伝学会・臨床細胞遺伝学認定士制度委員として、染色体検査に携わる人材育成・知識や技術の向上などの教育に関する活動を行っている。
  • 作成した教科書、教材、参考書 2011年〜 300人規模で毎年行われる遺伝医学セミナーのテキストを作成している。
  • 教育内容・方法の工夫(授業評価等を含む) 2004年〜2005年「統合基礎医学」、2006年〜「臨床遺伝学」の講義をM2の学生に対し行い、基礎医学の講義でありながら、遺伝カウンセリングや疾患を中心とした内容でおこない、学生の評判は良かった。 2009年〜 医学研究科分子医学系専攻の大学院生のための分子生物学技術セミナーを開講 2013年〜 医学研究科大学院生のための分子生物学技術講座を開講 2014年〜 保健学研究科大学院、認定遺伝カウンセラー養成課程を開講