Development of personalized diagnosis systems using combination of a supporting program for clinical diagnosis of genetic diseases with HRM analysis for molecular diagnosis

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591506
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: University of the Ryukyus
• Principal Investigator: NARITOMI Kenji 琉球大学, 医学(系)研究科(研究院), 教授 (20101446)
• Co-Investigator(Renkei-kenkyūsha): KANAME Tadashi 琉球大学, 大学院医学研究科, 准教授 (40264288) ; YANAGI Kumiko 琉球大学, 大学院医学研究科, 助教 (90294701)
• Project Period (FY): 2011 – 2013
• Keywords: 診断用ソフトウェア / 奇形症候群 / 遺伝子 / 高精度融解曲線分析法

Research Abstract

Database for genetic diseases and supporting program for the diagnosis (UR-DBMS, Syndrome Finder) were developed and renewed year-on-year. The database including responsible genes for the diseases was published to the web site (http://becomerich.lab.u-ryuyu.ac.jp/).
In addition to the published database, we constructed mutation-screening plates for the genes, FGD1, MLL2, CD96, ASXL1, or genes for autism spectrum disorders to substantialize the system for personal molecular diagnosis in combination with the supporting program.

Research Products

• [Journal Article] A commentary on the promise of whole-exome sequencing in medical genetics (2014)
  • Author(s): Kaname T, Yanagi K, Naritomi K.
  • Journal Title: Journal of Human Genetics Volume: 59 Pages: 117-118
  • DOI: 10.1038/jhg2014.7
  • Peer Reviewed
• [Journal Article] Prenatal diagnosis of X-linked recessive Lenz microphthalmia syndrome (2013)
  • Author(s): Suzumori N, Kaname T, Muramatsu Y, Yanagi K, Kumagai K, Mizuno S, Naritomi K, Saitho S, Sugiura M.
  • Journal Title: Journal of Obstetrics and Gynecology Research Volume: 39 Pages: 1545-1547
  • DOI: 10.1111/jog.12081
  • Peer Reviewed
• [Journal Article] Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome (2013)
  • Author(s): Ganaha A, Kaname T, Yanagi K, Naritomi K, Tono T, Usami S, Suzuki M.
  • Journal Title: BMC Medical Genetisc Volume: 14 Pages: 56
  • DOI: 10.1186/1471-2350-14-56
  • Peer Reviewed
• [Journal Article] Clinical correlations of mutations affecting six components of the SWI/SNF complex : detailed description of 21 patients and a review of the literature (2013)
  • Author(s): Kosho T, Okamoto N, Ohashi H, Tsurusaki Y, Imai Y, Hibi-Ko Y, Kawame H, Homma T, Tanabe S, Kato M, Hiraki Y, Yamagata T, Yano S, Sakazume S, Ishii T, Nagai T, Ohta T, Niikawa N, Mizuno S, Kaname T, Naritomi K, Narumi Y, Wakui K, Fukushima Y, Miyatake S, Mizuguchi T, Saitsu H, Miyake N, Matsumoto N.
  • Journal Title: Am J Med Genet Volume: 161A Pages: 1221-1237
  • DOI: 10.1002/ajmg.a.35933
  • Peer Reviewed
• [Journal Article] In memoriam of Shozo Ohdo MD,PhD : one of the pioneers of clinical geneticist in Japan (2013)
  • Author(s): Naritomi K.
  • Journal Title: J Hum Genet Volume: 58 Pages: 117
  • DOI: 10.1038/jhg.2012.150
  • Peer Reviewed
• [Journal Article] A commentary on the diagnostic utility of exome sequencing in Joubert syndrome and related disorders (2013)
  • Author(s): Kaname T, Yanagi K, Naritomi K.
  • Journal Title: J Hum Genet Volume: 58 Pages: 57
  • DOI: 10.1038/jhg.2012.138
  • Peer Reviewed
• [Journal Article] The history of human populations in the Japanese Archipelago inferred from genomewide SNP data with a special reference to the Ainu and the Ryukyuan populations (2012)
  • Author(s): Jinam T, Nishida N, Hirai M, Kawamura S, OOta H, Umetsu K, Kimura R, Ohashi J, Tajima A, Yamamoto T, Tanabe H, Mano S, Suto Y, Kaname T, Naritomi K, Yanagi K, Niikawa N, Omoto K, Tokunaga K, Saitou N.
  • Journal Title: J Hum Genet Volume: 57 Pages: 787-795
  • DOI: 10.1038/jhg.2012.114
  • Peer Reviewed
• [Journal Article] Identification of four novel synonymous substitutions in the X-linked genes neuroligin 3 and neuroligin 4X in Japanese patients with autistic spectrum disorder (2012)
  • Author(s): Yanagi K, Kaname T, Wakui K, Hashimoto O, Fukushima Y, Naritomi K.
  • Journal Title: Autism Res Treat Volume: id724072
  • DOI: 10.1155/2012/724072
  • Peer Reviewed
• [Journal Article] Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome (2012)
  • Author(s): Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, Kaname T, Naritomi K, Kawame H, Wakui K, Fukushima Y, Homma T, Kato M, Hiraki Y, Yamagata T, Yano S, Mizuno S, Sakazume S, Ishii T, Nagai T, Shiina M, Ogata K, Ohta T, Niikawa N, Miyatake S, Okada I, Mizuguchi T, Doi H, Saitsu H, Miyake N, Matsumoto N.
  • Journal Title: Nat Genet Volume: 44(4) Pages: 376-378
  • DOI: 10.1038/ng.2219
  • Peer Reviewed
• [Journal Article] Paleolithic Contingent in Modern Japanese (2012)
  • Author(s): He Y, Wang WR, Xu S, Jin L, Pan-Asia SNP Consortium (Naritomi K)
  • Journal Title: Estimation and Inference using Genome-wide Data. Sci Rep Volume: 2 Pages: 355
  • DOI: 10.1038/srep00355
  • Peer Reviewed
• [Journal Article] Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos-like features (2012)
  • Author(s): Yoneda Y, Saitsu H, Touyama M, Makita Y, Miyamoto A, Hamada K, Kurotaki N, Tomita H, Nishiyama K, Tsurusaki Y, Doi H, Miyake N, Ogata K, Naritomi K, Matsumoto N.
  • Journal Title: J Hum Genet Volume: 57 Pages: 207-211
  • DOI: 10.1038/jhg.2012.7
  • Peer Reviewed
• [Journal Article] Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome (2011)
  • Author(s): Hannibal MC, Buckingham KJ, Ng SB, Ming JE, Beck AE, McMillin MJ, Gildersleeve HI, Bigham AW, Tabor HK, Mefford HC, Cook J, Yoshiura K-i, Matsumoto T, Matsumoto N, Miyake N, Tonoki H, Naritomi K, Kaname T, Nagai T, Ohashi H, Kurosawa K, Hou J-W, Ohta T, Liang D, Sudo A, Morris CA, Banka S, Black GC, Clayton-Smith J, Nickerson DA, Zackai EH, Shaikh TH, Donnai D, Niikawa N, Shendure J, Bamshad MJ.
  • Journal Title: Am J Med Genet Volume: 155A Pages: 1511-1516
  • DOI: 10.1002/ajmg.a.34074
  • Peer Reviewed
• [Journal Article] Population genetic structure of peninsular Malaysia Malay sub-ethnic groups (2011)
  • Author(s): Hatin WI, Nur-Shafawati AR, Zahri MK, Xu S, Jin L, Tan SG, Rizman-Idid M, Zilfalil BA; HUGO Pan-Asian SNP Consortium (Naritomi K).
  • Journal Title: PLoS One Volume: 6 Pages: e18312
  • DOI: 10.1371/journal.pone.0018312
  • Peer Reviewed
• [Presentation] Detection and estimation of variations and their frequencies in a targeted genomic region in a specific population by NGS analysis using pooled DNAs (2013)
  • Author(s): T. Kaname, K. Yanagi, M. Higa, A. Ganaha, K. Teruya, K. Sato, T. Hirano, Naritomi K.
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド,神戸
  • Year and Date: 20131203-06
• [Presentation] 疾患を対象とした可変追加型遺伝子診断パネルの作製と実践(Craniosynostosis, collagenopathy 220) (2013)
  • Author(s): 要匡、柳久美子、比嘉真紀、知念安紹、當間隆也、泉川良範、新川詔夫、吉浦孝一郎、成富研二
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 江陽グランドホテル,仙台
  • Year and Date: 20131121-23
• [Presentation] Detection of variations and their frequencies of the CCR5 gene and its promoter region in Japanese and Okinawan population by NGS analysis using pooled DNAs Authors (2013)
  • Author(s): T. Kaname, K. Yanagi, M. Higa, S. Song, Naritomi K
  • Organizer: The American Society of Human Genetics, 63rd Annual Meeting
  • Place of Presentation: Boston, MT, USA
  • Year and Date: 20131022-26
• [Presentation] Identificatbn of two novel mutations in the NOG gene in potients with Symphalangism syndrome. Authors (2013)
  • Author(s): A. Ganaha, T. Kaname, K. Yanagi, K. Naritomi, M. Suzuki
  • Organizer: EUROPEAN Human Genetics CONFERENCE 2013
  • Place of Presentation: Paris, France
  • Year and Date: 20130608-11
• [Presentation] FGD1遺伝子変異を認めるAarskog-Scott症候群の特徴 (2013)
  • Author(s): 要匡、岡本伸彦、黒澤健司、泉川良範、福嶋義光、水野誠司、成富研二
  • Organizer: 第116回日本小児科学会学術集会
  • Place of Presentation: 広島国際会議場,広島市文化交流会館;広島
  • Year and Date: 20130419-21
• [Presentation] Expression and cellular localization of the Trk-fused gene (TFG) (2012)
  • Author(s): K. Yanagi, T. Kaname, Y. Sakiyama, H. Takashima, K. Naritomi
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場,福岡
  • Year and Date: 20121211-14
• [Presentation] Novel mutations of the FGD1 gene in 16 patients with Aarskog-Scott syndrome (2012)
  • Author(s): T. Kaname, K. Yanagi, N. Okamoto, K. Kurosawa, Y. Izumikawa, Y. Fukushima, Y. Makita, M. Tsukahara, A. Altincik, S. Mizuno, K. Naritomi
  • Organizer: The American Society of Human Genetics, 62nd Annual Meeting
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 20121106-10
• [Presentation] G-band染色により核型46,XY,der(3)der(7), inv ins(3;7) (q21;q32q21.1)とされた裂手裂足患児の転座切断点解析 (2012)
  • Author(s): 柳久美子、要匡、小口良子、當間隆也、泉川良範、吉浦孝一郎、新川詔夫、成富研二
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 京王プラザホテル,東京
  • Year and Date: 20121025-27
• [Presentation] Aarskog-Scott症候群におけるFGD1遺伝子変異解析 (2012)
  • Author(s): 要匡、柳久美子、岡本伸彦、黒澤健司、泉川良範、福嶋義光、蒔田芳男、近藤郁子、塚原正人、Ayca Altincik、水野誠司、伊藤靖典、成富研二
  • Organizer: 第19回日本遺伝子診療学会
  • Place of Presentation: 三井ガーデンホテル千葉;千葉
  • Year and Date: 20120727-28
• [Presentation] Bohring-Opitz症候群およびOpitz C症候群における遺伝子変異 (2012)
  • Author(s): 要匡、柳久美子、福嶋義光、蒔田芳男、水野誠司、吉浦孝一郎、新川詔夫、成富研二
  • Organizer: 第52回日本先天異常学会学術集会
  • Place of Presentation: 東京女子医科大学弥生記念講堂;東京
  • Year and Date: 20120706-08
• [Presentation] Distinct pathogenic substitution of IVS15+5G>A in the SLC26A4 gene in patients with enlarged vestibular aqueduct and Pendred syndrome in Okinawa islands (2012)
  • Author(s): A. Ganaha, T. Kaname, K. Yanagi, K. Naritomi, S. Usami, M. Suzuki
  • Organizer: EUROPEAN Human Genetics CONFERENCE 2012
  • Place of Presentation: Nürnberg, Germany
  • Year and Date: 20120623-26
• [Presentation] 次世代シーケンサによるレンツ小眼球症候群の変異同定と診断システムの確立 (2012)
  • Author(s): 要匡、當間隆也、村松友佳子、板垣裕輔、水野誠司、黒澤健司、成富研二
  • Organizer: 第115回日本小児科学会学術集会
  • Place of Presentation: 福岡国際会議場;福岡
  • Year and Date: 20120420-22
• [Presentation] Screening of mutations in the FGD1 gene in Japanese patients with Aarskog-Scott syndrome (2011)
  • Author(s): K. Yanagi, T. Kaname, K. Naritomi
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜,横浜
  • Year and Date: 20111213-16
• [Presentation] Opitz C様症候群(Bohring-Opitz症候群)におけるASXL1遺伝子変異 (2011)
  • Author(s): 要匡、柳久美子、福嶋義光、水野誠司、吉浦孝一郎、新川詔夫、成富研二
  • Organizer: 日本人類遺伝学会第56回大会
  • Place of Presentation: 幕張メッセ,千葉
  • Year and Date: 20111110-12
• [Presentation] Aarskog-Scott症候群におけるFGD1遺伝子変異 (2011)
  • Author(s): 柳久美子、要匡、岡本伸彦、塚原正人、黒澤健司、泉川良範、福嶋義光、蒔田芳男、近藤郁子、Ayca Altincik、水野誠司、伊藤靖典、成富研二
  • Organizer: 日本人類遺伝学会第56回大会
  • Place of Presentation: 幕張メッセ,千葉
  • Year and Date: 20111110-12
• [Presentation] Detection of a mutation in Lenz microphthalmia family by exome sequencing (2011)
  • Author(s): T. Kaname, K. Yanagi, Y. Muramatsu, T. Tohma, H. Hanafusa, K. Morita, S. Ikematsu, Y. Itagaki, K. Kurosawa, S. Mizuno, K. Yoshiura, K. Naritomi
  • Organizer: The American Society of Human Genetics, 60th Annual Meeting Montreal
  • Place of Presentation: Quebec, Canada
  • Year and Date: 20111011-15
• [Presentation] 免疫グロブリンスーパーファミリーCD96の細胞外マトリックスタンパク質との反応性の検討 (2011)
  • Author(s): 要匡、柳久美子、森田この美、池松真也、成富研二
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都国際会館;京都
  • Year and Date: 20110921-24
• [Presentation] Opitz三角頭蓋症候群原因遺伝子CD96のPCR—HRM法による変異スキャニングシステム (2011)
  • Author(s): 要匡、森田この美、柳久美子、花房宏昭、吉浦孝一郎、池松真也、成富研二
  • Organizer: 第51回日本先天異常学会学術集会
  • Place of Presentation: シェーンバッハ・サボー;東京
  • Year and Date: 20110722-24
• [Presentation] Lenz小眼球症候群を呈する一家系の原因遺伝子解析 (2011)
  • Author(s): 要匡、柳久美子、當間隆也、村松友佳子、森田この美、池松真也、板垣裕輔、水野誠司、吉浦孝一郎、成富研二
  • Organizer: 第18回出生前診断研究会
  • Place of Presentation: 佐賀大医学部臨床大講堂;佐賀
  • Year and Date: 2011-10-01
• [Remarks]
  • URL: http://becomerich.lab.u-ryukyu.ac.jp/