Elucidation of the pathogenic mechanism and the clinical spectrum of disorders associated with imprinted genes on human chromosome 14

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390101
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: KAGAMI Masayo National Research Institute for Child Health and Development, 分子内分泌研究部, 上級研究員 (70399484)
• Co-Investigator(Kenkyū-buntansha): OGATA Tsutomu 独立行政法人国立成育医療研究センター, 分子内分泌研究部, 部長 (40169173) ; YAMAZAWA Kazuki 独立行政法人国立成育医療研究センター, 分子内分泌研究部, 共同研究員 (10338113) ; TAKADA Shuji 独立行政法人国立成育医療研究センター, システム発生・再生医学研究部, 室長 (20382856)
• Project Period (FY): 2008 – 2010
• Keywords: インプリンティング / エピジェネティクス / 成長障害 / 胎盤 / 臨床像 / 遺伝子調節

Research Abstract

We identified two 14q32.2 imprinting centers in the body and the placenta, respectively. The germline-derived primary DLK1-MEG3 intergenic differentially methylated region (IG-DMR) acts as an upstream regulator for the methylation pattern of the postfertilization-derived secondary MEG3-DMR in the body but not in the placenta, and that the IG-DMR and the MEG3-DMR function as imprinting control centers in the placenta and the body, respectively. This is the first study demonstrating an essential long-range imprinting regulatory function for the secondary DMR.

Research Products

• [Journal Article] Radiological evaluation of dysmorphic thorax of paternal uniparental disomy 14. (2011)
  • Author(s): Miyazaki O, Nishimura G, Kagami M, Ogata T.
  • Journal Title: Pediatric Radiology. Epub ahead of print
  • Peer Reviewed
• [Journal Article] Prenatal findings of paternal uniparental disomy 14 : Delineation of further patient. (2010)
  • Author(s): Suzumori N, Ogata T, Mizutani E, Hattori Y, Matsubara K, Kagami M, Sugiura-Ogasawara M.
  • Journal Title: American Journal Medical Genetics A. 152A(12) Pages: 3189-3192
  • Peer Reviewed
• [Journal Article] The IG-DMR and the MEG3-DMR at Human Chromosome 14q32.2 : Hierarchical Interaction and Distinct Functional Properties as Imprinting Control Centers. (2010)
  • Author(s): Kagami M, J O'Sullivan M, Green AJ, Watabe Y, Arisaka O, Masawa N, Matsuoka K, Fukami M, Matsubara K, Kato F, Ferguson-Smith AC, Ogata T.
  • Journal Title: PLoS Genetics 6(6) Pages: e1000992
  • Peer Reviewed
• [Journal Article] A Parthenogenetic Female with a Silver-Russell Syndrome-like Phenotype and a 45, X Cell Lineage Accompanied by Biparentally Derived Autosomes. (2010)
  • Author(s): Yamazawa K, Nakabayashi K, Kagami M, Satoh T, Hata K, Saitoh S, Nagai T, Horikawa R, Hizuka N, Ogata T.
  • Journal Title: Journal of Medical Genetics Epub ahead of print
  • Peer Reviewed
• [Journal Article] Maternal uniparental disomy 14 syndrome demonstrates Prader-Willi syndrome-like phenotype. (2009)
  • Author(s): Hosoki K, Kagami M, Tanaka T, Kubota M, Kurosawa K, Kato M, Uetake K, Tohyama J, Ogata T, Saitoh S.
  • Journal Title: Journal of Pediatrics 155(6) Pages: 900-903
• [Journal Article] Identification of the mouse paternally expressed imprinted gene Zdbf2 on chromosome 1 and its imprinted human homolog ZDBF2 on chromosome 2. (2009)
  • Author(s): Kobayashi H, Yamada K, Morita S, Hiura H, Fukuda A, Kagami M, Ogata T, Hata K, Sotomaru Y, Kono T.
  • Journal Title: Genomics 93(5) Pages: 461-472
  • Peer Reviewed
• [Journal Article] Placentomegaly in paternal uniparental disomy for human chromosome 14. (2008)
  • Author(s): Kagami M, Yamazawa K, Matsubara K, Matsuo N, Ogata T.
  • Journal Title: Placenta 29(8) Pages: 760-761
  • Peer Reviewed
• [Journal Article] Epimutation (hypomethylation) affecting the chromosome 14q32.2 imprinted region in a girl with upd(14)mat-like phenotype. (2008)
  • Author(s): Hosoki K, Ogata T, Kagami M, Tanaka T, Saitoh S.
  • Journal Title: European Journal of Human Genetics 16(8) Pages: 1019-1023
  • Peer Reviewed
• [Journal Article] Molecular and clinical findings and their correlations in Silver-Russell syndrome : implications for a positive role of IGF2 in growth determination and differential imprinting regulation of the IGF2-H19 domain in bodies and placentas. (2008)
  • Author(s): Yamazawa K, Kagami M, Nagai T, Kondoh T, Onigata K, Maeyama K, Hasegawa T, Hasegawa Y, Yamazaki T, Mizuno S, Miyoshi Y, Miyagawa S, Horikawa R, Matsuoka K, Ogata T.
  • Journal Title: Journal of Molecular Medicine 86(10) Pages: 1171-1181
  • Peer Reviewed
• [Journal Article] Monozygotic female twins discordant for Silver-Russell syndrome and hypomethylation of the H19-DMR. (2008)
  • Author(s): Yamazawa K, Kagami M, Fukami M, Matsubara K, Ogata T.
  • Journal Title: Journal of Human Genetics 53(10) Pages: 950-955
  • Peer Reviewed
• [Presentation] Hierarchical interaction and distinct functional properties of the IG-DMR and the MEG3-DMR at the human chromosome 14q32.2 imprinted region. (2010)
  • Author(s): Masayo Kagami, Maureen J O'Sullivan, Andrew J Green, Yoshiyuki Watabe, Osamu Arisaka, Toshiro Nagai, Shuji Takada, Maki Fukami, Kazuki Yamazawa, Keiko Matsubara, Fumiko Kato, Anne C Ferguson-Smith, Tsutomu Ogata
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: Kyoto
  • Year and Date: 20100000
• [Presentation] Hierarchical interaction and distinct functional properties of the IG-DMR and the MEG3-DMR at the human chromosome 14q32.2 imprinted region. (2010)
  • Author(s): Masayo Kagami, Maureen J O'Sullivan, Andrew J Green, Yoshiyuki Watabe , Osamu Arisaka, Toshiro Nagai, Shuji Takada, Maki Fukami, Kazuki Yamazawa, Keiko Matsubara, Fumiko Kato, Anne C Ferguson-Smith, Tsutomu Ogata
  • Organizer: International Snmposium on Pediatric Endocrinology
  • Place of Presentation: Tokyo
  • Year and Date: 20100000
• [Presentation] ヒト14q32.2のインプリンティング領域において、IG-DMRとMEG3-DMRは異なった役割をはたす (2010)
  • Author(s): 鏡雅代、高田修治、加藤芙弥子、Anne C Ferguson-Smith、緒方勤
  • Organizer: 第4回エピジェネティクス研究会
  • Place of Presentation: 鳥取
  • Year and Date: 20100000
• [Presentation] 14番染色体インプリンティング遺伝子の胎盤における機能の解明 (2010)
  • Author(s): 鏡雅代、加藤芙弥子、宮戸真美、高田修治、松岡健太郎、山中美智子、金子さおり、松原圭子、佐藤智子、緒方勤
  • Organizer: 第44回日本小児内分泌学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20100000
• [Presentation] ヒト14番染色体インプリンティング異常症発症機序の解明 (2010)
  • Author(s): 鏡雅代
  • Organizer: 第55回日本人類遺伝学会奨励賞受賞講演
  • Place of Presentation: 大宮
  • Year and Date: 20100000
• [Presentation] 14番染色体父親性ダイソミー症候群の病因別頻度の解明 (2010)
  • Author(s): 鏡雅代、加藤芙弥子、松原圭子、佐藤智子、緒方勤
  • Organizer: 第55回日本人類遺伝学会学術集会
  • Place of Presentation: 大宮
  • Year and Date: 20100000
• [Presentation] The IG-DMR and the MEG3-DMR at Human Chromosome 14q32.2 : Hierarchical Interaction and Distinct Functional Properties as Imprinting Control Centers, International Symposium on Epigenome Network (2010)
  • Author(s): Masayo Kagami, Maureen J O'Sullivan, Andrew J Green, Yoshiyuki Watabe, Osamu Arisaka, Nobuhide Masawa, Kentarou Matsuoka, Maki Fukami, Keiko Matsubara, Fumiko Kato, Anne C Ferguson-Smith, Tsutomu Ogata
  • Organizer: Development and Reprograming of Germ Cells
  • Place of Presentation: Fukuoka
  • Year and Date: 20100000
• [Presentation] RTL1 plays a key role in human placental development. International Symposium on Epigenome Network (2010)
  • Author(s): Masayo Kagami, Kentaro Matsuoka, Keiko Matsubara, Tomoko Sato, Michiko Yamanaka, Nobuhiro Suzumori, Tsutomu Ogata
  • Organizer: Development and Reprograming of Germ Cells
  • Place of Presentation: Fukuoka
  • Year and Date: 20100000
• [Presentation] Essential role of the MEG3-DMR in the regulation of the maternally inherited human chromosome 14q32.2 imprinting region. (2009)
  • Author(s): Masayo Kagami, Maki Fukami, Maureen O'Sullivan, Andrew Green, Shuji Takada, Fumiko Kato, Anne Ferguson-Smith, Tsutomu Ogata
  • Organizer: The 24th Naito Conference
  • Place of Presentation: Sapporom
  • Year and Date: 20090000
• [Presentation] 14番染色体インプリンティング遺伝子群の調節において, IG-DMRとMEG3-DMRは異なった役割をはたす (2009)
  • Author(s): 鏡雅代、高田修治、加藤芙弥子、Anne C Ferguson-Smith、緒方勤
  • Organizer: 第3回日本エピジェネティクス研究会
  • Place of Presentation: 東京
  • Year and Date: 20090000
• [Presentation] 14番染色体インプリンティング遺伝子群の調節において, IG-DMRとMEG3-DMRは異なった役割を果たす (2009)
  • Author(s): 鏡雅代、高田修治、加藤芙弥子、Anne C Ferguson-Smith、緒方勤
  • Organizer: 第54回日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 20090000
• [Presentation] 14番染色体インプリンティング遺伝子群の調節において, IG-DMRとMEG3-DMRは異なった役割をはたす (2009)
  • Author(s): 鏡雅代、高田修治、加藤芙弥子、Anne C Ferguson-Smith、緒方勤
  • Organizer: 第43回日本小児内分泌学会
  • Place of Presentation: 宇都宮
  • Year and Date: 20090000
• [Presentation] Hierarchical interaction and distinct functional properties of the IG-DMR and the MEG3-DMR at the human chromosome 14q32.2 imprinted region. (2009)
  • Author(s): Masayo Kagami, Shuji Takada, Maki Fukami, Kazuki Yamazaw, Keiko Matsubara, Fumiko Kato, Anne C Ferguson-Smith, Tsutomu Ogata
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20090000
• [Presentation] 14番染色体母性片親性ダイソミーはPrader-Willi症候群の鑑別疾患である。 (2008)
  • Author(s): 鏡雅代、斎藤伸治、高桑聖、田中藤樹、緒方勤
  • Organizer: 第42回日本小児内分泌学会学術集会
  • Place of Presentation: 米子
  • Year and Date: 20080000
• [Presentation] 14番染色体インプリンティング遺伝子群の調節にはGTL2-DMRが決定的な役割を果たす (2008)
  • Author(s): 鏡雅代、加藤芙弥子、西村玄、緒方勤
  • Organizer: 第53回日本人類遺伝学会
  • Place of Presentation: 横浜
  • Year and Date: 20080000
• [Presentation] 14番染色体父親性ダイソミー、母親性ダイソミーの表現型を招く疾患発症機序の解明 (2008)
  • Author(s): 鏡雅代、加藤芙美子、西村玄、田中葉子、黒澤健司、石野史敏、緒方勤
  • Organizer: 第111回日本小児科学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 20080000
• [Remarks] ホームページ等
  • URL: http://www.nch.go.jp/endocrinology/upd14/