Elucidation of the transcriptional regulation based on identification of the ABO gene enhancer

• Project/Area Number: 25460861
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Gunma University
• Principal Investigator: Nakajima Tamiko 群馬大学, 医学(系)研究科(研究院), 研究員 (40008561)
• Co-Investigator(Kenkyū-buntansha): KOMINATO Yoshihiko 群馬大学, 大学院医学系研究科, 教授 (30205512) ; SANO Rie 群馬大学, 大学院医学系研究科, 講師 (70455955)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: ABO遺伝子 / 転写因子 / 転写調節 / エンハンサー / 血液型亜型 / 遺伝子発現 / ハプロタイプ / 変異型 / エンハンサ－

Outline of Final Research Achievements

Recently, we have identified an erythroid cell-specific regulatory element (+5.8-kb site) in the first intron of the human ABO blood group gene. In this study, we have concluded that Bm is caused by a reduction of B gene expression in bone marrow cells by in vitro erythroid culture of Bm-derived CD34+ cells. A 5.8-kb or 3.0-kb deletion including the +5.8-kb site was observed Bm and ABm individuals. Moreover, RUNX1, GATA-1 and GATA-2 are bound to the site through their recognition motifs, deletion or mutation of which were involved in subgroups Am, Bm and A3. Genetic studies of common ABO phenotype of Japanese have demonstrated six haplotypes of the +5.8-kb site consists of six SNPs. Each haplotype was mostly linked with specific ABO alleles with a few exceptions, possibly as a result of hybrid formation between common ABO alleles.

Research Products

• [Journal Article] Presence of nucleotide substitutions in the ABO promoter in individuals with phenotypes A3 and B3. (2016)
  • Author(s): Isa K, Yamamuro Y, Ogasawara K, Yabe R, Ogiyama Y, Ito S, Takahashi Y, Y Kominato Y, Sano R, Uchikawa M.
  • Journal Title: Vox Sang. Volume: 110 Issue: 3 Pages: 285-287
  • DOI: 10.1111/vox.12363
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] BO alleles are linked with haplotypes of an erythroid cell-specific regulatory element in intron 1 with a few exceptions attributable to genetic recombination. (2016)
  • Author(s): Nakajima T, Sano R, Takahashi Y, Watanabe K, Kubo R, Kobayashi M, Takahashi K, Takeshita H, Kominato Y.
  • Journal Title: Vox Sang. Volume: 11 Issue: 1 Pages: 90-92
  • DOI: 10.1111/vox.12312
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of a single nucleotide polymorphism (rs6180 ) in GHR gene with plural tissue weight (2016)
  • Author(s): Fujihara J, Kimura-Kataoka K, Yasuda T, Sano R, Kominato Y, Takeshita H.
  • Journal Title: J Genet. Volume: 95 Pages: 189-192
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Intestinal obstruction in a mentally retarded patient due to pica. (2015)
  • Author(s): Tokue H, Takahashi Y, Hirasawa S, Awata S, Kobayashi S, Shimada T, Tokue A, Sano R, Kominato Y, Tsushima Y
  • Journal Title: Ann Gen Psychiatry Volume: 31 Issue: 1 Pages: 22-22
  • DOI: 10.1186/s12991-015-0060-4
  • Peer Reviewed / Open Access
• [Journal Article] Global analysis of genetic variations in a 56-bp variable number of tandem repeat polymorphisms within the human deoxyribonuclease I gene (2015)
  • Author(s): Junko Fujihara
  • Journal Title: Legal Medicine Volume: 印刷中 Issue: 4 Pages: 283-286
  • DOI: 10.1016/j.legalmed.2015.01.005
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of five cases of suspected bathtub suicide. (2015)
  • Author(s): Murayama M, Takahashi Y, Sano R, Watanabe K, Takahashi K, Kubo R, Kuninaka H, Kominato Y
  • Journal Title: Leg Medicine. Volume: 13 Issue: 6 Pages: 576-578
  • DOI: 10.1016/j.legalmed.2015.07.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Brain fragility can be estimated by its putative signs on postmortem computed tomography. (2015)
  • Author(s): Watanabe K, Takahashi Y, Sano R, Nakajima T, Kominato Y, Kobayashi S, Shimada T, Takei H, Awata S, Hirasawa S
  • Journal Title: Legal Medicine Volume: 17 Issue: 2 Pages: 98-101
  • DOI: 10.1016/j.legalmed.2014.10.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A 3.0-kb delation including an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene in an individual with the Bm phenotype (2015)
  • Author(s): Sano R, Kuboya E, Nakajima T, Takahashi Y, Takahashi K, Kubo R, Kominato Y, Takeshita H, Yamao H, Kishida T, Isa K, Ogasawara K, Uchikawa M
  • Journal Title: Vox Sang Volume: 108 Issue: 3 Pages: 310-313
  • DOI: 10.1111/vox.12216
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Blood group gene is barely expressed in vitro erythroid culture of Bm-derived CD34+ cells without an erythroid cell-specific regulatory element (2015)
  • Author(s): Sano R, Nogawa T, Nakajima T, Takahashi Y, Kubo R, Kominato Y, Yokohama A, Tsukada J, Yamao H, Kishida T, Ogasawara K, Uchikawa M
  • Journal Title: Vox Sang Volume: 108 Issue: 3 Pages: 302-309
  • DOI: 10.1111/vox.12220
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ABO 遺伝子の転写調節領域の変異により血液型亜型Am型、A3型、B3型が生じる. (2015)
  • Author(s): 高橋遥一郎, 佐野利恵, 中島たみ子, 小湊慶彦.
  • Journal Title: DNA多型 Volume: 23 Pages: 103-107
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ABO chimerism with a minor allele detected by the PNA-mediated PCR clamping method (2014)
  • Author(s): Sano R, Takahashi Y, Nakajima T, Yoshii M, Kubo R, Takahashi K, Kominato Y, Takeshita H, Yasuda T, Tsuneyama H, Uchikawa M, Isa K, Ogasawara K:
  • Journal Title: Blood Transfusion Volume: 12 Pages: 431-434
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Presence of nucleotide substitutions in transcriptional regulatory elements such as the erythroid cell-specific enhancer-like element and the ABO promoter in individuals with phenotypes A3 and B3, respectively (2014)
  • Author(s): Takahashi Y, Isa K, Sano R, Nakajima T, Kubo R, Takahashi K, Kominato Y, Michino J, Masuno A, Tsuneyama H, Ito S, Ogasawara K, Uchikawa M
  • Journal Title: Vox Sang Volume: 107 Issue: 2 Pages: 171-180
  • DOI: 10.1111/vox.12136
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ABO式遺伝子血球系特異的エンハンサー内GATAサイトの一塩基置換がB抗原量の低下をもたらしたBm型一症例 (2014)
  • Author(s): 佐野利恵, 中島たみ子, 高橋遥一郎, 高橋圭子，久保谷江里，小湊慶彦，藤原純子, 竹下治男，安田年博，岸田哲子
  • Journal Title: DNA多型 Volume: 22 Pages: 109-113
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Deletion of the RUNX1 binding site in the erythroid cell-specific regulatory element of the ABO gene in two individuals with the Am phenotype. (2014)
  • Author(s): Takahashi Y, Isa K, Sano R, Nakajima T, Kubo R, Takahashi K, Kominato Y, Tsuneyama H, Ogasawara K, Uchikawa M
  • Journal Title: Vox Sang Volume: 106 Issue: 2 Pages: 167-175
  • DOI: 10.1111/vox.12077
  • Peer Reviewed / Open Access
• [Journal Article] Mutation of the GATA site in the erythroid cell-specific regulatory element of the ABO gene in a Bm subgroup individual (2013)
  • Author(s): Tamiko Nakajima
  • Journal Title: Transfusion Volume: 53 Issue: 11pt2 Pages: 2917-2927
  • DOI: 10.1111/trf.12181
  • Peer Reviewed
• [Journal Article] ABO式血液型遺伝子エンハンサー欠損がBm型の原因である. (2013)
  • Author(s): 佐野利恵, 中島たみ子, 高橋遥一郎, 小湊慶彦.
  • Journal Title: DNA多型 Volume: 21 Pages: 122-126
  • Peer Reviewed
• [Presentation] Bm型では赤血球系細胞においてB遺伝子の発現が極めて低下している－CD34陽性細胞を用いた赤血球系細胞への分化培養実験－ (2015)
  • Author(s): 佐野利恵、中島たみ子、高橋遥一郎、小湊慶彦
  • Organizer: 日本DNA多型学会第24回学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2015-11-20
• [Presentation] ABO式血液型遺伝子エンハンサーハプロタイプの型特異性 (2015)
  • Author(s): 中島 たみ子、佐野利恵、高橋遥一郎、窪 理英子、高橋圭子、小林もも子、渡邊華帆、小湊慶彦、竹下治男、安田年博
  • Organizer: 日本DNA多型学会第24回学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2015-11-20
• [Presentation] Growth hormone receptor(GHR)遺伝子におけるSNP(rs6180)と臓器重量との関連 (2015)
  • Author(s): 藤原純子、竹下治男、木村かおり、植木美鈴、安田年博、佐野利恵、小湊慶彦、倉田さつき
  • Organizer: 日本DNA多型学会第24回学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2015-11-20
• [Presentation] 浴槽内での自殺が疑われた５症例の検討. (2015)
  • Author(s): 村山真之、高橋遥一郎、佐野利恵、小湊慶彦
  • Organizer: 第84回日本法医学会学術関東地方集会
  • Place of Presentation: 東京
  • Year and Date: 2015-10-24
• [Presentation] 死後CT検査により同定された左室心筋石灰化、心肥大が診断の一助となった左冠動脈肺動脈起始症の一症例 (2015)
  • Author(s): 佐野利恵、高橋遥一郎、中島たみ子、小湊慶彦
  • Organizer: 第99次日本法医学会学術全国集会
  • Place of Presentation: 高知
  • Year and Date: 2015-06-12
• [Presentation] 特異な状況下で生じた空気塞栓症の診断に死後画像検査が有用であった一例 (2015)
  • Author(s): 高橋遥一郎、佐野利恵、中島たみ子、小湊慶彦
  • Organizer: 第99次日本法医学会学術全国集会.
  • Place of Presentation: 高知
  • Year and Date: 2015-06-12
• [Presentation] 酸化亜鉛ナノ粒子の静脈投与後の毒性精査 (2015)
  • Author(s): 藤原純子、木村かおり、竹下治男、飯田礼子、安田年博、佐野利恵、小湊慶彦
  • Organizer: 第99次日本法医学会学術全国集会
  • Place of Presentation: 高知
  • Year and Date: 2015-06-12
• [Presentation] Bm型では赤血球系細胞においてB遺伝子発現が極めて低下している-CD34陽性細胞を用いた分化培養実験- (2015)
  • Author(s): 佐野利恵、中島たみ子、高橋遥一郎、竹下治男、安田年博、岸田哲子、小湊慶彦
  • Organizer: 第99次日本法医学会学術全国集会
  • Place of Presentation: 高知
  • Year and Date: 2015-06-11
• [Presentation] Pathological and genetic mechanism of FAO disorders in two infants of sudden unexpected death (2015)
  • Author(s): 高橋遥一郎、佐野利恵、中島たみ子、小湊慶彦
  • Organizer: 第99次日本法医学会学術全国集会
  • Place of Presentation: 高知
  • Year and Date: 2015-06-11
• [Presentation] ABO遺伝子の転写調節領域の変異により血液型亜型Am型，A3型，B3型が生じる (2014)
  • Author(s): 高橋遥一郎，佐野利恵，中島たみ子，小湊慶彦
  • Organizer: 日本DNA多型学会第23回学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-11-27
• [Presentation] Mutations were found in the transcription-regulatory elements such as the promoter and the erythroid cell-specific enhancer of ABO in individuals with phenotypes Am, A3 and B3 (2014)
  • Author(s): Takahashi Y, Sano R, Nakajima T, Takeshita H, Yasuda T, Kominato Y
  • Organizer: 9th International Symposium on Advances in Legal Medicine (ISALM)
  • Place of Presentation: 福岡
  • Year and Date: 2014-06-17
• [Presentation] ABO chimerism with a minor allele detected by the PNA－mediated PCR clamping method (2014)
  • Author(s): Sano R, Takahashi Y, Nakajima T, Yoshii M, Kubo R, Takahashi K, Kominato Y, Takeshita H, Yasuda T
  • Organizer: 9th International Symposium on Advances in Legal Medicine (ISALM)
  • Place of Presentation: 福岡
  • Year and Date: 2014-06-17
• [Presentation] Blood group B gene is sharply reduced in the erythroid-lineage progenitor cells of a Bm individual with deletion of an erythroid cell-specific enhancer (2014)
  • Author(s): Sano R, Nogawa M, Nakajima T, Takahashi Y, Kominato Y, Yokohama A, Yamao H, Kishida T, Isa K, Ogasawara K, Uchikawa M
  • Organizer: 33rd International Congress of the International Society of Blood Transfusion
  • Place of Presentation: Seoul
  • Year and Date: 2014-06-03
• [Presentation] MUTATION OF THE TRANSCRIPTION REGULATION REGIONS IN THE ABO GENE ACCOUNTING FOR A3 AND B3 PHENOTYPES (2014)
  • Author(s): Isa K, Ogasawara K , Ito S, Tsuneyama H, Yabe R, Takahashi Y, Sano R,Nakajima T, Kominato Y, Uchikawa M, Satake M and Tadokoro K
  • Organizer: 33rd International Congress of the International Society of Blood Transfusion
  • Place of Presentation: Seoul
  • Year and Date: 2014-06-03
• [Presentation] 赤血球系細胞特異的な転写制御領域に一塩基置換を認めたA3型 (2014)
  • Author(s): 伊藤正一，荻山佳子，高橋美都保，小原健良，伊藤 孝，常山初江，伊佐和美，小笠原健一，内川 誠，高橋遥一郎，佐野利恵，中島たみ子，小湊慶彦
  • Organizer: 第62回日本輸血・細胞治療学会総会
  • Place of Presentation: 奈良
  • Year and Date: 2014-05-15
• [Presentation] ABOプロモーター領域に変異を認めたB3型 －ABO遺伝子全長PCR法による解析－ (2014)
  • Author(s): 伊佐和美，小笠原健一，佐竹正博，田所憲治，伊藤正一，常山初江，矢部隆一,内川 誠，高橋遥一郎，佐野利恵，中島たみ子，小湊慶彦
  • Organizer: 第62回日本輸血・細胞治療学会総会
  • Place of Presentation: 奈良
  • Year and Date: 2014-05-15
• [Presentation] A遺伝子イントロン1の転写制御領域に23bpの欠失がみられた日本人Am型の2例 (2014)
  • Author(s): 増田英敏，常山初江，伊佐和美，小笠原健一，矢部隆一，内川 誠，南 孝彦，高橋遥一郎，佐野利恵，中島たみ子，小湊慶彦
  • Organizer: 第62回日本輸血・細胞治療学会総会
  • Place of Presentation: 奈良
  • Year and Date: 2014-05-15
• [Presentation] ABO遺伝子血球系特異的エンハンサー内GATAサイトの一塩基置換がB抗原量の低下をもたらしたBm型一症例. (2013)
  • Author(s): 佐野利恵, 中島たみ子, 高橋遥一郎, 高橋圭子, 藤原純子, 竹下治男, 安田年博, 小湊慶彦, 岸田哲子.
  • Organizer: DNA多型学会第22回学術集会
  • Place of Presentation: 仙台
• [Presentation] ABO式血液型の転写調節機構の解明と血液型亜型の解析. (2013)
  • Author(s): 佐野利恵
  • Organizer: 第60回北関東医学会総会
  • Place of Presentation: 前橋
• [Presentation] ABO遺伝子血球系特異的エンハンサー内GATAサイトの一塩基置換がB抗原量の低下をもたらしたBm型一症例. (2013)
  • Author(s): 佐野利恵, 中島たみ子, 高橋遥一郎, 高橋圭子, 竹下治男, 安田年博, 小湊慶彦.
  • Organizer: 第97次日本法医学会学術全国集会
  • Place of Presentation: 札幌
• [Presentation] 日本人のBm型に関する遺伝子の解析. (2013)
  • Author(s): 伊佐和美, 小笠原健一, 佐々木佳奈, 岡崎仁, 田所憲治, 國井七絵, 小野寺孝行, 斎藤昌子, 常山初江, 矢部隆一, 内川誠, 佐野利恵, 中島たみ子, 小湊慶彦, 丸橋隆行, 横濱章彦.
  • Organizer: 第61回日本輸血・細胞治療学会総会
  • Place of Presentation: 横浜
• [Presentation] MOLECULAR BASIS FOR JAPANESE INDIVIDUALS WITH Bm AND Am. (2013)
  • Author(s): Ogasawara K, ISA K, Tsuneyama H, Saito M, Okazaki H, Satake M, Tadokoro K, Sano R, Nakajima T, Kominato Y, Maruhashi T, Yokohama A and Uchikawa M.
  • Organizer: the 23rd Regional Congress of the ISBT
  • Place of Presentation: Amsterdam