Development of noninvasive prenatal diagnosis by using maternal blood

• Project/Area Number: 15591163
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Showa University School of Medicine
• Principal Investigator: SEKIZAWA Akihiko Showa Univ, School of Med, MD, Associate Professor, 医学部, 講師 (10245839)
• Co-Investigator(Kenkyū-buntansha): ICHIZUKA Kiyotake Showa Univ, School of Med, MD, Assistant Professor, 医学部, 助手 (00338451) ; MATSUOKA Ryu Showa Univ, School of Med, MD, Assistant Professor, 医学部, 助手 (20349111)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: cell-free DNA / placental damage / preeclampsia / fetal diagnosis / nonivasive approach / gene test / 遺伝子検査 / 妊娠中毒症 / DNA / 母体血 / 浮遊DNA / DYS14遣伝子 / real time PCR

Research Abstract

Circulating fetal DNA in maternal plasma can be used for both fetal genetic testing and evaluation of complications of pregnancy. As a prenatal genetic test, the greatest feature of this approach is the lack of risk. This approach was applied to the diagnosis of fetal gender, fetal RhD blood type, and fetal single-gene-disorders. However, this plasma DNA approach only allows examination of disorders where the gene of interest is present in the fetal genome but absent from maternal DNA. Since the majority of fetal DNA probably originates from villous trophoblasts, concentrations can be used for the evaluation of damage to trophoblasts, particularly in the pathological complications of pregnancy, such as pre-eclampsia, invasive placenta, hyperemesis gravidarum, and trisomy 21. Fetal DNA in the plasma of pregnant women thus offers a new source of data that can be used in various clinical settings.

Research Products

• [Journal Article] Fragmentation of cell-free fetal DNA in plasma and urine of pregnant women. (2005)
  • Author(s): Koide K, Sekizawa A, Iwasaki M, Matsuoka R, Honma S, Farina A, Saito H, Okai T
  • Journal Title: Prenatal Diagnosis 25(7) Pages: 604-7
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Lower Maternal PLAC1 mRNA in Pregnancies Complicated with Vaginal Bleeding (Threatened Abortion <20 Weeks) and a Surviving Fetus (2005)
  • Author(s): Farina A, Rizzo N, Concu M, Banzola I, Sekizawa A, Grotti S, Carinci P
  • Journal Title: Clinical Chemistry 51(1) Pages: 224-7
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Fragmentation of cell-free fetal DNA in plasma and urine of pregnant women. (2005)
  • Author(s): Koide K, Sekizawa A, Iwasaki M, Matsuoka R, Honma S, Farina A, Saito H, Okai T
  • Journal Title: Prenatal Diagnosis. Jul;25(7) Pages: 604-607
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Lower Maternal PLAC1 mRNA in Pregnancies Complicated with Vaginal Bleeding (Threatened Abortion <20 Weeks) and a Surviving Fetus (2005)
  • Author(s): Farina A, Rizzo N, Concu M, Banzola I, Sekizawa A, Grotti S, Carinci P
  • Journal Title: Clinical Chemistry. Jan;51(1) Pages: 224-227
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Fragmentation of cell-free fatal DNA in plasma and urine of pregnant women. (2005)
  • Author(s): Koide K, Sekizawa A, Iwasaki M, Matsuoka R, Honma S, Farina A, Saito H, Okai T
  • Journal Title: Prenatal Diagnosis 25・7 Pages: 604-607
• [Journal Article] Proteinuria and hypertension are independent factors affecting fetal DNA values : a retrospective analysis of affected and unaffected patients. (2004)
  • Author(s): Sekizawa A, Farina A, Sugito Y, Matsuoka R, Iwasaki M, Saito H, Okai T.
  • Journal Title: Clinical Chemistry 50(1)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Beta-globin DNA in maternal plasma as a molecular marker of pre-eclampsia. (2004)
  • Author(s): Sekizawa, A., Farina, A., Koide, K., Iwasaki, M., Honma, S., Ichizuka, K., Saito, H., Okai,T
  • Journal Title: Prenatal Diagnosis 24 Pages: 697-700
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Total cell-free DNA (beta-globin gene) distribution in maternal plasma at the second trimester : a new prospective for reeclampsia screening (2004)
  • Author(s): Farina, A., Sekizawa, A., Iwasaki, M., Matsuoka, R., Ichizuka, K., Okai,T.
  • Journal Title: Prenatal Diagnosis 24 Pages: 722-726
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Proteinuria and hypertension are independent factors affecting fetal DNA values : a retrospective analysis of affected and unaffected patients. (2004)
  • Author(s): Sekizawa A, Farina A, Sugito Y, Matsuoka R, Iwasaki M, Saito H, Okai T.
  • Journal Title: Clinical Chemistry. Jan;50(1) Pages: 221-224
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Beta-globin DNA in maternal plasma as a molecular marker of pre-eclampsia. (2004)
  • Author(s): Sekizawa, A.Farina, A., Koide, K., Iwasaki, M., Honma, S., Ichizuka, K., Saito, H., Okai, T.
  • Journal Title: Prenatal Diagnosis 24 Pages: 697-700
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Total cell-free DNA (beta-globin gene) distribution in maternal plasma at the second trimester : a new prospective for preeclampsia screening (2004)
  • Author(s): Farina, A., Sekizawa, A., Iwasaki, M., Matsuoka, R., Ichizuka, K., Okai, T.
  • Journal Title: Prenatal Diagnosis 24 Pages: 722-726
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] β-globin DNA in maternal plasma as a molecular marker of pre-eclampsia (2004)
  • Author(s): Sekizawa A, et al.
  • Journal Title: Prenatal Diagnosis 24 Pages: 697-700
• [Journal Article] Total cell-free DNA distribution in maternal plasma at the second trimeter : a new prospective for PE (2004)
  • Author(s): Farina A, Sekizawa A, et al.
  • Journal Title: Prenatal Diagnosis 24 Pages: 722-726
• [Journal Article] Evaluation of bidirectional transfer of plasma DNA through placenta (2003)
  • Author(s): Sekizawa A, Yokokawa K, Sugito Y, Iwasaki M, Yukimoto Y, Ichizuka K, Saito H, Okai T
  • Journal Title: Human Genetics 113(4) Pages: 307-10
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Evaluation of bidirectional transfer of plasma DNA through placenta (2003)
  • Author(s): Sekizawa A, Yokokawa K, Sugito Y, Iwasaki M, Yukimoto Y, Ichizuka K, Saito H, Okai T
  • Journal Title: Human Genetics. Sep;113(4) Pages: 307-310
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Farina A, Sekizawa A, et al.: "Fetal DNA maternal plasma as a screening variable for preeclampsia. A preliminary nonparametric analysis of detection rate in low-risk nonsymptomatic patients"Prenatal Diagnosis. 24(in press). (2004)
• [Publications] Sekizawa A, Yukimoto Y et al.: "Evaluation of bidirectional transfer of plasma DNA through placenta"Hum Genet. 113(4). 307-310 (2003)
• [Publications] Sugito Y, Yukimoto Y et al.: "Relationship between Severity of Hyperemesis Gravidarum and Fetal DNA Concentration in Maternal Plasma"Clin Chem. 49(10). 1667-1669 (2003)
• [Publications] Sekizawa A et al.: "Proteinuria and hypertension are two independent factors affecting fetal DNA values : a retrospective analysis of affected and unaffected patients"Clin Chem. 50(1)(in press). (2004)