1999 Fiscal Year Final Research Report Summary
Recurrent deletion in glycine decarboxylase gene and nonketotic hyperglycinemia Medical genetics, Research
| Project/Area Number |
10672134
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
KURE Shigeo Pediatrics, Tohoku University Associate professor, 大学院・医学系研究科, 助手 (10205221)
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| Co-Investigator(Kenkyū-buntansha) |
OHURA Toshihiro Pediatrics, Tohoku University Associate professor, 大学院・医学系研究科, 助教授 (10176828)
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| Project Period (FY) |
1998 – 1999
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| Keywords | glycine decarboxylase / Alu repeats / non-ketotic hyperglycinemia / deletion / homologous recombination |
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| Research Abstract |
Mutations in glycine decarboxylase gene (GLDC) cause nonketotic hyperglycinemia (NKH), an inborn error of metabolism characterized by severe neurological disturbance. We determined the structures of GLDC and its pseudogene (psiGLDC) and studied their expression in molecular analysis of NKH. The GLDC gene spanned a least 135 kb and consisted of 25 exons. All donor and acceptor sites adhered to the canonical GT-AG rule except for the donor site of intron 21, where a variant form GC was used instead of GT. The transcription initiation site was assigned to a residue 163 bp upstream from the translation initiation triplet by primer extension analysis. The psiGLDC gene had no intron and shared 97.5% homology with the coding region of functional GLDC, suggesting that psiGLDC ia a processed pseudogene that arose from the GLDC transcript about 4 to 8 million years ago. RNA blotting analysis revealed that GLDC is expressed in human liver, kidney, brain and placenta. We then examined a patient with NKH with no detectable GLDC mRNA in his lymphoblasts. Exons 1 to 3 of the functional GLDC gene from this patient were not amplified by PCR, whereas those from control subjects were amplified. These results suggest a large homozygous deletion (at least 30 kb) in the patient. We then devise a semi-quantitative PCR to estimate the number of GLDC alleles using psiGLDC as an internal control, and confirmed the homozygosity and heterozygosity of the deletion in the patient and his parents, respectively. Structural information of GLDC and psiGLDC should facilitate the molecular analysis of NKH.
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[Publications] Nagasaki Y, Matsubara Y, Takano H, Fujii K, Senoo M, Akanuma J, Takahasi K, Kure S, Hara M, Kanagane Y, Saito I, Narisawa K.: "Reversal of hypopigmentation in phenylketonuria mice by adenovirus-mediated gene transfer."Pediatric Res. 45. 465-73 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Fujii K, Matsubara Y, Akanuma J, Takahashi K, Kure S, Suzuki Y, Imaizumi M, Iinuma K, Sakatsme O, Rinaldo P, Kuniaki Narisawa.: "Mutation detection by TaqMan-allele specific amplification: its application to the molecular diagnosis of glycogen storage disease type Ia and medium-chain acyl-CoA dehydrogenase deficiency."Hum Mutaion. 15. 189-196 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Takayanagi M, Kure S, Tada K, Sakata Y, Kurihara Y, Ohya Y, Kajita M, Tada K, Matsubara Y, Narisawa K.: "Human glycine decarboxylase (GLCD) gene and its processed type pseudogene: Structures, expression, and identification of a large deletion in a family with nonketotic hyperglycinemia."Human Genet. (in press).
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「研究成果報告書概要(欧文)」より
