TY - JOUR
T1 - Human glycine decarboxylase gene (GLDC) and its highly conserved processed pseudogene (ψGLDC)
T2 - Their structure and expression, and the identification of a large deletion in a family with nonketotic hyperglycinemia
AU - Takayanagi, Masaru
AU - Kure, Shigeo
AU - Sakata, Yoshiyuki
AU - Kurihara, Yukiko
AU - Ohya, Yukihiro
AU - Kajita, Mitsuharu
AU - Tada, Keiya
AU - Matsubara, Yoichi
AU - Narisawa, Kuniaki
N1 - Funding Information:
Acknowledgments This work was supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, and the Ministry of Health and Welfare of Japan.
PY - 2000
Y1 - 2000
N2 - Mutations in the glycine decarboxylase gene (GLDC) cause nonketotic hyperglycinemia (NKH), an inborn error of metabolism characterized by severe neurological disturbance. We have determined the structure of GLDC and of its pseudogene (ψGLDC) and studied their expression for a molecular analysis of NKH. The GLDC gene spans at least 135 kb and consists of 25 exons. All donor and acceptor sites adhere to the canonical GT-AG rule, except for the donor site of intron 21, where a variant form GC is used instead of GT. The transcription initiation site has been assigned to a residue 163 bp upstream from the translation initiation triplet by primer extension analysis. The ψGLDC gene has no intron and shares 97.5% homology with the coding region of functional GLDC, suggesting that ψGLDC is a processed pseudogene that arose from the GLDC transcript about 4-8 million years ago. RNA blotting analysis has revealed that GLDC is expressed in human liver, kidney, brain, and placenta. We have also examined a patient with NKH with no detectable GLDC mRNA in his lymphoblasts. Exons 1-3 of the functional GLDC gene from this patient are not amplified by polymerase chain reaction (PCR), whereas those from control subjects are. These results suggest a large homozygous deletion (at least 30 kb) in the patient. Furthermore, we have devised a semi-quantitative PCR to estimate the number of GLDC alleles by using ψGLDC as an internal control and have confirmed the homozygosity and heterozygosity of the deletion in the patient and his parents, respectively. Structural information of GLDC and ψGLDC should facilitate the molecular analysis of NKH.
AB - Mutations in the glycine decarboxylase gene (GLDC) cause nonketotic hyperglycinemia (NKH), an inborn error of metabolism characterized by severe neurological disturbance. We have determined the structure of GLDC and of its pseudogene (ψGLDC) and studied their expression for a molecular analysis of NKH. The GLDC gene spans at least 135 kb and consists of 25 exons. All donor and acceptor sites adhere to the canonical GT-AG rule, except for the donor site of intron 21, where a variant form GC is used instead of GT. The transcription initiation site has been assigned to a residue 163 bp upstream from the translation initiation triplet by primer extension analysis. The ψGLDC gene has no intron and shares 97.5% homology with the coding region of functional GLDC, suggesting that ψGLDC is a processed pseudogene that arose from the GLDC transcript about 4-8 million years ago. RNA blotting analysis has revealed that GLDC is expressed in human liver, kidney, brain, and placenta. We have also examined a patient with NKH with no detectable GLDC mRNA in his lymphoblasts. Exons 1-3 of the functional GLDC gene from this patient are not amplified by polymerase chain reaction (PCR), whereas those from control subjects are. These results suggest a large homozygous deletion (at least 30 kb) in the patient. Furthermore, we have devised a semi-quantitative PCR to estimate the number of GLDC alleles by using ψGLDC as an internal control and have confirmed the homozygosity and heterozygosity of the deletion in the patient and his parents, respectively. Structural information of GLDC and ψGLDC should facilitate the molecular analysis of NKH.
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U2 - 10.1007/s004390051041
DO - 10.1007/s004390051041
M3 - Article
C2 - 10798358
AN - SCOPUS:0034036029
VL - 106
SP - 298
EP - 305
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 3
ER -