Chromosomal localization, structure, single-nucleotide polymorphisms, and expression of the human H-protein gene of the glycine cleavage system (GCSH), a candidate gene for nonketotic hyperglycinemia

S. Kure, K. Kojima, T. Kudo, K. Kanno, Y. Aoki, Y. Suzuki, T. Shinka, Y. Sakata, K. Narisawa, Y. Matsubara

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Nonketotic hyperglycinemia (NKH) is an inborn error of metabolism caused by deficiency in the glycine cleavage system (GCS); this system consists of four individual constituents, P-, T-, H-, and L-proteins. Several mutations have been identified in P- and T-protein genes, but not in the H-protein gene (GCSH), despite the presence of case reports of H-protein deficiency. To facilitate the mutational and functional analyses of GCSH, we isolated and characterized a human p1-derived artificial chromosome (PAC) clone encoding GCSH. GCSH spanned 13.5 kb and consisted of five exons. Using the PAC clone as a probe, we mapped GCSH to chromosome 16q24 by fluorescence in situ hybridization. The transcription initiation site was determined by the oligonucleotide-cap method, and potential binding sites for several transcriptional factors were found in the 5′ upstream region. Direct sequencing analysis revealed five single-nucleotide polymorphisms. The expression profiles of P-, T-, and H-protein mRNAs were studied by dot-blot analysis, using total RNA from various human tissues. GCSH was expressed in all 29 tissues examined, while T-protein mRNA was detected in 27 of the 29 tissues. In contrast, the P-protein gene was expressed in a limited number of tissues, such as liver, kidney, brain, pituitary gland, and thyroid gland, suggesting distinct transcriptional regulation of each GCS constituent.

Original languageEnglish
Pages (from-to)378-384
Number of pages7
JournalJournal of Human Genetics
Volume46
Issue number7
DOIs
Publication statusPublished - 2001

Keywords

  • Direct sequencing analysis
  • Fluorescence in situ hybridization
  • Human PAC clone
  • RNA blot analysis
  • Transcription initiation site

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Chromosomal localization, structure, single-nucleotide polymorphisms, and expression of the human H-protein gene of the glycine cleavage system (GCSH), a candidate gene for nonketotic hyperglycinemia'. Together they form a unique fingerprint.

Cite this