The cell cycle control gene ZAC/PLAGL1 is imprinted - A strong candidate gene for transient neonatal diabetes

Mamoru Kamiya, Hannah Judson, Yasushi Okazaki, Moriaki Kusakabe, Masami Muramatsu, Shuji Takada, Nobuo Takagi, Takahiro Arima, Norio Wake, Katsunori Kamimura, Kenichi Satomura, Robert Hermann, David T. Bonthron, Yoshihide Hayashizaki

Research output: Contribution to journalArticlepeer-review

167 Citations (Scopus)

Abstract

We describe a screen for new imprinted human genes, and the identification in this way of ZAC (zinc finger protein which regulates apoptosis and cell cycle arrest)/PLAGL1 (pleomorphic adenoma of the salivary gland gene like 1) as a strong candidate gene for transient neonatal diabetes mellitus (TNDM). To screen for imprinted genes, we compared parthenogenetic DNA from the chimeric patient FD and androgenetic DNA from hydatidiform mole, using restriction landmark genome scanning for methylation. This resulted in identification of two novel imprinted loci, one of which (NV149) we mapped to the TNDM region of 6q24. From analysis of the corresponding genomic region, it was determined that NV149 lies ~ 60 kb upstream of the ZAC/PLAGL1 gene. RT-PCR analysis was used to confirm that this ZAC/PLAGL1 is expressed only from the paternal allele in a variety of tissues. TNDM is known to result from upregulation of a paternally expressed gene on chromosome 6q24. The paternal expression, map position and known biological properties of ZAC/PLAGL1 make it highly likely that it is the TNDM gene. In particular, ZAC/PLAGL1 is a transcriptional regulator of the type 1 receptor for pituitary adenylate cyclase-activating polypeptide, which is the most potent known insulin secretagog and an important mediator of autocrine control of insulin secretion in the pancreatic islet.

Original languageEnglish
Pages (from-to)453-460
Number of pages8
JournalHuman molecular genetics
Volume9
Issue number3
DOIs
Publication statusPublished - 2000 Feb 12
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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