Epigenetic detection of human chromosome 14 uniparental disomy.

Journal Article (Journal Article)

The recent demonstration of genomic imprinting of DLK1 and MEG3 on human chromosome 14q32 indicates that these genes might contribute to the discordant phenotypes associated with uniparental disomy (UPD) of chromosome 14. Regulation of imprinted expression of DLK1 and MEG3 involves a differentially methylated region (DMR) that encompasses the MEG3 promoter. We exploited the normal differential methylation of the DLK1/MEG3 region to develop a rapid diagnostic PCR assay based upon an individual's epigenetic profile. We used methylation-specific multiplex PCR in a retrospective analysis to amplify divergent lengths of the methylated and unmethylated MEG3 DMR in a single reaction and accurately identified normal, maternal UPD14, and paternal UPD14 in bisulfite converted DNA samples. This approach, which is based solely on differential epigenetic profiles, may be generally applicable for rapidly and economically screening for other imprinting defects associated with uniparental disomy, determining loss of heterozygosity of imprinted tumor suppressor genes, and identifying gene-specific hypermethylation events associated with neoplastic progression.

Full Text

Duke Authors

Cited Authors

  • Murphy, SK; Wylie, AA; Coveler, KJ; Cotter, PD; Papenhausen, PR; Sutton, VR; Shaffer, LG; Jirtle, RL

Published Date

  • July 2003

Published In

Volume / Issue

  • 22 / 1

Start / End Page

  • 92 - 97

PubMed ID

  • 12815599

Electronic International Standard Serial Number (EISSN)

  • 1098-1004

Digital Object Identifier (DOI)

  • 10.1002/humu.10237


  • eng

Conference Location

  • United States