Biallelic expression of HRAS and MUCDHL in human and mouse

Hum Genet. 2003 Apr;112(4):334-42. doi: 10.1007/s00439-003-0907-7. Epub 2003 Feb 14.

Abstract

At least eight genes clustered in 1 Mb of DNA on human chromosome (Chr) 11p15.5 are subject to parental imprinting, with monoallelic expression in one or more tissues. Orthologues of these genes show conserved linkage and imprinting on distal Chr 7 of mice. The extended imprinted region has a bipartite structure, with at least two differentially methylated DNA elements (DMRs) controlling the imprinting of two sub-domains. We previously described three biallelically expressed genes ( MRPL23, 2G7 and TNNT3) in 100 kb of DNA immediately downstream of the imprinted H19 gene, suggesting that H19 marks one border of the imprinted region. Here we extend this analysis to two additional downstream genes, HRAS and MUCDHL (mu-protocadherin). We find that these genes are biallelically expressed in multiple fetal and adult tissues, both in humans and in mice. The mouse orthologue of a third gene, DUSP8, located between H19 and MUCDHL, is also expressed biallelically. The DMR immediately upstream of H19 frequently shows a net gain of methylation in Wilms tumors, either via Chr 11p15.5 loss of heterozygosity (LOH) or loss of imprinting (LOI), but changes in methylation in CpG-rich sequences upstream and within the MUCDHL gene are rare in these tumors and do not correlate with LOH or LOI. These findings are further evidence for a border of the imprinted region immediately downstream of H19, and the data allow the construction of an imprinting map that includes more than 20 genes, distributed over 3 Mb of DNA on Chr 11p15.5.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles*
  • Animals
  • Blotting, Southern
  • Cadherin Related Proteins
  • Cadherins / genetics*
  • Chromosomes, Human, Pair 11 / genetics*
  • DNA Methylation
  • Gene Expression Regulation
  • Genes, ras / genetics*
  • Genetic Linkage
  • Genomic Imprinting
  • Humans
  • Mice
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single-Stranded Conformational
  • Protocadherins
  • RNA, Long Noncoding
  • RNA, Messenger / analysis
  • RNA, Untranslated / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Sulfites / metabolism

Substances

  • CDHR5 protein, human
  • Cadherin Related Proteins
  • Cadherins
  • H19 long non-coding RNA
  • Mucdhl protein, mouse
  • Protocadherins
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Untranslated
  • Sulfites
  • hydrogen sulfite