Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation

  1. Lili Milani1,
  2. Anders Lundmark1,
  3. Jessica Nordlund1,
  4. Anna Kiialainen1,
  5. Trond Flaegstad2,
  6. Gudmundur Jonmundsson3,
  7. Jukka Kanerva4,
  8. Kjeld Schmiegelow5,
  9. Kevin L Gunderson6,
  10. Gudmar Lonnerholm7, and
  11. Ann-Christine Syvanen1,8
  1. 1 Uppsala University;
  2. 2 Tromsoe University and University Hospital;
  3. 3 Landspitalinn Reykjavik;
  4. 4 Hospital of Children and Adolescents and University of Helsinki;
  5. 5 Rigshospitalet and University of Copenhagen;
  6. 6 Illumina Inc.;
  7. 7 Uppsala University Children's Hospital

Abstract

To identify genes that are regulated by cis-acting functional elements in acute lymphoblastic leukemia (ALL) we determined the allele-specific expression (ASE) levels of 2529 genes by genotyping a genome-wide panel of SNPs in RNA and DNA from bone marrow and blood samples of 197 children with ALL. Using a reproducible, quantitative genotyping method and stringent criteria for scoring ASE, we found that 16% of the analyzed genes display ASE in multiple ALL cell samples. For most of the genes, the level of ASE varied largely between the samples, from 1.4-fold over-expression of one allele to apparent monoallelic expression. For genes exhibiting ASE, 55% displayed bi-directional ASE in which over-expression of either of the two SNP alleles occured. For bi-directional ASE we also observed overall higher levels of ASE and correlation with the methylation level of these sites. Our results demonstrate that CpG site methylation is one of the factors that regulates gene expression in ALL cells.

Footnotes

    • Received July 30, 2008.
    • Accepted October 27, 2008.

  • This manuscript is Open Access.

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  1. Published in Advance November 7, 2008, doi: 10.1101/gr.083931.108 Genome Res. gr.083931.108 Copyright © 2008, Cold Spring Harbor Laboratory Press

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