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Stem Cell Reviews and Reports

, Volume 5, Issue 4, pp 328–333 | Cite as

Insights into the Regulation of a Common Variant of HMGA2 Associated with Human Height During Embryonic Development

  • Yvonne Tay
  • Sabrina Peter
  • Isidore Rigoutsos
  • Paulette Barahona
  • Sohail Ahmed
  • Peter Dröge
Short Report

Abstract

Early genetic studies in the mouse and chicken identified the HMGA oncogene as a candidate that regulates body height. Subsequent genome-wide SNP studies revealed a significant association of rs1042725 genotypes CT and CC in the 3’ UTR of HMGA2 with human height. Together, these studies indicated that HMGA2 expression levels during prenatal development might be a critical factor that contributes to the height phenotype. In the present study, we sought to gain insight into the regulation of HMGA2 during human embryonic development and provide evidence that the rs1042725 genotype is unlikely to affect HMGA2 levels in pluripotent human embryonic stem cells (hESCs). This implies that hESCs in the inner cell mass of blastocysts are most likely not involved in determining the human height phenotype associated with this SNP. By applying a computational approach and cell-based reporter assays, we then identified miR-196b as a candidate microRNA that could contribute to SNP-specific expression of HMGA2 during human prenatal development. We briefly discuss this result in the context of other known functions for miR-196b during vertebrate development.

Keywords

HMGA2 Human height Embryonic stem cells microRNA miR196-b 

Notes

Acknowledgements

This work was supported by the Singapore Academic research council (ARC) [grant number 90/07] and the National Medical Research Council (NMRC) [grant number 1114/2007] (PD), and SBIC-SSCC RPC-001/2007 (S.A.) We thank T. Stojanov and J. Shaft for advice and the provision of samples of SIVF hES cell lines.

Author Contributions

Y.T. performed qRT-PCR and miR analyses; S.P. performed genotyping and Western analyses; I. R. performed miR predictions; P.B. performed hES cell culture and genomic DNA preparation; S.H. supervised research; P.D. designed and supervised research, analyzed data, and wrote the paper.

Conflict of Interest

None

Supplementary material

12015_2009_9095_MOESM1_ESM.doc (31 kb)
Figure S1 (DOC 31 kb)

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Copyright information

© Springer Science + Business Media 2009

Authors and Affiliations

  • Yvonne Tay
    • 1
  • Sabrina Peter
    • 2
  • Isidore Rigoutsos
    • 3
  • Paulette Barahona
    • 4
  • Sohail Ahmed
    • 1
  • Peter Dröge
    • 2
  1. 1.Neural Stem Cells, Institute of Medical BiologyAgency for Science Technology and Research (A*STAR)SingaporeSingapore
  2. 2.Division of Genomics and Genetics, School of Biological SciencesNanyang Technological UniversitySingaporeSingapore
  3. 3.Bioinformatics and Pattern Discovery GroupIBM Thomas J. Watson Research CenterNew YorkUSA
  4. 4.Sydney IVFSydneyAustralia

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