title: Insights into the regulation of a common variant of HMGA2 associated with human height during embryonic development.
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.
authors.affiliation: Neural Stem Cells, Institute of Medical Biology, Agency for Science Technology and Research (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Tay
authors.forename: Sabrina
authors.initials: S
authors.lastname: Peter
authors.forename: Isidore
authors.initials: I
authors.lastname: Rigoutsos
authors.forename: Paulette
authors.initials: P
authors.lastname: Barahona
authors.forename: Sohail
authors.initials: S
authors.lastname: Ahmed
authors.forename: Peter
authors.initials: P
authors.lastname: Dröge
mesh_terms: D000818:Animals; D001483:Base Sequence; D001827:Body Height; D002460:Cell Line; D004622:Embryo, Mammalian / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D025743:HMGA2 Protein; C542543:MIRN196 microRNA, human; D035683:MicroRNAs