Genotype-Epigenotype Interaction at the IGF2 DMR.
Paternally expressed Insulin-like Growth Factor II (IGF2) encodes a gene whose protein product functions as a potent growth mitogen. Overexpression of IGF2 has been implicated in a wide number of disorders and diseases. IGF2 is regulated in part by differential methylation of the two parentally derived alleles. The differentially methylated region (DMR) located upstream of the imprinted promoters of IGF2 exhibits plasticity under environmental stress and is hypomethylated in several types of cancer. Through bisulfite pyrosequencing and confirmation by nucleotide sequencing, we discovered a CpG to CpC transversion that results in hypomethylation of one of the three CpGs comprising this DMR. The presence of the polymorphism introduces a genetic rather than an environmentally-driven epigenetic source of hypomethylation that is additive to non-genetic sources.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Box 91012, B223 LSRC Building, Durham, NC 27708, USA. susan.murphy@duke.edu.
Susan K
SK
Murphy
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Box 91012, B223 LSRC Building, Durham, NC 27708, USA. erin.erginer@gmail.com.
Erin
E
Erginer
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Box 91012, B223 LSRC Building, Durham, NC 27708, USA. zhiqing.huang@duke.edu.
Zhiqing
Z
Huang
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Box 91012, B223 LSRC Building, Durham, NC 27708, USA. zachary.visco@duke.edu.
Zachary
Z
Visco
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA. choyo@ncsu.edu.
Cathrine
C
Hoyo
CpG dinucleotide; Insulin-like Growth Factor II; differentially methylated region; hypomethylation; imprinted gene; polymorphism