Genetic characterization of the Drosophila homologue of coronin

10.1242/jcs.01034Journal of Cell Science117101911-192

Effects of Aminoglycoside Antibiotics on Human Embryonic Stem Cell Viability during Differentiation in Vitro

10.1155/2017/2451927Stem Cells International2017245192

Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range

10.1186/1471-2164-12-509BMC Genomics1250

Oncogenic transformation of human mammary epithelial cells by autocrine human growth hormone

Cancer Research651317-324CNRE

Identification of early indicators of altered metabolism in normal development using a rodent model system

10.1242/dmm.031815DMM Disease Models and Mechanisms1133181

Abstract. Epigenetic marks at birth predict childhood body composition at age 9 years

Objective: While genomic variation explains only a modest proportion of the risk of cardiovascular and metabolic disease, animal models demonstrate that maternal environmental influences alter epigenetic processes in the offspring, with important effects on their later body composition and cardiometabolic function. Whether such processes operate in humans has not been examined.Methods: Using DNA extracted from stored umbilical cord tissue from healthy neonates who were subsequently extensively phenotyped, we related the DNA methylation status of specific CpGs 5’ from candidate genes to body composition measured by DXA scanning at age 9 years. Appropriate institutional ethics committee clearance and participants’ informed consent were obtained.Results: Methylation, measured by the Sequenom MassARRAY system, varied greatly at particular CpG sites. Of 68 CpGs studied, 31 had a median methylation >5% and a 5-95% range >10%. Independently of sex, there were strong correlations of the degree of methylation in specific CpGs in eNOS with childhood fat mass (Pearson correlation rp 50.42, n566) and trunk/limb fat ratio (rp 50.33, n566), and in RXRA methylation with fat mass and percentage fat mass (rp 50.32 and 0.29, respectively, n564) (all p,0.005, taking account of methylation at other CpG sites). Methylation at these sites was not linked to birth weight. Controlling for sex, perinatal epigenetic marks explained more than 40% of the variance in body composition at age 9 years.Conclusions: Epigenetic marks at birth predict a significant proportion of the variance in later childhood adiposity, indicating that substantial components of later metabolic disease risk are induced before birth. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later chronic non-communicable disease. MAH and JSJ are supported by the British Heart Foundation. PDG and AS are funded by the National Research Centre for Growth and Development (New Zealand). BSE is supported by the Agency for Science, Technology and Research (Singapore). This work was supported by the charity WellChild (previously Children Nationwide), by the University of Southampton, by the UK Medical Research Council and the EpiGen consortium