Mammalian Molecular Genetics Group, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Hum Mol Genet. 2012 May 1;21(9):2086-101. doi: 10.1093/hmg/dds026. Epub 2012 Feb 3.
In addition to the genetic constitution inherited by an organism, the developmental trajectory and resulting mature phenotype are also determined by mechanisms acting during critical windows in early life that influence and establish stable patterns of gene expression. This is the crux of the developmental origins of health and disease hypothesis that suggests undernutrition during gestation and infancy predisposes to ill health in later life. The hypothesis that periconceptional maternal micronutrient supplementation might affect fetal genome-wide methylation within gene promoters was explored in cord blood samples from offspring of Gambian women enrolled into a unique randomized, double blind controlled trial. Significant changes in the epigenome in cord blood DNA samples were further explored in a subset of offspring at 9 months. Gender-specific changes related to periconceptional nutritional supplementation were identified in cord blood DNA samples, some of which showed persistent changes in infant blood DNA samples. Significant effects of periconceptional micronutrient supplementation were also observed in postnatal samples which were not evident in cord blood. In this Gambian population, the increased death rate of individuals born in nutritionally poor seasons has been related to infection and it is of interest that we identified differential methylation at genes associated with defence against infection and immune response. Although the sample size was relatively small, these pilot data suggest that periconceptional nutrition in humans is an important determinant of newborn whole genome methylation patterns but may also influence postnatal developmental patterns of gene promoter methylation linking early with disease risk.
除了生物体遗传的基因构成外，发育轨迹和由此产生的成熟表型也由早期生命关键窗口期发挥作用的机制决定，这些机制影响并建立了稳定的基因表达模式。这就是健康与疾病发育起源假说的核心，该假说认为妊娠和婴儿期的营养不良会导致以后的健康问题。在冈比亚妇女参与的一项独特的随机、双盲对照试验中，研究人员探索了围孕期母亲微量营养素补充是否会影响胎儿基因组范围内基因启动子的甲基化。在该试验的一部分 9 个月大的后代的脐带血样本中，进一步探索了脐带血 DNA 样本中表观基因组的显著变化。在脐带血 DNA 样本中发现了与围孕期营养补充有关的性别特异性变化，其中一些变化在婴儿血液 DNA 样本中持续存在。在产后样本中也观察到围孕期微量营养素补充的显著影响，而在脐带血中则没有明显的影响。在这个冈比亚人群中，营养较差季节出生的个体死亡率增加与感染有关，令人感兴趣的是，我们发现了与抗感染和免疫反应相关的基因的差异性甲基化。虽然样本量相对较小，但这些初步数据表明，人类围孕期营养是新生儿全基因组甲基化模式的重要决定因素，但也可能影响出生后基因启动子甲基化的发育模式，将早期与疾病风险联系起来。
