Maternal-Fetal Conflict: The Effect of Imprinted Genes on Fetal Growth

小于胎龄儿出生的个体， 疾病，包括高血压、心血管疾病 疾病、2型糖尿病和妊娠相关高血压和糖尿病。两 传统遗传学和表观遗传学在胎儿生长调节中起主要作用。 这些基因是有印记的，这意味着要么是母系的，要么是 父系遗传的等位基因在一些或所有组织中沉默，具有大的 影响胎儿生长的调节。事实上，人们认为， 导致了印记基因之间的统一模式， 生长抑制基因座和生长促进基因座的母体等位基因是 沉默（Silenced）印记基因座的主要机制之一是 在亲本之一上的CpG二核苷酸上大量添加甲基 等位基因基于对模式生物的观察， 胎儿的DNA会受到母亲营养摄入的显著影响 参与代谢途径。这项研究的直接目标是 确定遗传（胎儿、母体和原始父母）和表观遗传影响 对胎儿生长的影响最终的目标是能够预测那些 倾向于小于胎龄，并确定如何减少 药物、营养或药物干预的风险。目的： 在基因组的所有印记区域中， 单核苷酸多态性（SNPs）在500名母亲-父亲-新生儿三人组和DNA 这些新生儿的甲基化，并确定母亲的营养摄入量 怀孕期间DNA甲基化的关键。假设：1）出生变异 体重是由于a）直接母体，B）直接胎儿和/或c）亲本来源 （印记）遗传效应。2)出生体重的变化与 印迹基因中的DNA甲基化模式。3)DNA甲基化变异 模式与母亲营养素摄入量的变化相关， 过程设计：从500组母亲、父亲和他们的孩子身上收集DNA。 根据严格的纳入/排除标准对新生儿进行评估。标记SNP和 那些以前与印记基因组中肥胖相关特征相关的基因 将对各地区进行调查。在所有印迹基因组区域DNA甲基化 模式将在差异甲基化区域和印迹中确定。 控制区域。怀孕期间和刚怀孕后的饮食调查仪器 将用于确定母亲对DNA甲基化至关重要的营养素的摄入。 将进行统计分析，以检验这三个假设。

Individuals born small for gestational age have increased risks of serious illness as newborns and throughout life, including hypertension, cardiovascular disease, type 2 diabetes and pregnancy-related hypertension and diabetes. Both traditional genetics and epigenetics play a major role in fetal growth regulation. Genes that are imprinted, meaning that either the maternally- or paternally-inherited allele is silenced in some or all tissues, have a large influence on the regulation of fetal growth. Indeed, it is thought that selection has led to the uniform pattern among imprinted genes that the paternal allele of growth- retarding loci and the maternal allele of growth-promoting loci are imprinted (silenced). One of the main mechanisms for imprinting a locus is the extensive addition of methyl groups to CpG dinucleotides on one of the parental alleles. Based on observations in model organisms, the extent of methylation of fetal DNA can be dramatically influenced by the mother's intake of nutrients involved in that metabolic pathway. The immediate goal of this research is to identify genetic (fetal, maternal, and parent-of-origin) and epigenetic influences on fetal growth. The ultimate goals are to be able to anticipate those fetuses that are predisposed to being small for gestational age and to determine how to reduce that risk with medical, nutritional, or pharmacological interventions. Objectives: In all imprinted regions of the genome, survey patterns of variation in DNA sequence (single nucleotide polymorphisms; SNPs) in 500 mother-father-newborn trios and DNA methylation in those newborns and determine the maternal intake of nutrients essential to DNA methylation during pregnancy. Hypotheses: 1) Variation in birth weight is due to a) direct maternal, b) direct fetal and/or c) parent-of- origin (imprinting) genetic effects. 2) Variation in birth weight is associated with patterns of DNA methylation in imprinted genes. 3) Variation in DNA methylation patterns is correlated with variation in maternal intake of nutrients key to that process. Design: DNA is being collected from 500 sets of mothers, fathers, and their newborns based on stringent inclusion/exclusion criteria. Both tagging SNPs and those previously associated with obesity- related traits in imprinted genomic regions will be surveyed. Across all imprinted genomic regions DNA methylation patterns will be determined in differentially methylated regions and imprinting control regions. Dietary survey instruments during pregnancy and just afterwards will be used to determine the maternal intake of nutrients vital to DNA methylation. Statistical analyses will be performed to test the three hypotheses.