Genomics and Epigenomics of Fetal Growth Regulation

出生时小于胎龄的人在儿童时期就面临严重的健康问题， 成年后患高血压、心血管疾病、2型糖尿病和 妊娠高血压和糖尿病。基因对胎儿的影响有两种类型 生长：1)DNA序列变化(单核苷酸多态)和2)增加 DNA主干上的甲基(表观遗传学)。表观遗传变化似乎是强烈的 受已知关键营养素摄入的影响。这项研究的最终目标是 了解哪些基因变异和营养物质会增加婴儿低出生的风险 体重，以及如何通过医疗、营养或 药物干预。 目的：在整个基因组中，单核苷酸多态和 DNA甲基化将被调查，并与低出生体重的风险有关。另外， 孕妇在关键营养素摄入量上的差异将与 他们新生儿的DNA甲基化模式。 假设：1)出生体重的变化与单核苷酸模式有关 多态和拷贝数变异。2)出生体重的变化与模式有关 DNA甲基化的基因。3)DNA甲基化模式的变化与 母亲摄入的营养物质参与了导致DNA甲基化的途径。 设计：将收集800对母婴和另外500对母婴的DNA- 新生儿三人组。严格的纳入-排除标准将最大限度地减少非遗传因素 出生体重变化和丰富的遗传/表观遗传成分。商业“筹码” 将用于研究单核苷酸多态和DNA的全基因组模式 甲基化变异。将使用问卷调查来确定关键营养素的摄入量。 将进行统计分析，以检验这三个假设。 注：与最初的摘要相比，唯一的变化是从1000个母亲新生儿改为800个母亲新生儿 成对的。

Individuals born small for gestational age face severe health problems as children and increased risks as adults of essential hypertension, cardiovascular disease, type 2 diabetes and pregnancy-related hypertension and diabetes. There are two types of genetic influences on fetal growth: 1) changes in DNA sequence (single nucleotide polymorphisms) and 2) addition of methyl groups to the DNA backbone (epigenetics). Epigenetic changes appear to be strongly influenced by the consumption of known key nutrients. The ultimate goals of this research are to understand what genetic variants and nutrients increase the risk of a baby being low birth weight and how it may be possible to reduce these risks with medical, nutritional, or pharmacological interventions. Objective: Across the entire genome, variation due to single nucleotide polymorphisms and DNA methylation will be surveyed and related to the risk of low birth weight. Additionally, variation among pregnant women in the consumption of key nutrients will be related to the patterns of DNA methylation in their newborns. Hypotheses: 1) Variation in birth weight is associated with patterns of single nucleotide polymorphism and copy number variation. 2) Variation in birth weight is associated with patterns of DNA methylation. 3) Variation in DNA methylation patterns is correlated with variation in maternal intake of nutrients involved in the pathways leading to DNA methylation. Design: DNA will be collected for 800 mother-newborn pairs and an additional 500 motherfather- newborn trios. Stringent inclusion-exclusion criteria will minimize non-genetic contributors to birth weight variation and enrich for the genetic/epigenetic component. Commercial “chips” will be used to survey genome-wide patterns of single nucleotide polymorphism and DNA methylation variation. Questionnaires will be used to determine the intake of key nutrients. Statistical analyses will be performed to test the three hypotheses. Note: The only change from the original abstract is a change from 1,000 to 800 mothernewborn pairs.