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

母胎冲突：印记基因对胎儿生长的影响

• 批准号: 7488476
• 负责人: RONALD M ADKINS
• 金额: $ 18.24万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7488476
• 关键词: 11p15; Adult; Affect; African American; Age-Years; Alleles; Biological Markers; Birth Weight; Cardiovascular Diseases; Caucasians; Caucasoid Race; Cessation of life; Child; Chronic Disease; Clinical; Conflict (Psychology); Development; Diabetes Mellitus; Dietary Intervention; Disease; Essential Hypertension; Ethnic Origin; Exclusion Criteria; Exhibits; Face; Fathers; Female; Fetal Development; Fetal Growth; Fetal Growth Retardation; Fetal Tissues; Fetus; Gender; Genes; Genetic; Genetic Variation; Genomic Imprinting; Gestational Age; Gestational Diabetes; Goals; Growth; H19 gene; Haplotypes; Health; Human; Hypertension; Individual; Inherited; Insulin; Insulin-Like Growth Factor II; Intervention; Knowledge; Life; Low Birth Weight Infant; Mammals; Methods; Mothers; Neonatal; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Parents; Pattern; Predisposition; Pregnancy; Public Health; Rate; Recruitment Activity; Regulation; Risk; Single Nucleotide Polymorphism; Small for Gestational Age Infant; Staging; Surveys; Techniques; Testing; Triad Acrylic Resin; Variant; base; cost; design; fetal; fitness; growth factor receptor-bound protein 10; guanine nucleotide binding protein; human IGF2R protein; imprint; male; maternal imprint; mouse model; parental influence; parity; size

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 is a substantial genetic influence on the rate of fetal growth. Genes that are imprinted such that the allele inherited from the mother or the father is not expressed in some fetal tissues or at some stages of fetal development are a major part of this genetic influence. Objective: Identify variation in 8 imprinted genomic regions that are associated with variation in size for gestational age, via direct maternal genetic effects, parent-of-origin (imprinting) effects or direct fetal genotypic effects. Hypotheses: 1) Size for gestational age is influenced by parent-of-origin or direct maternal genetic effects attributable to imprinted loci. 2) Fetal single nucleotide polymorphisms (SNPs) are associated with size for gestational age individually or in combinations (haplotypes). Imprinted regions: Insulin (INS), insulin-like growth factor 2 (IGF2), insulin-like growth factor 2 receptor (IGF2R), H19, growth factor receptor-bound protein 10 (GRB10), guanine nucleotide-binding protein, alpha- stimulating (GNAS), and chromosomal regions 7q32 and 11p15. Design: 500 (250 each of African-Americans and Caucasians) mother-father-newborn trios will be recruited randomly across the spectrum of size for gestational age. Stringent inclusion-exclusion criteria will minimize non-genetic contributors to birth weight variation and enrich for the genetic component. Variation at single nucleotide polymorphisms (SNPs) will be determined in the trios and sophisticated analytical techniques used to identify genetic influences on size for gestational age attributable to maternal genetic variation, imprinting ("parent-of-origin"), and newborn genetic variation. Analyses will control for a number of known or potential correlates of fetal size, such as gender, gestational age, maternal BMI, and parity. Relevance to Public Health: The ability to detect fetuses predisposed to being born small for gestational who may also exhibit increased predisposition to chronic illnesses in adulthood will allow for the implementation of intervention methods that may facilitate fetal growth or ameliorate the long-term consequences of fetal growth restriction. For example, dietary interventions that alter the accessibility of methyl donors have shown promise in mouse models.

胎龄小的人面临儿童的严重健康问题，并增加风险 基本高血压，心血管疾病，2型糖尿病和与妊娠有关的成年人 高血压和糖尿病。对胎儿生长率有重大遗传影响。基因 被印记在于，从母亲或父亲继承的等位基因在某些胎儿中没有表达 组织或胎儿发育的某些阶段是这种遗传影响的主要部分。 目的：确定与大小差异相关的8个印迹基因组区域的变化 胎龄，通过直接母体遗传效应，父母 - 烙印（印迹）效应或直接胎儿 基因型效应。 假设：1）妊娠年龄的大小受父母的影响或直接母体遗传的影响 归因于印迹基因座的效果。 2）胎儿单核苷酸多态性（SNP）与 胎龄单独或组合（单倍型）的大小。 印迹区域：胰岛素（INS），胰岛素样生长因子2（IGF2），胰岛素样生长因子2受体 （IGF2R），H19，生长因子受体结合蛋白10（GRB10），鸟嘌呤核苷酸结合蛋白，α- 刺激（GNA）和染色体区域7q32和11p15。 设计：500（250名非裔美国人和高加索人）将是母亲 - 纽伯恩三人组 在胎龄范围内随机招募。严格的包容性排斥标准将 最大程度地减少对出生体重变异的非遗传因素，并丰富遗传成分。变化 单核苷酸多态性（SNP）将在三重奏和复杂的分析中确定 用于识别遗传年龄的遗传影响的技术，可归因于母体遗传 变异，烙印（“原产父母”）和新生儿遗传变异。分析将控制多个 胎儿大小的已知或潜在相关性，例如性别，胎龄，母体BMI和奇偶校验。 与公共卫生的相关性：检测胎儿易于出生的胎儿的能力 在成年期间也可能表现出对慢性疾病的倾向增加的人 实施可能促进胎儿生长或改善长期的干预方法 胎儿生长限制的后果。例如，改变可访问性的饮食干预措施 甲基供体在小鼠模型中表现出了希望。