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: 7322483
• 负责人: RONALD M ADKINS
• 金额: $ 18.62万
• 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/7322483
• 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

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：作为儿童的胎龄小小而出生的人面临严重的健康问题，并且随着基本高血压，心血管疾病，2型糖尿病和与妊娠有关的高血压和与妊娠有关的高血压和糖尿病的风险增加。对胎儿生长率有重大遗传影响。印记的基因使从母亲或父亲继承的等位基因在某些胎儿组织或胎儿发育的某些阶段不表达，这是这种遗传影响的主要部分。目的：通过直接母体遗传效应，产物父母（印迹）效应或直接的胎儿基因型效应来确定与妊娠年龄大小变化相关的8个印迹基因组区域的变化。假设：1）妊娠年龄的大小受遗传父母或直接归因于印迹基因座的直接母体遗传效应的影响。 2）胎儿单核苷酸多态性（SNP）与胎龄单独或组合（单倍型）有关。不可思议的区域：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，生长因子受体结合的蛋白10（GRB10），鸟嘌呤核苷酸核苷酸核苷酸结合蛋白，α-结合蛋白，α-刺激（GNAS）和Chromososom刺激（GNAS）和11p15和11p17Q3222222Q32。设计：500（250个非裔美国人和高加索人）将在妊娠时代随机招募母亲新生三重奏。严格的包容性排斥标准将最大程度地减少对出生体重变化的非基因贡献者，并富集遗传成分。单核苷酸多态性（SNP）的变化将在三重奏和用于鉴定遗传影响遗传学年龄的遗传影响的三重奏和复杂的分析技术中确定，可归因于母体遗传变异，烙印（“父母 - 原始”）和新生儿遗传变异。分析将控制许多已知或潜在的胎儿大小相关，例如性别，胎龄，母体BMI和奇偶校验。与公共卫生有关：检测胎儿偏见的胎儿的能力对于妊娠而言，他们也可能表现出越来越多的成年后慢性病倾向，这将允许实施干预方法，以促进胎儿生长或改善胎儿生长限制的长期后果。例如，改变甲基供体的可及性的饮食干预措施在小鼠模型中表现出了希望。