Genetics and genomics of human breast milk composition

人类母乳成分的遗传学和基因组学

• 批准号: 10431621
• 负责人: KELSEY ELIZABETH JOHNSON
• 金额: $ 0.25万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10431621
• 关键词: Address; Adult; Antibodies; Biological; Biological Assay; Biological Testing; Biology; Biopsy; Blood Circulation; Body mass index; Breast Feeding; Cells; Cellular biology; Characteristics; Child; Childhood; Cities; Clinical; Colostrum; Communities; Community Health; Computational Biology; Core Facility; Data; Development; Epidemiologic Methods; Epidemiology; Epithelial Cells; Exclusive Breastfeeding; Factor Analysis; Fatty Acids; Foundations; Future; Gene Expression; Genes; Genetic; Genetic Determinism; Genomic DNA; Genomic approach; Genomics; Genotype; Growth; Growth Factor; Health; Health Benefit; Human; Human Milk; Human Subject Research; Immune; Immune system; Individual; Infant; Infant Health; Institution; Interdisciplinary Study; Intervention; Knowledge; Lactation; Leukocytes; Life; Link; Mammary gland; Maps; Maternal Health; Metabolic; Milk; Minnesota; Modification; Molecular; Molecular Analysis; Mothers; Multiomic Data; Nutritional status; Oligosaccharides; Outcome; Pathway interactions; Phenotype; Physiological; Play; Postpartum Period; Probiotics; Quantitative Trait Loci; RNA Sequences; Research; Resources; Role; Sampling; Shapes; Stains; System; Techniques; Testing; Time; Tissues; Training; Translational Research; Twin Multiple Birth; Universities; Variant; Woman; antimicrobial peptide; career; cell type; data integration; genetic variant; genome-wide; host microbiome; improved; infant gut microbiome; maternal obesity; microbiome; milk microbiome; milk production; multiple omics; neonate; novel; nutrition; responsible research conduct; single-cell RNA sequencing; skills; tool

Project Summary Breastfeeding plays a critical role in infant and maternal health; however, the components of milk underlying the health effects of milk and consequences of variation in milk composition are not well understood. Except for a few milk components, the role of maternal genetics in milk composition is largely unknown, limiting the epidemiological tools available to tease apart the effects of variation in milk composition on infant and maternal health. Thus, enhancing our understanding of the genetic and genomic basis of variation in milk composition is critical for identifying the mechanisms linking breastfeeding to infant and maternal health outcomes. One such outcome is the infant gut microbiome, for which breastfeeding is a primary determinant, with implications for the nascent immune system and the child’s long-term metabolic health. This proposal contains a comprehensive analysis of the molecular and cellular composition of breast milk, the effect of maternal genetics on this composition, and the impact of host-microbiome interactions in milk on the infant gut microbiome. The results will provide foundational data for advancing milk research and help advance our knowledge of human nutrition during the critical first 1000 days of life. Three specific aims will address these priorities by (1) applying single cell RNA-seq to assess the cellular composition of milk at two time points in lactation, thus profiling changes in gene expression in the mammary gland across lactation and the maternal immune cells that provide critical immune support to the neonate; (2) identifying genetic variants associated with gene expression in milk (eQTLs) and cell type-eQTL interactions in milk; and (3) applying multi-omic data integration to milk gene expression, the milk microbiome, and infant gut microbiome to uncover the biological pathways underlying shared variation across these systems, and to assess the impact of maternal metabolic health on these pathways. Each Aim will leverage cutting edge genomics techniques never previously applied to human milk to expand our understanding of the genetic and genomic basis of milk composition. Research will take place at the University of Minnesota – Twin Cities, a major research institution, with state-of-the-art core facilities for genomics and clinical/translational research. The trainee will receive training in the biology of milk and lactation, computational biology, human subjects research, and responsible conduct of research from an interdisciplinary sponsorship team in the departments of Epidemiology & Community Health and Genetics, Cell Biology and Development. This training plan will result in the trainee acquiring the skills and a scientific foundation to launch her independent academic career.

项目摘要 母乳喂养在婴儿和孕产妇健康方面发挥着关键作用;然而， 牛奶对健康的影响和牛奶成分变化的后果还没有得到很好的理解。除了 由于母乳成分很少，母体遗传学在母乳成分中的作用在很大程度上是未知的， 现有的流行病学工具可以区分牛奶成分变化对婴儿和母亲的影响 健康因此，提高我们对牛奶成分变异的遗传和基因组基础的理解， 这对于确定母乳喂养与婴儿和产妇健康结果之间的联系机制至关重要。一个这样 结果是婴儿肠道微生物组，母乳喂养是主要决定因素， 新生的免疫系统和孩子的长期代谢健康。该提案包含一个 综合分析母乳的分子和细胞组成， 遗传学对这种成分的影响，以及牛奶中宿主-微生物组相互作用对婴儿肠道的影响 微生物组这些结果将为推进牛奶研究提供基础数据，并有助于推进我们的研究。 在生命的关键的前1000天的人类营养知识。三个具体目标将解决这些问题 优先事项包括：（1）应用单细胞RNA-seq在两个时间点评估牛奶的细胞组成 哺乳期，从而分析哺乳期和母体乳腺中基因表达的变化。 为新生儿提供关键免疫支持的免疫细胞;（2）识别相关的遗传变异 与牛奶中的基因表达（eQTL）和牛奶中的细胞类型-eQTL相互作用;以及（3）应用多组学数据 整合到牛奶基因表达，牛奶微生物组和婴儿肠道微生物组，以揭示生物学 这些系统之间共享变异的潜在途径，并评估母体代谢的影响。 健康在这些道路上。每一个目标都将利用以前从未应用过的尖端基因组技术 母乳的研究，以扩大我们对母乳成分的遗传和基因组基础的理解。研究 将在明尼苏达大学双城分校举行，这是一个主要的研究机构，拥有最先进的 基因组学和临床/转化研究的核心设施。受训者将接受生物学方面的培训， 牛奶和哺乳，计算生物学，人类受试者研究，以及负责任的研究行为， 流行病学与社区卫生和遗传学系的跨学科赞助团队， 细胞生物学与发育该培训计划将使受训者获得技能和科学的 基金会，以启动她的独立学术生涯。