Effect of FADS gene variants on fatty acid synthesis & brain development in India

FADS基因变异对脂肪酸合成的影响

基本信息

批准号：
8211534
负责人：
FLOYD H CHILTON
金额：
$ 12.77万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-06 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8211534
关键词：
Academy Adult Africa African Age Alleles Animals Arachidonic Acids Area Attention Attention deficit hyperactivity disorder Autistic Disorder Behavioral Biochemical Markers Biochemistry Bipolar Disorder Blood Circulation Brain Central America Child Cities Cognitive Collaborations Country DNA Data Dental Developing Countries Development Diet Disease Docosahexaenoic Acids Doctor of Philosophy Embryo Environment European Eye Development Face Fatty Acids Fatty acid glycerol esters Fetus Food Food Analysis Frequencies Future Gene Cluster Gene Frequency Genetic Markers Genetic Variation Genomics Genotype Health Sciences Human Human Development Hyperactive behavior India Infant Institutes Laboratories Malnutrition Medical Medium chain fatty acid Mental disorders Methods Molecular Mothers Mutation Nutritional Nutritional status Oils Pattern Photoreceptors Plant Oils Plants Polyunsaturated Fatty Acids Population Preparation Public Health Religion and Spirituality Research Research Infrastructure Research Personnel Science Scientist South America Southeastern Asia Synapses Techniques Technology Therapeutic Training Training and Infrastructure Universities Visual base blood lipid combat dietary supplements early childhood fatty acid biosynthesis fetal forest medical schools nervous system disorder nutrition pregnant pressure programs sample fixation

项目摘要

DESCRIPTION (provided by applicant): Long-chain polyunsaturated fatty acid (LC-PUFA), such as docosahexaenoic acid (DHA) and arachidonic acid (AA) are vital for brain and eye development. Specifically, normal visual and cognitive development is dependent on an adequate supply of DHA and AA in synapses and photoreceptors. Additionally, a lack of LC- PUFAs or an imbalance between I-3 and I-6 fatty acids, has been associated with a number of behavioral abnormalities, as well as neurological and psychiatric disorders in both children and adults, particularly attention-deficit hyperactivity (ADHD) and autism spectrm disorders, and unipolar and bipolar disorders. Pregnant mothers and their developing fetuses as well as young children who are impacted by malnutrition are particularly vulnerable because the staple foods they ingest have little or no preformed DHA or AA. Under such circumstances, the amount of LC-PUFAs found in circulation depends on that which can be synthesized from medium chain plant-based fatty acids (MC-FA). Studies from Dr. Chilton's laboratory in collaboration with Drs. Rasika Mathias and Kathleen Barnes at Johns Hopkins University School of Medicine have utilized DNA from the 52 populations described in the Human Diversity Panel and found that there are dramatic differences in populations with regard to those which contain alleles associated with efficient conversion of MC-FA to LC- PUFAs. Specifically, our data reveal that India sits geographically between populations to the east that have the alleles that facilitate the conversion of MC-FAs to LC-PUFAs and populations to the west of that have little capacity for conversion. Given, the high number of children exposed to malnutrition within India, it is vital to understand the distribution of alleles that impact LC-PUF synthesis throughout India. The objective of the current R-21 proposal is to initially establish a collaborative research program between Wake Forest University Health Sciences (WFUHS) and NITTE University/AB Shetty Memorial Institute of Dental Sciences (ABSMIDS)/K.S. Hegde Medical Academy (KSHEMA), Mangalore, India to put in place the infrastructure to analyze fatty acid nutritional status circulating fatty acid levels and allele frequencies in the FADS gene cluster in populations in the coastal city of Mangalore in the State of Karnataka in Southern India. Simultaneously in preparation for a more significant program for analyzing DNA and circulating fatty acids in large population centers of India (a subsequent R01), we will provide training mechanisms for investigators and PhD candidates from the Department of Biochemistry at NITTE University, KSHEMS and ABSMIDS, Mangalore, India in the areas of public health aspects of human genomics, nutrition and the consequences of impaired brain development, in the molecular and statistical techniques necessary to examine SNPs, genotypic/phenotypic associations and in methods involved in the analysis of food and blood lipids focusing on fatty acids. Together this will create a fertile local academic environment and a proven infrastructure needed to better understand how diverse Indian populations synthesize fats that are critical for brain and eye development. PUBLIC HEALTH RELEVANCE: Malnutrition is a major public health problem among infants and young children in Southeast Asia, especially India. We propose to train Indian scientist to use a combination of genetic and biochemical markers to understand how the diverse Indian populations make fats and the nutritional fatty acid requirements that are important in brain and eye development, in order combat fat malnutrition in a country that has 1/3 of the 150 million malnourished children in the world.

描述（由申请人提供）：长链多不饱和脂肪酸（LC-PUFA），例如Docosahexaenoic Acid（DHA）和花生四烯酸（AA）（AA）对于大脑和眼睛发育至关重要。具体而言，正常的视觉和认知发展取决于突触和光感受器中DHA和AA的足够供应。此外，I-3和I-6脂肪酸之间缺乏LC-PUFA或不平衡，与儿童和成人的许多行为异常以及神经和精神疾病有关，尤其是注意力缺陷多动（ADHD）和自闭症异常疾病和自闭症疾病和Uniporlm and Bipolar and Bipolar and Bipolar和Bipolar disorlorsers中的神经和精神疾病。怀孕的母亲及其发展中的胎儿以及受营养不良影响的幼儿特别脆弱，因为他们摄入的主食几乎没有或没有预先形成的DHA或AA。在这种情况下，循环中发现的LC-PUFA的量取决于可以从中链植物性脂肪酸（MC-FA）中合成的液晶量。 Chilton博士的实验室与Drs合作的研究。约翰·霍普金斯大学医学院的Rasika Mathias和Kathleen Barnes利用了人类多样性小组中描述的52个人群中的DNA，发现人群在包含与MC-FA相关的等位基因相关的等位基因的人群中存在巨大差异。具体而言，我们的数据表明，印度在东方人口之间的地理位置上坐着，这些等位基因有助于将MC-FAS转换为LC-PUFAS和人群向西的转化，而该等位基因几乎没有转换的能力。鉴于，印度境内暴露于营养不良的儿童数量很大，了解影响整个印度LC-PUF合成的等位基因的分布至关重要。当前R-21提案的目的是最初建立一个 Wake Forest University Health Sciences（WFUHS）与Nitte University/AB Shetty纪念科学研究所（Absmids）/K.S之间的合作研究计划。印度芒格洛尔的Hegde医学院（KSHEMA）建立了基础设施，以分析沿海地区卡纳塔克省沿海城市曼加罗尔州曼加罗尔州曼加罗尔州曼加罗尔州曼加罗尔州曼加罗尔市的脂肪酸营养状况循环脂肪酸水平和等位基因频率。 Simultaneously in preparation for a more significant program for analyzing DNA and circulating fatty acids in large population centers of India (a subsequent R01), we will provide training mechanisms for investigators and PhD candidates from the Department of Biochemistry at NITTE University, KSHEMS and ABSMIDS, Mangalore, India in the areas of public health aspects of human genomics, nutrition and the consequences of impaired brain development,在检查SNP，基因型/表型关联以及参与分析脂肪酸的食物和血脂分析所需的分子和统计技术中。这将共同创造一个肥沃的当地学术环境，并建立一个可靠的基础设施，以更好地理解印度种群如何综合对大脑和眼睛发育至关重要的脂肪。公共卫生相关性：营养不良是东南亚，尤其是印度的婴儿和幼儿的主要公共卫生问题。我们建议培训印度科学家使用遗传和生化标志物的结合，以了解印度多样化的人群如何制造脂肪和在大脑和眼睛发育中很重要的营养脂肪酸需求，以便在世界上拥有1.5亿个熟食儿童中的1/3个国家中的战斗脂肪营养不良。