Testing the DISC1 pathway for functional genetic variation and epistasis in major

测试主要功能遗传变异和上位性的 DISC1 通路

基本信息

批准号：
8599184
负责人：
William Richard McCombie
金额：
$ 73.32万
依托单位：
COLD SPRING HARBOR LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-16 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8599184
关键词：
Age of Onset Algorithms American Amino Acid Substitution Biological Bipolar Disorder Blood specimen Brain Cognition Complex Development Diagnosis Disease Drug Targeting Epigenetic Process Equilibrium Family Gene Expression Genes Genetic Genetic Epistasis Genetic Polymorphism Genetic Variation Genome Genotype Goals Individual Link Major Depressive Disorder Measures Mental Depression Mental Health Mental disorders Methylation Minor Moods Mutation National Institute of Mental Health Nature Pathway interactions Patients Pattern Phase Phenotype Proteins Psychiatric Diagnosis Public Health Recurrence Research Priority Risk Role Sample Size Sampling Scaffolding Protein Scanning Schizophrenia Signal Transduction Spectrum Analysis Testing Ursidae Family Variant case control genetic analysis genetic variant genome sequencing genome wide association study genome-wide member neurodevelopment novel public health relevance

项目摘要

DESCRIPTION (provided by applicant): Major depression is a serious psychiatric disorder impacting the lives of millions of Americans. The gene DISC1 has been linked to this disorder by translocation in a single Scottish family as well as being supported by functional analyses of the gene prominent in neural development. We propose to carry out whole genome sequencing on 40 members of the original translocation family to identify possible variants that modify the effec of the translocation on phenotype as well as examine epigenetic differences in those that bear the translocation. We will also carry out genetic analyses by both genotyping and targeted sequencing to look for genetic differences in DISC1 and its core pathway genes in a total of nearly 10,000 people. Lastly, we will examine blood samples from some of those individuals with variants in the core pathway to determine if these variants change gene expression.

描述（由申请人提供）：重度抑郁症是一种严重的精神疾病，影响着数百万美国人的生活。基因 DISC1 通过在一个苏格兰家族中的易位与这种疾病相关，并且得到了对神经发育中重要基因的功能分析的支持。我们建议对原始易位家族的 40 个成员进行全基因组测序，以确定可能改变易位对表型影响的变异，并检查携带易位的成员的表观遗传差异。我们还将通过基因分型和靶向测序相结合的方式进行遗传分析，寻找近万人中DISC1及其核心通路基因的遗传差异。最后，我们将检查核心途径中存在变异的一些个体的血液样本，以确定这些变异是否会改变基因表达。