Biological Determinants of Brain Variation in Autism

自闭症大脑变异的生物决定因素

基本信息

批准号：
9127805
负责人：
JANET Elizabeth LAINHART
金额：
$ 54.78万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
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：
2013-08-29 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9127805
关键词：
Affect Age Architecture Area Autistic Disorder Base of the Brain Behavioral Biological Biology Brain Brain imaging Brain region Characteristics Clinical Cognitive Communities Complex Copy Number Polymorphism Corpus Callosum DNA Sequence Databases Development Disease Ethnic Origin Family Family Study Genes Genetic Genetic Heterogeneity Genotype Goals Grouping Health Health Benefit Heritability High Prevalence Imagery Individual Inherited Knowledge Lead Magnetic Resonance Imaging Measurement Methods Molecular Molecular Genetics Multimodal Imaging Pathology Pathway Analysis Pathway interactions Pattern Phenotype Plumbing Preventive Intervention Probability Public Health Reporting Research Research Design Rest Role Solid Sorting - Cell Movement Source Structure Subgroup Taxonomy United States Variant base brain size data structure effective therapy exome gene discovery genetic association genetic variant genome sequencing imaging genetics interest member neuropathology novel proband risk variant tool white matter whole genome

项目摘要

DESCRIPTION (provided by applicant): The goal of this proposed research is to generate a genetic architecture of brain development. We aim to achieve this goal in two solid steps. We first utilize our existing brain MR imaging measurements (traditional MRI volumetry, brain connectivity, resting state activity) of 235 individuals, 125 with autism and 110 typically developing subjects, to build a data structure of brain regions of interest that have at least 50% estimated heritability for typical brains, sorted first by size and then by components of structura-functional variability. In our next step, we interrogate whole-exome and whole-genome sequences and network analysis of molecular pathways by state-of-the-art molecular genetics methods in reference to this data structure. We expect that this detailed analysis of variability and extremes in brain imaging phenotypes in autism will result in the discovery of new genetic associations that reveal new biological pathways and advance our understanding of autism neuropathology and its severely impairing clinical manifestations. Our results will thus change imaging genetics in autism research.

描述（由申请人提供）：这项拟议的研究的目的是产生大脑发育的遗传结构。我们的目标是通过两个坚实的步骤来实现这一目标。我们首先利用235个人，125名自闭症和110个通常会发展受试者的人的现有大脑MR成像测量（传统的MRI体积，大脑连接性，静止状态活动），构建感兴趣的大脑区域的数据结构，至少有50％的典型脑脑估计遗传性的遗传性，并以尺寸为单位和结构性可变性的组成部分。在下一步中，我们通过最先进的分子遗传学方法来审问全身和全基因组序列以及分子途径的网络分析，以参考这种数据结构。我们预计，自闭症中脑成像表型的可变性和极端的详细分析将导致发现新的遗传关联，这些遗传关联揭示了新的生物学途径并提高了我们对自闭症神经病理学及其严重损害的临床表现的理解。因此，我们的结果将改变自闭症研究中的成像遗传学。