Biological Determinants of Brain Variation in Autism

描述（由申请人提供）：这项拟议研究的目标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实现这一目标。我们首先利用我们现有的脑磁共振成像测量（传统的MRI容积法，脑连接，静息状态活动）的235个人，125自闭症和110个典型的发展科目，建立一个数据结构的大脑区域的利益，有至少50%的估计遗传典型的大脑，排序的大小，然后由组件的结构功能变异性。在我们的下一步中，我们询问全外显子组和全基因组序列和网络分析的分子通路的国家的最先进的分子遗传学方法在参考这个数据结构。我们期望这种对自闭症脑成像表型的变异性和极端性的详细分析将导致发现新的遗传关联，揭示新的生物学途径，并促进我们对自闭症神经病理学及其严重损害临床表现的理解。我们的研究结果将改变自闭症研究中的成像遗传学。

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.