Molecular analysis of a gene affecting social cognition

描述（由申请人提供）：自闭症患者和9%的正常男性存在社会认知缺陷。一种x连锁基因EFHC2已在特纳综合症女性中被发现，其中30%的患者表现出类似自闭症的缺陷。关于EFHC2的功能我们一无所知。我们将首先解析EFHC2的等位基因、空间和时间表达模式。我们的下一个目标是确定EFHC2的正常性质。我们将解析EFHC2在神经元中的亚细胞位置，并测定Ca2+结合。我们的最终目标是确定EFHC2的哪种自然变异具有功能后果。我们将对特纳综合征患者的EFHC2位点进行测序，并通过基因分型和相关性分析来缩小功能snp的范围。我们将评估EFHC2变异对表达或钙结合的分子影响。我们的最终目标是评估神经递质释放是否受到与恐惧识别相关的EFHC2基因变异的影响。对影响社会认知的基因进行功能分析有助于理解自闭症，揭示正常的社会生理，并为解剖复杂的特征提供方法。

DESCRIPTION (provided by applicant): Deficits in social cognition are present in autism and 9% of otherwise normal males. An X-linked gene, EFHC2, has been mapped in women with Turner Syndrome, 30% of whom show autism-like deficits. Nothing is known about the function of EFHC2. We will first resolve the allelic, spatial, and temporal expression pattern of EFHC2. Our next aim will determine the normal properties of EFHC2. We will resolve the subcellular location of EFHC2 in neurons and assay Ca2+ binding. Our final aim is to determine which natural variation in EFHC2 has functional consequences. We will sequence the EFHC2 locus and narrow down functional SNPs by genotyping and analyzing association in Turner Syndrome patients. We will assess the molecular consequences of EFHC2 variation on expression or calcium binding. Our ultimate goals would be to evaluate whether neurotransmitter release is influenced by the genetic variation in EFHC2 associated with fear recognition. Functional analysis of a gene influencing social cognition could contribute to understanding autism, revealing normal social physiology, and developing methods for the dissection of complex traits.