Genetic Analysis of Noise Phobia

描述（由申请人提供）：本开发/探索性申请旨在探索噪音恐惧症（家犬常见的行为障碍）的遗传基础。狗是确定行为遗传基础的极好模型系统。犬基因组学的最新进展意味着对犬行为特征进行严格遗传分析的工具已经到位。自然发生的焦虑综合征，类似于人类中发现的许多症状，在狗中很常见，并且通常在家庭中分离。焦虑症包括大部分犬行为病理，因此在犬患者群体中可清楚识别。为了我们的具体目标，我们计划在两个纯种犬中使用系谱和病例对照样本进行犬噪音恐惧症的遗传分析。我们将从一个扩展的边境牧羊犬噪音恐惧症谱系的~60名成员中的狗以及两个放牧品种边境牧羊犬和澳大利亚牧羊犬中的~50对无关的噪音恐惧症病例和对照中获得DNA样本。我们将使用一个详细的和临床验证的行为问卷来确定噪音恐惧症的表型，然后用全基因组SNP标记进行基因分型。将对家族样本进行连锁分析，并对病例对照样本进行关联分析。在有限数量的相关品种中成功分析犬的复杂行为表型，将为在众多品种中对犬行为表型进行更雄心勃勃的评估提供依据。此外，将这些发现转化为人类焦虑症研究将得到促进。公共卫生相关性：了解狗的噪音恐惧症，利用家犬独特的遗传结构及其与人类的行为相似性，可以为人类焦虑症的精神病学研究提供信息。阐明病理行为背后的生物系统将提高我们对行为的潜在分子生物学的总体理解，使狗能够为这个快速发展的领域做出贡献。

DESCRIPTION (provided by applicant): This Developmental/Exploratory application proposes to explore the genetic basis of noise phobia, a common behavioral disorder in the domestic dog. The dog is an excellent model system for determining the genetic bases of behavior. Recent advances in canine genomics mean that the tools are in place for rigorous genetic analyses of canine behavioral traits. Naturally occurring anxiety syndromes, similar to many found in humans, are common in dogs, and often segregate in families. Anxiety disorders comprise the bulk of canine behavioral pathologies, and as such are clearly recognizable in canine patient populations. For our specific aims, we plan to carry out genetic analyses of canine noise phobia using pedigrees and case control samples in two pure breeds. We will obtain DNA samples from dogs among the ~60 members of an extended Border Collie noise phobia pedigree, as well as ~50 pairs of unrelated noise phobia cases and controls in each of two herding breeds, Border Collies and Australian Shepherds. We will determine the noise phobia phenotype using a detailed and clinically verified behavioral questionnaire, followed by genotyping with genome-wide SNP markers. Linkage analyses will be carried out with the family sample, and association analyses performed with the case-control sample. Successful analysis of a complex behavioral phenotype in the dog in a limited number of related breeds will provide the rationale for a more ambitious assessment of canine behavior phenotypes across numerous breeds. Additionally, translation of these findings into human anxiety disorder research will be facilitated. PUBLIC HEALTH RELEVANCE: Understanding noise phobia in dogs, taking advantage of the unique genetic structure of the domestic dog, and its behavioral similarities to humans may inform psychiatric research on human anxiety disorders. Elucidation of the biological systems underlying pathological behavior will heighten our general understanding of the underlying molecular biology of behavior, allowing the dog to contribute to this rapidly evolving field.