Genetic Analysis of Noise Phobia

描述（由申请人提供）：本发展/探索性申请旨在探索噪音恐惧症的遗传基础，这是一种常见的家养狗的行为障碍。在确定行为的遗传基础方面，狗是一个极好的模型系统。犬类基因组学的最新进展意味着对犬类行为特征进行严格的基因分析的工具已经到位。自然产生的焦虑综合症，类似于人类的许多症状，在狗身上很常见，而且往往在家庭中分离。焦虑障碍是犬类行为病理学的主要组成部分，因此在犬类患者群体中可以清楚地识别出来。为了我们的具体目标，我们计划使用两个纯种犬的家系和病例对照样本进行犬噪声恐惧症的遗传分析。我们将获得大约60只边境牧羊犬噪音恐惧症谱系的狗的DNA样本，以及大约50对不相关的噪音恐惧症病例和对照，分别来自边境牧羊犬和澳大利亚牧羊犬两个放牧品种。我们将使用详细的、经临床验证的行为问卷来确定噪音恐惧症的表型，然后使用全基因组SNP标记进行基因分型。将对家庭样本进行连锁分析，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更雄心勃勃的犬行为表型评估提供依据。此外，将这些发现转化为人类焦虑症的研究也将得到促进。公共卫生相关性：了解狗的噪音恐惧症，利用家狗独特的基因结构，以及它与人类行为的相似性，可能会为人类焦虑症的精神病学研究提供信息。病理行为背后的生物系统的阐明将提高我们对行为背后的分子生物学的一般理解，使狗在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.