Genetic Analysis of Noise Phobia

描述(由申请人提供)：这份开发性/探索性申请旨在探索噪音恐惧症的遗传基础，噪音恐惧症是家犬的一种常见行为障碍。狗是一个很好的模型系统，用来确定行为的遗传基础。犬基因组学的最新进展意味着，这些工具已经到位，可以对犬的行为特征进行严格的遗传分析。自然发生的焦虑症，与人类发现的许多类似，在狗身上很常见，而且经常在家庭中分离。焦虑症构成了犬的大部分行为病理，因此在犬患者群体中可以清楚地识别出来。为了我们的具体目标，我们计划利用两个纯品种的家系和病例对照样本进行犬类噪音恐惧症的遗传分析。我们将从波德牧羊犬噪音恐惧症家系的约60名成员中获取DNA样本，以及两个牧群品种--边境牧羊犬和澳大利亚牧羊犬中每一种的约50对无关的噪音恐惧症病例和对照。我们将使用详细和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狗的复杂行为表型，将为更雄心勃勃地评估众多品种的犬类行为表型提供理论基础。此外，还将促进将这些发现转化为人类焦虑症的研究。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之处，可能会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潜在分子生物学的总体理解，使狗能够为这一快速演变的领域做出贡献。

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.