Department of Veterinary Biosciences, University of Helsinki, 00014, Helsinki, Finland.
Department of Medical and Clinical Genetics, University of Helsinki, 00014, Helsinki, Finland.
Transl Psychiatry. 2020 May 28;10(1):169. doi: 10.1038/s41398-020-0849-z.
The complex phenotypic and genetic nature of anxieties hampers progress in unravelling their molecular etiologies. Dogs present extensive natural variation in fear and anxiety behaviour and could advance the understanding of the molecular background of behaviour due to their unique breeding history and genetic architecture. As dogs live as part of human families under constant care and monitoring, information from their behaviour and experiences are easily available. Here we have studied the genetic background of fearfulness in the Great Dane breed. Dogs were scored and categorised into cases and controls based on the results of the validated owner-completed behavioural survey. A genome-wide association study in a cohort of 124 dogs with and without socialisation as a covariate revealed a genome-wide significant locus on chromosome 11. Whole exome sequencing and whole genome sequencing revealed extensive regions of opposite homozygosity in the same locus on chromosome 11 between the cases and controls with interesting neuronal candidate genes such as MAPK9/JNK2, a known hippocampal regulator of anxiety. Further characterisation of the identified locus will pave the way for molecular understanding of fear in dogs and may provide a natural animal model for human anxieties.
焦虑的复杂表型和遗传特性阻碍了对其分子病因的研究进展。狗在恐惧和焦虑行为方面表现出广泛的自然变异，并且由于其独特的繁殖历史和遗传结构，可能会促进对行为分子背景的理解。由于狗作为人类家庭的一部分生活，受到持续的照顾和监测，因此它们的行为和经历信息很容易获得。在这里，我们研究了大丹犬品种的恐惧的遗传背景。根据经过验证的主人完成的行为调查的结果，对狗进行评分并将其分为病例和对照。在一项包含 124 只具有和不具有社交化作为协变量的狗的队列中进行的全基因组关联研究显示，在 11 号染色体上存在一个与全基因组显著相关的位点。外显子组测序和全基因组测序揭示了病例和对照之间 11 号染色体上同一位点的广泛的相反纯合区域，其中有 MAPK9/JNK2 等有趣的神经元候选基因，该基因是已知的焦虑的海马调节因子。对鉴定出的位点的进一步表征将为狗的恐惧的分子理解铺平道路，并可能为人类焦虑症提供天然的动物模型。
