National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA; email:
Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907, USA.
Annu Rev Anim Biosci. 2019 Feb 15;7:449-472. doi: 10.1146/annurev-animal-030117-014523. Epub 2018 Nov 12.
Dogs are second only to humans in medical surveillance and preventative health care, leading to a recent perception of increased cancer incidence. Scientific priorities in veterinary oncology have thus shifted, with a demand for cancer genetic screens, better diagnostics, and more effective therapies. Most dog breeds came into existence within the last 300 years, and many are derived from small numbers of founders. Each has undergone strong artificial selection, in which dog fanciers selected for many traits, including body size, fur type, color, skull shape, and behavior, to create novel breeds. The adoption of the breed barrier rule-no dog may become a registered member of a breed unless both its dam and its sire are registered members-ensures a relatively closed genetic pool within each breed. As a result, there is strong phenotypic homogeneity within breeds but extraordinary phenotypic variation between breeds. One consequence of this is the high level of breed-associated genetic disease. We and others have taken advantage of this to identify genes for a large number of canine maladies for which mouse models do not exist, particularly with regard to cancer.
狗在医学监测和预防保健方面仅次于人类，这导致了人们最近对癌症发病率上升的看法。因此，兽医肿瘤学的科学重点已经转移，需要进行癌症基因筛查、更好的诊断方法和更有效的治疗方法。大多数犬种在过去的 300 年内出现，其中许多是由少数祖先衍生而来。每个品种都经历了强烈的人工选择，犬爱好者选择了许多特征，包括体型、皮毛类型、颜色、头骨形状和行为，以创造新的品种。品种障碍规则的采用——除非其母犬和父犬都是注册成员，否则任何犬都不得成为一个品种的注册成员——确保了每个品种内相对封闭的遗传池。因此，品种内存在强烈的表型同质性，但品种之间存在非凡的表型变异。其结果之一是与品种相关的遗传疾病水平很高。我们和其他人已经利用这一点来识别大量犬类疾病的基因，这些疾病在老鼠模型中不存在，特别是癌症。
