Genetic interactions in the pigmentation pathway in dogs

我们研究计划的重点是了解在狗身上产生色素沉着模式所涉及的突变。这是一个很好的遗传学教学工具，因为狗的特征是显而易见的，而且狗是一种学生很容易联想到的动物。色素沉着是一种复杂的特征，它允许我们探索许多遗传原理，远远超出了经典的孟德尔遗传。在过去的几年里，我们研究了几个基因，现在已经到了可以更好地梳理这些基因之间的基因相互作用的阶段，并试图确定突变如何相互作用，以产生只有当多个基因发生突变时才会发生的新模式。最近的一个例子是Salukis中的Grizz型和阿富汗猎犬中的多米诺骨牌模式，其中两个基因必须有突变，一个在启动子(ASIP)，一个在编码序列(MC1R)。我们现在也能够更好地阐明与色素沉着有关的上位性相互作用。表型复制的概念在经典文献中已经讨论过了，但我们现在发现了两种不同的遗传机制如何导致相同表型的例子(即ASIP中的隐性遗传突变和DEFB103中的显性遗传突变都可以产生黑色)。我们的下一个目标是研究“修饰”基因。遗传学的经典文献表明，这些基因会相互作用，产生表型上的细微差异。

The focus of our research program is to understand the mutations involved in producing pigmentation patterns in dogs. This is an excellent teaching tool in genetics because the traits are visible and the dog is an animal that students easily relate to. Pigmentation is a complex trait that allows us to explore many principles of inheritance, well beyond classical Mendelian inheritance. We have studied several genes in the past few years and have now reached the stage where we can better tease apart gene interactions among these genes and try to determine how mutations can interact to produce new patterns that occur only if more than one gene has a mutation. A recent example of this is the pattern called grizzle in Salukis and domino in Afghan Hounds in which two genes must have a mutation, one in the promoter (ASIP) and one in the coding sequence (MC1R). We are also now able to better elucidate epistatic interactions involved in pigmentation. The concept of phenocopy has been discussed in classical literature but we have now discovered examples of how two distinct genetic mechanisms can lead to the same phenotype (i.e. a recessively inherited mutation in ASIP and a dominantly inherited mutation in DEFB103 can both produce black coat color). Our next objective is to study "modifier" genes. The classical literature in genetics has suggested that such genes will interact to produce subtle differences in phenotype.