Department of Population Health and Reproduction, University of California, Davis, Davis, CA 95616, USA.
Department of Pathology, Microbiology, & Immunology, University of California, Davis, Davis, CA 95616, USA.
G3 (Bethesda). 2022 Nov 4;12(11). doi: 10.1093/g3journal/jkac227.
Pigment production and distribution is controlled through multiple genes, resulting in a wide range of coat color phenotypes in dogs. Dogs that produce only the pheomelanin pigment vary in intensity from white to deep red. The Poodle breed has a wide range of officially recognized coat colors, including the pheomelanin-based white, cream, apricot, and red coat colors, which are not fully explained by the previously identified genetic variants involved in pigment intensity. Here, a genome-wide association study for pheomelanin intensity was performed in Poodles which identified an association on canine chromosome 18. Whole-genome sequencing data revealed an SNN retrocopy insertion (SNNL1) in apricot and red Poodles within the associated region on chromosome 18. While equal numbers of melanocytes were observed in all Poodle skin hair bulbs, higher melanin content was observed in the darker Poodles. Several genes involved in melanogenesis were also identified as highly overexpressed in red Poodle skin. The most differentially expressed gene however was GPR22, which was highly expressed in red Poodle skin while unexpressed in white Poodle skin (log2 fold change in expression 6.1, P < 0.001). GPR22 is an orphan G-protein-coupled receptor normally expressed exclusively in the brain and heart. The SNNL1 retrocopy inserted 2.8 kb upstream of GPR22 and is likely disrupting regulation of the gene, resulting in atypical expression in the skin. Thus, we identify the SNNL1 insertion as a candidate variant for the CFA18 pheomelanin intensity locus in red Poodles.
色素的产生和分布受多个基因控制，导致狗的毛色表型多种多样。只产生真黑色素的狗，从白色到深红色，颜色强度各不相同。贵宾犬有多种官方认可的毛色，包括基于真黑色素的白色、奶油色、杏色和红色，这些毛色不能完全用先前确定的与色素强度相关的遗传变异来解释。在这里，对贵宾犬的真黑色素强度进行了全基因组关联研究，在犬 18 号染色体上发现了一个与真黑色素强度相关的关联。全基因组测序数据显示，在 18 号染色体相关区域的杏色和红色贵宾犬中存在一个 SNN 反转录插入（SNNL1）。虽然在所有贵宾犬的皮肤毛囊中观察到的黑素细胞数量相同，但在颜色较深的贵宾犬中观察到的黑色素含量更高。还鉴定出一些参与黑色素生成的基因在红色贵宾犬皮肤中高度过表达。然而，差异表达最明显的基因是 GPR22，它在红色贵宾犬皮肤中高度表达，而在白色贵宾犬皮肤中不表达（表达的对数倍数变化为 6.1，P < 0.001）。GPR22 是一种孤儿 G 蛋白偶联受体，通常仅在大脑和心脏中表达。SNNL1 反转录插入 GPR22 的上游 2.8 kb 处，可能破坏了该基因的调控，导致其在皮肤中出现异常表达。因此，我们将 SNNL1 插入鉴定为红色贵宾犬 CFA18 真黑色素强度基因座的候选变异。
