Kerns Julie A, Newton J, Berryere Tom G, Rubin Edward M, Cheng Jan-Fang, Schmutz Sheila M, Barsh Gregory S
Departments of Genetics and Pediatrics, Stanford University, Stanford, California 94305, USA.
Mamm Genome. 2004 Oct;15(10):798-808. doi: 10.1007/s00335-004-2377-1.
The interaction between two genes, Agouti and Melanocortin-1 receptor ( Mc1r), produces diverse pigment patterns in mammals by regulating the type, amount, and distribution pattern of the two pigment types found in mammalian hair: eumelanin (brown/black) and pheomelanin (yellow/red). In domestic dogs ( Canis familiaris), there is a tremendous variation in coat color patterns between and within breeds; however, previous studies suggest that the molecular genetics of pigment-type switching in dogs may differ from that of other mammals. Here we report the identification and characterization of the Agouti gene from domestic dogs, predicted to encode a 131-amino-acid secreted protein 98% identical to the fox homolog, and which maps to chromosome CFA24 in a region of conserved linkage. Comparative analysis of the Doberman Pinscher Agouti cDNA, the fox cDNA, and 180 kb of Doberman Pinscher genomic DNA suggests that, as with laboratory mice, different pigment-type-switching patterns in the canine family are controlled by alternative usage of different promoters and untranslated first exons. A small survey of Labrador Retrievers, Greyhounds, Australian Shepherds, and German Shepherd Dogs did not uncover any polymorphisms, but we identified a single nucleotide variant in black German Shepherd Dogs predicted to cause an Arg-to-Cys substitution at codon 96, which is likely to account for recessive inheritance of a uniform black coat.
两个基因，刺鼠信号蛋白（Agouti）基因和黑皮质素-1受体（Mc1r）基因之间的相互作用，通过调节哺乳动物毛发中发现的两种色素类型，即真黑素（棕色/黑色）和褐黑素（黄色/红色）的类型、数量和分布模式，在哺乳动物中产生了多样的色素模式。在家犬（犬属家犬）中，不同品种之间以及同一品种内部的毛色模式存在巨大差异；然而，先前的研究表明，犬类色素类型转换的分子遗传学可能与其他哺乳动物不同。在此，我们报告了家犬Agouti基因的鉴定和特征，该基因预计编码一种131个氨基酸的分泌蛋白，与狐狸的同源蛋白有98%的同一性，并且定位于保守连锁区域的犬染色体CFA24上。对杜宾犬Agouti cDNA、狐狸cDNA以及180 kb杜宾犬基因组DNA的比较分析表明，与实验小鼠一样，犬科动物中不同的色素类型转换模式是由不同启动子和非翻译第一外显子的交替使用所控制的。对拉布拉多寻回犬、灵缇犬、澳大利亚牧羊犬和德国牧羊犬的一项小型调查未发现任何多态性，但我们在黑色德国牧羊犬中鉴定出一个单核苷酸变体，预计该变体将导致第96位密码子处的精氨酸被半胱氨酸取代，这可能是纯色黑色被毛隐性遗传的原因。
