Bauer A, Hadji Rasouliha S, Brunner M T, Jagannathan V, Bucher I, Bannoehr J, Varjonen K, Bond R, Bergvall K, Welle M M, Roosje P, Leeb T
Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, 3001, Switzerland.
Dermfocus, Vetsuisse Faculty, University of Bern, Bern, 3001, Switzerland.
Anim Genet. 2019 Feb;50(1):97-100. doi: 10.1111/age.12743. Epub 2018 Nov 15.
Major characteristics of coat variation in dogs can be explained by variants in only a few genes. Until now, only one missense variant in the KRT71 gene, p.Arg151Trp, has been reported to cause curly hair in dogs. However, this variant does not explain the curly coat in all breeds as the mutant Trp allele, for example, is absent in Curly Coated Retrievers. We sequenced the genome of a Curly Coated Retriever at 22× coverage and searched for variants in the KRT71 gene. Only one protein-changing variant was present in a homozygous state in the Curly Coated Retriever and absent or present in a heterozygous state in 221 control dogs from different dog breeds. This variant, NM_001197029.1:c.1266_1273delinsACA, was an indel variant in exon 7 that caused a frameshift and an altered and probably extended C-terminus of the KRT71 protein NP_001183958.1:p.(Ser422ArgfsTer?). Using Sanger sequencing, we found that the variant was fixed in a cohort of 125 Curly Coated Retrievers and segregating in five of 14 additionally tested breeds with a curly or wavy coat. KRT71 variants cause curly hair in humans, mice, rats, cats and dogs. Specific KRT71 variants were further shown to cause alopecia. Based on this knowledge from other species and the predicted molecular consequence of the newly identified canine KRT71 variant, it is a compelling candidate causing a second curly hair allele in dogs. It might cause a slightly different coat phenotype than the previously published p.Arg151Trp variant and could potentially be associated with follicular dysplasia in dogs.
犬类被毛变异的主要特征仅由少数几个基因的变异就能解释。到目前为止，据报道KRT71基因中只有一个错义变异p.Arg151Trp会导致犬类出现卷毛。然而，这个变异并不能解释所有品种的卷毛情况，例如卷毛寻回犬中就不存在突变的色氨酸（Trp）等位基因。我们对一只卷毛寻回犬的基因组进行了22倍覆盖度的测序，并在KRT71基因中寻找变异。在这只卷毛寻回犬中，只有一个导致蛋白质改变的变异以纯合状态存在，而在来自不同犬种的221只对照犬中，该变异不存在或呈杂合状态。这个变异，NM_001197029.1:c.1266_1273delinsACA，是外显子7中的一个插入缺失变异，它导致了移码，并使KRT71蛋白NP_001183958.1:p.(Ser422ArgfsTer?)的C末端发生改变且可能延长。通过桑格测序，我们发现该变异在125只卷毛寻回犬群体中是固定的，并且在另外14个经测试的有卷毛或波浪毛的品种中有5个品种存在该变异的分离现象。KRT71变异在人类、小鼠、大鼠、猫和犬类中都会导致卷毛。进一步研究表明，特定的KRT71变异会导致脱发。基于其他物种的这些知识以及新发现的犬类KRT71变异的预测分子后果，它是导致犬类出现第二个卷毛等位基因的有力候选基因。它可能会导致与之前报道的p.Arg151Trp变异略有不同的被毛表型，并且可能与犬类的毛囊发育异常有关。
