Canine brachycephaly is associated with a retrotransposon-mediated missplicing of SMOC2

In morphological terms, “form” is used to describe an object’s shape and size. In dogs, facial form is stunningly diverse. Facial retrusion, the proximodistal shortening of the snout and widening of the hard palate is common to brachycephalic dogs and is a welfare concern, as the incidence of respiratory distress and ocular trauma observed in this class of dogs is highly correlated with their skull form. Progress to identify the molecular underpinnings of facial retrusion is limited to association of a missense mutation in BMP3 among small brachycephalic dogs. Here, we used morphometrics of skull isosurfaces derived from 374 pedigree and mixed-breed dogs to dissect the genetics of skull form. Through deconvolution of facial forms, we identified quantitative trait loci that are responsible for canine facial shapes and sizes. Our novel insights include recognition that the FGF4 retrogene insertion, previously associated with appendicular chondrodysplasia, also reduces neurocranium size. F...

在形态学领域中，“形态”用于描述物体的外形与尺寸。犬类的面部形态呈现出惊人的多样性。面部后移（facial retrusion）——即口鼻部近远端缩短与硬腭宽度增加——是短头颅犬（brachycephalic dogs）的常见特征，同时也是一项动物福利隐患：该类犬只出现呼吸窘迫与眼部创伤的概率与其颅骨形态高度相关。目前针对面部后移的分子机制研究进展有限，仅在小型短头颅犬中发现其与BMP3（骨形态发生蛋白3，bone morphogenetic protein 3）基因的错义突变存在关联。本研究通过对374只纯种犬与混血犬的颅骨等值面进行形态测量学（morphometrics）分析，以此解析颅骨形态的遗传基础。通过对面部形态进行反卷积分解，本研究鉴定出调控犬类面部外形与尺寸的数量性状位点（quantitative trait loci）。本研究的新发现包括：此前被证实与肢体软骨发育不良相关的FGF4（成纤维细胞生长因子4，fibroblast growth factor 4）逆转录基因插入突变，同样会缩小神经颅的尺寸。F...