Todhunter R J, Acland G M, Olivier M, Williams A J, Vernier-Singer M, Burton-Wurster N, Farese J P, Gröhn Y T, Gilbert R O, Dykes N L, Lust G
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
J Hered. 1999 Jan-Feb;90(1):83-92. doi: 10.1093/jhered/90.1.83.
Canine hip dysplasia (CHD) is a prevalent, debilitating, polygenic disease characterized by hip subluxation and laxity which results in osteoarthritis. We are developing an informative pedigree for linkage analysis of CHD. The seven greyhound founders had excellent hip conformation with high dorsolateral subluxation scores (percentage of femoral head covered by the dorsal acetabulum in a weight-bearing position) of 66 +/- 4% (mean +/- SD averaged over both hips) and low hip distraction (laxity) indices of 0.14 +/- 0.08. Nine greyhounds bred on site had radiographic evidence of ossification in the capital femoral chondroepiphysis at 7.7 +/- 0.9 days of age. At 8 months of age they had a mean distraction index of 0.24 +/- 0.08 and dorsolateral subluxation score of 76 +/- 1%. Of the four dysplastic Labrador retriever founders, three had mean age at onset of capital femoral chondroeplphyseal ossification of 20 +/- 7 days of age n = 3) and a mean distraction index of 0.46 +/- 0.1 accompanied by hip osteoarthritis. Thirty-four F1s had mean onset of capital femoral ossification (10.7 +/- 4.0 days of age) and mean dorsolateral subluxation scores (61 +/- 12%) similar to the greyhound founders, but distraction indices (0.42 +/- 0.2) more similar to the Labrador retriever founders. One F1 had CHD radiographically but none of 20 F1s had osteoarthritis at necropsy at 10 months of age. These data suggested that maximum passive laxity (as measured by the distraction index) and normal osseous conformation (as indicated by a high dorsolateral subluxation score) were both dominant traits and were controlled by separate quantitative trait loci (QTL). Forty-three back-crosses between F1s with the highest hip laxity and greyhound founders had mean onset of capital femoral ossification at 9.9 +/- 2.6 days of age. Of 10 dogs in the backcross generation that have reached 8 months of age, 2 had palpable subluxation without marked CHD radiographically. The mean distraction index of these dogs was 0.36 +/- 0.16 and the dorsolateral subluxation score was 65 +/- 5%. Although dogs in the backcross generation that were three-quarter greyhound had a broad range of hip laxity, a protective effect of the greyhound QTLs for good osseous conformation has mitigated thus far against subluxation and CHD.
犬髋关节发育不良（CHD）是一种常见的、使人衰弱的多基因疾病，其特征为髋关节半脱位和松弛，进而导致骨关节炎。我们正在构建一个信息丰富的家系用于CHD的连锁分析。七只灵缇犬祖先具有优良的髋关节形态，背外侧半脱位评分（负重位时股骨头被髋臼背侧覆盖的百分比）较高，平均为66±4%（双侧髋关节的平均值±标准差），髋关节松弛指数较低，为0.14±0.08。在现场繁育的九只灵缇犬在7.7±0.9日龄时，股骨头软骨骨骺有骨化的影像学证据。在8月龄时，它们的平均松弛指数为0.24±0.08，背外侧半脱位评分为76±1%。在四只患有发育异常的拉布拉多寻回犬祖先中，三只股骨头软骨骨骺骨化开始的平均年龄为20±7日龄（n = 3），平均松弛指数为0.46±0.1，并伴有髋关节骨关节炎。34只F1代犬股骨头骨化开始的平均年龄（10.7±4.0日龄）和背外侧半脱位评分（61±12%）与灵缇犬祖先相似，但松弛指数（0.42±0.2）更接近拉布拉多寻回犬祖先。一只F1代犬经影像学检查患有CHD，但在10月龄尸检时，20只F1代犬中没有一只患有骨关节炎。这些数据表明，最大被动松弛度（通过松弛指数测量）和正常的骨形态（通过较高的背外侧半脱位评分表示）都是显性性状，且由不同的数量性状位点（QTL）控制。髋关节松弛度最高的F1代犬与灵缇犬祖先进行了43次回交，股骨头骨化开始的平均年龄为9.9±2.6日龄。在回交一代中已达8月龄的10只犬中，2只可触及半脱位，但影像学上无明显的CHD表现。这些犬的平均松弛指数为0.36±0.16，背外侧半脱位评分为65±5%。尽管回交一代中具有四分之三灵缇犬血统的犬髋关节松弛度范围较广，但到目前为止，灵缇犬QTLs对良好骨形态的保护作用减轻了半脱位和CHD的发生。
