Todhunter Rory J, Casella George, Bliss Stuart P, Lust George, Williams Alma Jo, Hamilton Samuel, Dykes Nathan L, Yeager Amy E, Gilbert Robert O, Burton-Wurster Nancy I, Mellersh Cathryn C, Acland Gregory M
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Am J Vet Res. 2003 Apr;64(4):418-24. doi: 10.2460/ajvr.2003.64.418.
To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree.
147 Labrador Retrievers, Greyhounds, and their crossbreed offspring.
Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined.
For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7 CONCLUSIONS AND CLINICAL SIGNIFICANCE: Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs.
估算从一个实验性家系中找出与犬髋关节发育不良遗传性状相关联所需的犬只数量。
147只拉布拉多寻回犬、灵缇犬及其杂交后代。
将患有髋关节发育不良的拉布拉多寻回犬与未受影响的灵缇犬进行杂交。记录股骨头骨化检测时的年龄、牵张指数(DI)、髋关节背外侧半脱位(DLS)评分以及髋关节骨关节炎(OA)情况。确定单个标记与控制回交犬发育异常性状100%变异的数量性状位点(QTL)连锁的效能。
对于观察到的效应大小、重组率为0.05以及杂合度为0.75时的DI,F1与灵缇犬回交一代中的35只犬将产生效能为0.8的连锁。对于DLS评分,回交至拉布拉多寻回犬一代中的35只犬在相同效能下可产生连锁。对于骨化情况,回交至原始拉布拉多寻回犬的45只犬在相同效能下可产生连锁。预计找出与髋关节OA连锁所需的犬只数量较少。同时在4个位点检测与DLS的连锁,每个位点控制25%的表型变异,总体效能为0.7。结论及临床意义:基于这种保守的单标记估计,通过培育合理数量的回交犬,该家系有足够的效能找出与髋关节发育不良和髋关节OA易感位点相关的微卫星。