Heritability and segregation analysis of osteosarcorna in the Scottish deerhound
Heritability and segregation analysis of osteosarcorna in the Scottish deerhound
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DOI：
10.1016/j.ygeno.2007.05.001
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发表时间：
2007-09-01
期刊：
影响因子：
4.4
通讯作者：
Dillberger, John
中科院分区：
文献类型：
--
作者：
Phillips, Jeffrey C.;Stephenson, Betty;Dillberger, John
骨肉瘤是狗最常见的恶性骨肿瘤，和它的人类同源物一样，具有侵略性的局部行为和高转移率的特点。苏格兰猎鹿犬是一种有15%骨肉瘤发病率的狗，代表了一种优秀的自然发生的人类疾病的大型动物模型。作为前瞻性健康研究的一部分，我们模拟了骨肉瘤表型在1000多只相关猎鹿的种群中的传播。分别用方差分析、分离分析和线性模型估计遗传力、推测传递模型和确定该表型在品种内的协变量效应。经方差成分分析，遗传力(H2)为0.69。对6种遗传模型进行了分离分析，根据Akaike的信息准则，最简约的模型是显性表达的孟德尔主基因模型。线性模型确定性别和基因是疾病结局的重要预测因子。重要的是，性激素暴露的持续时间、体重和成熟时的身高并不是预后的重要预测因素。因此，假定的高危等位基因的遗传与疾病发生的风险>；75%相关
Osteosarcoma is the most common malignant bone tumor in dogs and, like its human orthologue, is characterized by aggressive local behavior and high metastatic rates. The Scottish deerhound is a breed of dog with a > 15% incidence of osteosarcoma and represents an excellent spontaneously occurring large-animal model of the human disease. We modeled the transmission of the osteosarcoma phenotype in a population of over 1000 related deerhounds ascertained as part of a prospective health study. Variance component analysis, segregation analysis, and linear modeling were performed to evaluate heritability, to infer the presumptive transmission model, and to identify covariate effects for this phenotype within the breed, respectively. Based on variance component analysis, heritability (h 2) was estimated to be 0.69. Six transmission models were analyzed by segregation analysis; based on Akaike's information criteria, the most parsimonious model was the Mendelian major gene model with dominant expression. Linear modeling identified gender and genotype as significant predictors of disease outcome. Importantly, duration of gonadal hormone exposure, weight, and height at maturity were not significant predictors of outcome. Inheritance of the putative high-risk allele was thus associated with >75% risk of disease occurrence compared to the