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犬髋关节发育不良的遗传预测模型:全基因组关联研究(GWAS)与候选基因方法的整合。

A genetic predictive model for canine hip dysplasia: integration of Genome Wide Association Study (GWAS) and candidate gene approaches.

作者信息

Bartolomé Nerea, Segarra Sergi, Artieda Marta, Francino Olga, Sánchez Elisenda, Szczypiorska Magdalena, Casellas Joaquim, Tejedor Diego, Cerdeira Joaquín, Martínez Antonio, Velasco Alfonso, Sánchez Armand

机构信息

Progenika Biopharma SA, a Grifols Company, Derio, Bizkaia, Spain.

Bioibérica SA, Barcelona, Spain.

出版信息

PLoS One. 2015 Apr 13;10(4):e0122558. doi: 10.1371/journal.pone.0122558. eCollection 2015.

Abstract

Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B) and case (D/E). C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85) and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors' opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds.

摘要

犬髋关节发育不良是全球犬类中最普遍的发育性骨科疾病之一。不幸的是,基于X光诊断的根除该疾病计划的成功率很低。在当前基于表型的方法中增加诊断性基因工具的使用可能会有所帮助。本研究的目的是开发一种用于早期诊断拉布拉多猎犬髋关节发育不良的基因预后测试。为了开发我们的DNA测试,招募了775只拉布拉多猎犬。为每只狗采集一份血样和一张腹背位髋关节X光片。根据它们的FCI髋关节评分将狗分为两组:对照组(A/B)和病例组(D/E)。C级狗未纳入样本。结合全基因组关联研究(GWAS)和使用单核苷酸多态性(SNP)的候选基因策略进行基因特征分析,进行了病例对照群体关联研究。使用逻辑回归开发了一个包含7个SNP的数学模型。该模型显示出良好的准确性(ROC曲线下面积 = 0.85),并在114只狗的独立群体中得到验证。一旦知道髋关节发育不良的遗传易感性,这种预后基因测试就是选择最合适治疗方法的有用工具。因此,它允许对该疾病进行更个性化的管理。它也适用于基因选择过程,因为育种者一旦能够采集血样,就可以从该测试提供的信息中受益,并据此采取行动。作者认为,向基因组筛查的转变可能会在未来对减少犬髋关节发育不良做出重要贡献。总之,基于患有髋关节发育不良的拉布拉多猎犬的基因和X光信息,我们开发了一种用于早期诊断拉布拉多猎犬髋关节发育不良的准确预测性基因测试。然而,有必要进行进一步的研究,以评估这种基因测试在其他犬种中的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d266/4395148/389ca4702dc3/pone.0122558.g001.jpg

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