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全基因组关联研究在达克斯猎犬中:鉴定影响椎间盘钙化的主要位点。

Genome-wide association study in Dachshund: identification of a major locus affecting intervertebral disc calcification.

机构信息

Department of Basic Animal and Veterinary Sciences, Faculty of Life Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870 Frederiksberg C, Denmark.

出版信息

J Hered. 2011 Sep-Oct;102 Suppl 1:S81-6. doi: 10.1093/jhered/esr021.

Abstract

Intervertebral disc calcification and herniation commonly affects Dachshund where the predisposition is caused by an early onset degenerative process resulting in disc calcification. A continuous spectrum of disc degeneration is seen within and among dog breeds, suggesting a multifactorial etiology. The number of calcified discs at 2 years of age determined by a radiographic evaluation is a good indicator of the severity of disc degeneration and thus serves as a measure for the risk of developing intervertebral disc herniation. The aim of the study was to identify genetic variants associated with intervertebral disc calcification in Dachshund through a genome-wide association (GWA) study. Based on thorough radiographic examinations, 48 cases with ≥ 6 disc calcifications or surgically treated for disc herniation and 46 controls with 0-1 disc calcifications were identified. GWA using the Illumina CanineHD BeadChip identified a locus on chromosome 12 from 36.8 to 38.6 Mb with 36 markers reaching genome-wide significance (P(genome) = 0.00001-0.026). This study suggests that a major locus on chromosome 12 harbors genetic variations affecting the development of intervertebral disc calcification in Dachshund.

摘要

椎间盘钙化和突出症通常会影响达克斯猎犬,其易感性是由早期退行性病变引起的椎间盘钙化所致。在犬种之间和内部可以看到椎间盘退变的连续谱,这表明存在多因素病因。通过放射学评估在 2 岁时确定的钙化椎间盘数量是椎间盘退变严重程度的良好指标,因此可作为发生椎间盘突出症风险的衡量标准。本研究旨在通过全基因组关联 (GWA) 研究鉴定达克斯猎犬椎间盘钙化相关的遗传变异。基于彻底的放射学检查,鉴定出 48 例具有≥6 个椎间盘钙化或接受椎间盘突出症手术治疗的病例和 46 例具有 0-1 个椎间盘钙化的对照。使用 Illumina CanineHD BeadChip 的全基因组关联分析鉴定出染色体 12 上的一个位点,位于 36.8 至 38.6 Mb 之间,有 36 个标记达到全基因组显著水平 (P(genome) = 0.00001-0.026)。本研究表明,染色体 12 上的一个主要位点携带有影响达克斯猎犬椎间盘钙化发展的遗传变异。

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