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一项全基因组关联研究在犬类的12号染色体上鉴定出一个与对称性甲营养不良密切相关的区域。

A genome-wide association study identifies a region strongly associated with symmetrical onychomadesis on chromosome 12 in dogs.

作者信息

Dahlgren S, Ziener M Lund, Lingaas F

机构信息

Department of Basic Sciences and Aquatic Medicine, Norwegian University of Life Sciences, Oslo, Norway.

Fredrikstad Animal Hospital, Fredrikstad, Norway.

出版信息

Anim Genet. 2016 Dec;47(6):708-716. doi: 10.1111/age.12469. Epub 2016 Sep 14.

Abstract

Symmetrical onychomadesis causes periodic loss of claws in otherwise healthy dogs. Genome-wide association analysis in 225 Gordon Setters identified a single region associated with symmetrical onychomadesis on chromosome 12 (spanning about 3.3 mb). A meta-analysis including also English Setters indicated that this genomic region predisposes for symmetrical onychomadesis in English Setters as well. The associated region spans most of the major histocompatibility complex and nearly 1 Mb downstream. Like many other autoimmune diseases, associations of symmetrical onychomadesis with DLA class II alleles have been reported. In this study, no associated markers were revealed within any of the DLA-DRB1, -DQA1 or -DQB1 genes, and the odds for symmetrical onychomadesis in the Gordon Setters were much higher, carrying significant single nucleotide polymorphisms compared to the odds of any of the recorded DLA-DRB1/DQA1/DQB1 haplotypes. We noticed that some of the associated DLA haplotypes were different between the English Setters and the Gordon Setters. Interestingly, associated SNP chip markers showed a more consistent pattern of allelic variants related to cases or controls regardless of breed. In conclusion, the associated genetic markers identified in this study hold the potential to aid in selection of breeding animals to reduce the frequency of symmetrical onychomadesis in the dog.

摘要

对称性甲脱失会导致原本健康的犬类周期性地掉爪。对225只戈登雪达犬进行全基因组关联分析,确定了12号染色体上一个与对称性甲脱失相关的单一区域(跨度约3.3兆碱基)。一项纳入英国雪达犬的荟萃分析表明,该基因组区域也使英国雪达犬易患对称性甲脱失。相关区域涵盖了大部分主要组织相容性复合体以及下游近1兆碱基的区域。与许多其他自身免疫性疾病一样,已有报道称对称性甲脱失与犬白细胞抗原(DLA)II类等位基因有关。在本研究中,在任何DLA - DRB1、- DQA1或- DQB1基因内均未发现相关标记,并且与任何记录的DLA - DRB1 / DQA1 / DQB1单倍型的几率相比,戈登雪达犬发生对称性甲脱失的几率要高得多,携带显著的单核苷酸多态性。我们注意到英国雪达犬和戈登雪达犬之间的一些相关DLA单倍型有所不同。有趣的是,相关的单核苷酸多态性芯片标记显示,无论品种如何,与病例或对照相关的等位基因变异模式更为一致。总之,本研究中鉴定出的相关遗传标记有可能帮助选择种畜,以降低犬类对称性甲脱失的发生率。

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