Paige A Winkler, Ethan M Dawson-Baglien, Madeline C Coffey, Patrick J Venta, Kari J Ekenstedt, Simon M Petersen-Jones
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Genotyping of a SNP within the region showed 86% of OM-affected dogs were homozygous or heterozygous for the risk allele, whereas 78% of unaffected dogs were homozygous for the nonrisk allele. Sequencing of the coding regions and splice sites of four genes (c9orf72, IFNK, the 5' end of MOB3B, and the 3' end of LINGO2) and of a microRNA (MIR876) did not detect any genetic variants unique to OM-affected dogs.</p><p><strong>Conclusion: </strong>OM in Cairn Terriers maps to a 1.49 Mb region of chromosome 11. This accounts for 86% of OM cases in our DNA bank. A second locus may account for the OM phenotype in the remaining 14% of cases. Sequencing of coding regions and splice sites of positional candidate genes and a microRNA did not reveal any genetic variants unique to affected dogs. Further studies are required to elucidate the DNA variant causal for OM in Cairn Terriers and to understand the disease mechanism.</p>","PeriodicalId":23836,"journal":{"name":"Veterinary ophthalmology","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mapping the locus for ocular melanosis in Cairn Terriers.\",\"authors\":\"Paige A Winkler, Ethan M Dawson-Baglien, Madeline C Coffey, Patrick J Venta, Kari J Ekenstedt, Simon M Petersen-Jones\",\"doi\":\"10.1111/vop.13291\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To map the disease locus for familial ocular melanosis (OM) in the Cairn Terrier.</p><p><strong>Animals studied: </strong>Cairn Terriers with OM and normal control dogs.</p><p><strong>Procedure: </strong>A genome-wide association study (GWAS) was performed using 63 OM-affected and 31 control Cairn Terriers, followed by haplotype analysis. 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引用次数: 0
摘要
目的绘制凯恩梗家族性眼部黑色素沉着症(OM)的疾病基因位点图:研究动物:患有 OM 的凯恩泰瑞犬和正常对照犬:利用 63 只受 OM 影响的凯恩泰瑞犬和 31 只对照组凯恩泰瑞犬进行了全基因组关联研究(GWAS),然后进行了单体型分析。在更大的一组 OM 受影响凯恩泰瑞犬和对照组凯恩泰瑞犬中,对明显相关的单核苷酸多态性进行了基因分型。对置信区间内基因的编码区和剪接位点区进行了测序:结果:11 号染色体上 ~9.2 Mb 的区域与 OM 明显相关。单倍型分析将该区域缩小到 1.49 Mb。对该区域内一个 SNP 的基因分型显示,86% 的 OM 患病犬为风险等位基因的同源或杂合型,而 78% 的未患病犬为非风险等位基因的同源型。对四个基因(c9orf72、IFNK、MOB3B的5'端和LINGO2的3'端)的编码区和剪接位点以及一个微RNA(MIR876)进行测序后,没有发现任何OM患病犬特有的基因变异:结论:凯恩泰瑞犬的 OM 映射到 11 号染色体的 1.49 Mb 区域。在我们的 DNA 库中,86% 的 OM 病例发生在这一区域。在其余 14% 的病例中,OM 表型可能是由第二个基因位点引起的。对位置候选基因的编码区和剪接位点以及一种微RNA进行测序后,并未发现患病犬特有的基因变异。还需要进一步研究,以确定导致凯恩梗犬OM的DNA变体,并了解疾病的机理。
Mapping the locus for ocular melanosis in Cairn Terriers.
Objective: To map the disease locus for familial ocular melanosis (OM) in the Cairn Terrier.
Animals studied: Cairn Terriers with OM and normal control dogs.
Procedure: A genome-wide association study (GWAS) was performed using 63 OM-affected and 31 control Cairn Terriers, followed by haplotype analysis. A significantly associated single-nucleotide polymorphism was genotyped in a larger group of OM-affected and control Cairn Terriers. The coding and splice-site regions of genes mapping within the confidence interval were sequenced.
Results: A ~9.2 Mb region of chromosome 11 was significantly associated with OM. Haplotype analysis narrowed the region to 1.49 Mb. Genotyping of a SNP within the region showed 86% of OM-affected dogs were homozygous or heterozygous for the risk allele, whereas 78% of unaffected dogs were homozygous for the nonrisk allele. Sequencing of the coding regions and splice sites of four genes (c9orf72, IFNK, the 5' end of MOB3B, and the 3' end of LINGO2) and of a microRNA (MIR876) did not detect any genetic variants unique to OM-affected dogs.
Conclusion: OM in Cairn Terriers maps to a 1.49 Mb region of chromosome 11. This accounts for 86% of OM cases in our DNA bank. A second locus may account for the OM phenotype in the remaining 14% of cases. Sequencing of coding regions and splice sites of positional candidate genes and a microRNA did not reveal any genetic variants unique to affected dogs. Further studies are required to elucidate the DNA variant causal for OM in Cairn Terriers and to understand the disease mechanism.
期刊介绍:
Veterinary Ophthalmology is a peer-reviewed, international journal that welcomes submission of manuscripts directed towards academic researchers of veterinary ophthalmology, specialists and general practitioners with a strong ophthalmology interest. Articles include those relating to all aspects of:
Clinical and investigational veterinary and comparative ophthalmology;
Prospective and retrospective studies or reviews of naturally occurring ocular disease in veterinary species;
Experimental models of both animal and human ocular disease in veterinary species;
Anatomic studies of the animal eye;
Physiological studies of the animal eye;
Pharmacological studies of the animal eye.