Abstract:
Collie eye anomaly (CEA) encompasses a spectrum of different ophthalmic phenotypes from clinically inconsequential choroidal hypoplasia to blindness from coloboma of the optic nerve head (ONH). A previous study found a 7.8-kb deletion in intron 4 of the NHEJ1 gene to be associated with CEA. A genetic test based on this association is recommended for many breeds, including the Nova Scotia Duck Tolling Retriever (NSDTR). Collection of ONH coloboma-affected NSDTR showed lack of concordance of the NHEJ1 intronic deletion with ONH coloboma. Using genomewide single nucleotide polymorphism (SNP) genotyping in 7 ONH coloboma-affected NSDTR cases and 47 unaffected NSDTR controls with no ophthalmic signs, one SNP, located on chromosome 7, demonstrated genomewide significance. However, high genomic inflation may have confounded the results. Therefore, the genomewide association study was repeated using EMMAX to control for population structure in the cohort of 7 cases and 47 controls. However, no regions of the genome were significantly associated with ONH coloboma. These results failed to document significant association with the CEA locus. Due to the complex genetic etiology of ONH coloboma, the NHEJ1 intronic deletion test results should be carefully considered when making breeding decisions. If the goal is to select for visually competent dogs, our data suggest that eye examinations of puppies would be more effective as a guide in selection of breeding pairs than relying solely on currently available genetic tests.
摘要:
Collie眼异常(CEA)涵盖了一系列不同的眼科表型,从临床上无关紧要的脉络膜发育不全到视神经乳头瘤(ONH)的失明。先前的研究发现NHEJ1基因内含子4中的7.8kb缺失与CEA相关。建议对许多品种进行基于这种关联的基因测试,包括新斯科舍省鸭子收费犬(NSDTR)。受ONH结肠缺损影响的NSDTR的收集显示NHEJ1内含子缺失与ONH结肠缺损缺乏一致性。在7例受ONH结肠损伤影响的NSDTR病例和47例未受影响的NSDTR对照中使用全基因组单核苷酸多态性(SNP)基因分型,无眼科体征,一个SNP,位于7号染色体上,证明了全基因组意义。然而,高基因组膨胀可能混淆了结果。因此,在7例病例和47例对照的队列中,使用EMMAX重复进行了全基因组关联研究,以控制群体结构.然而,基因组中没有任何区域与ONH结肠缺损显著相关.这些结果未能证明与CEA基因座的显著关联。由于ONH结肠瘤的复杂遗传病因,在做出育种决定时,应仔细考虑NHEJ1内含子缺失测试结果.如果目标是选择视觉上有能力的狗,我们的数据表明,对幼犬进行眼部检查比仅仅依靠目前可用的基因测试更有效地作为选择繁殖对的指南。