PDF(Pubmed)
Abstract：
Multiocular defect has been described in different canine breeds, including the Old English Sheepdog. Affected dogs typically present with multiple and various ocular abnormalities. We carried out whole genome sequencing on an Old English Sheepdog that had been diagnosed with hereditary cataracts at the age of five and then referred to a board-certified veterinary ophthalmologist due to owner-reported visual deterioration. An ophthalmic assessment revealed that there was bilateral vitreal degeneration, macrophthalmos, and spherophakia in addition to cataracts. Follow-up consultations revealed cataract progression, retinal detachment, uveitis and secondary glaucoma. Whole genome sequence filtered variants private to the case, shared with another Old English Sheepdog genome and predicted to be deleterious were genotyped in an initial cohort of six Old English Sheepdogs (three affected by multiocular defect and three control dogs without evidence of inherited eye disease). Only one of the twenty-two variants segregated correctly with multiocular defect. The variant is a single nucleotide substitution, located in the collagen-type gene COL11A1, c.1775T>C, that causes an amino acid change, p.Phe1592Ser. Genotyping of an additional 14 Old English Sheepdogs affected by multiocular defect revealed a dominant mode of inheritance with four cases heterozygous for the variant. Further genotyping of hereditary cataract-affected Old English Sheepdogs revealed segregation of the variant in eight out of nine dogs. In humans, variants in the COL11A1 gene are associated with Stickler syndrome type II, also dominantly inherited.
摘要：
多眼缺陷已在不同犬种中被描述，包括古老的英国牧羊犬。受影响的狗通常存在多个和各种眼部异常。我们对一只在5岁时被诊断出患有遗传性白内障的老英国牧羊犬进行了全基因组测序，然后由于主人报告的视力恶化而被转介给董事会认证的兽医眼科医生。眼科评估显示有双侧玻璃体变性，大眼眼，除了白内障外，还有球形无眼。随访咨询显示白内障进展，视网膜脱离,葡萄膜炎和继发性青光眼。全基因组序列过滤的变异对案件来说是私人的，与另一个古老的英国牧羊犬基因组共享并预测有害，在最初的六只古老的英国牧羊犬（三只受多眼缺陷影响，三只对照犬没有遗传性眼病的证据）队列中进行了基因分型。22种变体中只有一种与多眼缺陷正确分离。该变体是单核苷酸取代，位于胶原型基因COL11A1，c.1775T>C，导致氨基酸变化，p.Phe1592Ser.对另外14只受多眼缺陷影响的古英国牧羊犬进行基因分型，揭示了一种显性遗传方式，其中4例变种为杂合。对遗传性白内障影响的旧英国牧羊犬的进一步基因分型显示，在九只狗中的八只中，该变体被隔离。在人类中,COL11A1基因的变异与II型Stickler综合征相关，也主要继承。
