Zhang Q, Baldwin V J, Acland G M, Parshall C J, Haskel J, Aguirre G D, Ray K
James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
J Hered. 1999 Jan-Feb;90(1):57-61. doi: 10.1093/jhered/90.1.57.
Photoreceptor dysplasia (pd) is one of a group of at least six distinct autosomal and one X-linked retinal disorders identified in dogs which are collectively known as progressive retinal atrophy (PRA). It is an early onset retinal disease identified in miniature schnauzer dogs, and pedigree analysis and breeding studies have established autosomal recessive inheritance of the disease. Using a gene-based approach, a number of retina-expressed genes, including some members of the phototransduction pathway, have been causally implicated in retinal diseases of humans and other animals. Here we examined seven such potential candidate genes (opsin, RDS/peripherin, ROM1, rod cGMP-gated cation channel alpha-subunit, and three subunits of transducin) for their causal association with the pd locus by testing segregation of intragenic markers with the disease locus, or, in the absence of informative polymorphisms, sequencing of the coding regions of the genes. Based on these results, we have conclusively excluded four photoreceptor-specific genes as candidates for pd by linkage analysis. For three other photoreceptor-specific genes, we did not find any mutation in the coding sequences of the genes and have excluded them provisionally. Formal exclusion would require investigation of the levels of expression of the candidate genes in pd-affected dogs relative to age-matched controls. At present we are building suitable informative pedigrees for the disease locus with a sufficient number of meiosis to be useful for genomewide screening. This should identify markers linked to the disease locus and eventually permit progress toward the identification of the photoreceptor dysplasia gene and the disease-causing mutation.
光感受器发育异常（pd）是在犬类中发现的一组至少六种不同的常染色体和一种X连锁视网膜疾病之一，这些疾病统称为进行性视网膜萎缩（PRA）。它是在迷你雪纳瑞犬中发现的一种早发性视网膜疾病，系谱分析和育种研究已确定该疾病为常染色体隐性遗传。使用基于基因的方法，许多视网膜表达基因，包括光转导途径的一些成员，已被证明与人类和其他动物的视网膜疾病存在因果关系。在这里，我们通过测试基因内标记与疾病位点的分离情况，或者在缺乏信息多态性的情况下，对基因编码区进行测序，来研究七个这样的潜在候选基因（视蛋白、RDS/外周蛋白、ROM1、杆状细胞cGMP门控阳离子通道α亚基和转导素的三个亚基）与pd位点的因果关系。基于这些结果，我们通过连锁分析最终排除了四个光感受器特异性基因作为pd的候选基因。对于其他三个光感受器特异性基因，我们在基因编码序列中未发现任何突变，并暂时排除了它们。正式排除需要研究候选基因在受pd影响的犬类相对于年龄匹配对照中的表达水平。目前，我们正在为疾病位点构建合适的信息丰富的系谱，其减数分裂数量足以用于全基因组筛选。这应该能够识别与疾病位点连锁的标记，并最终有助于识别光感受器发育异常基因和致病突变。
