Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies.
Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies.
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DOI：
10.1007/s00335-011-9361-3
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发表时间：
2012-02
期刊：
影响因子：
2.5
通讯作者：
Aguirre, Gustavo D.
中科院分区：
文献类型：
--
作者：
Miyadera, Keiko;Acland, Gregory M.;Aguirre, Gustavo D.
已知人类和狗的视网膜致盲疾病存在相当大的临床和分子变异。不同形式的视网膜疾病发生在特定品种中，由每个隔离繁殖群体内的突变分离引起。虽然寻找犬视网膜疾病相关基因和突变的分子研究在很大程度上受益于品种内的表型和遗传一致性，但品种内和品种间的变异通常在阐明分子基础方面发挥着关键作用。对犬视网膜变性的表型、等位基因和遗传异质性的认识越来越多，表明整体情况比最初想象的要复杂得多。在过去的20年里，已经开发和测试了各种方法来寻找狗的遗传特征的基因和突变，这取决于遗传工具和样本资源的可用性。候选基因、连锁分析和全基因组关联研究迄今已在至少58个犬种中确定了18个视网膜疾病相关基因中的24个突变。这些基因中的许多与人类视网膜疾病有关，从而提供了研究发病机制和正常视力中作用的机会。在治疗干预，如基因治疗的应用已被证明是成功的，最初在自然发生的狗模型，然后在人类患者的试验。其他基因的人类同源物没有与视网膜疾病相关的潜在候选人，以解释等价的人类疾病，并有助于理解他们的视觉功能。
Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision.
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影响因子：
3.4
作者：
AGUIRRE, GD;ACLAND, GM
通讯作者：
ACLAND, GM
影响因子：
3.7
作者：
Bannasch D;Young A;Myers J;Truvé K;Dickinson P;Gregg J;Davis R;Bongcam-Rudloff E;Webster MT;Lindblad-Toh K;Pedersen N
通讯作者：
Pedersen N
影响因子：
56.9
作者：
ABRAMOV, I;GORDON, J;LABOSSIERE, E
通讯作者：
LABOSSIERE, E
影响因子：
4.4
作者：
Acland, GM;Ray, K;Aguirre, GD
通讯作者：
Aguirre, GD
DOI：
10.1073/pnas.0812297106
发表时间：
2009-02-24
影响因子：
11.1
作者：
Awano, Tomoyuki;Johnson, Gary S.;Coates, Joan R.
通讯作者：
Coates, Joan R.