A canine BCAN microdeletion associated with episodic falling syndrome.
A canine BCAN microdeletion associated with episodic falling syndrome.
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DOI：
10.1016/j.nbd.2011.07.014
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发表时间：
2012-01
影响因子：
6.1
通讯作者：
Harvey, Robert J.
中科院分区：
文献类型：
--
作者：
Gill, Jennifer L.;Tsai, Kate L.;Krey, Christa;Noorai, Rooksana E.;Vanbellinghen, Jean-Francois;Garosi, Laurent S.;Shelton, G. Diane;Clark, Leigh Anne;Harvey, Robert J.
阵发性跌倒综合征(EFS)是一种发现于骑士王查尔斯猎犬的犬类发作性高张力障碍。发作是由运动、压力或兴奋引发的，其特征是胸部和骨盆四肢出现渐进性高张力，导致典型的跟踪鹿的姿势和/或崩溃。我们使用全基因组关联策略将EFS基因座定位到犬7号染色体上3.48 Mb的临界区间。通过基于生物学可信程度对候选基因进行优先排序，我们发现编码脑特异性细胞外基质蛋白多糖短链的bcan基因15.7kb缺失与EFS有关。这代表了EFS的一个引人注目的因果突变，因为Brivican在控制突触稳定性和神经传导速度的神经周网络的形成中起着至关重要的作用。缺失断裂点的定位使得多重PCR和多重连接依赖的探针扩增(MLPA)基因分型测试得以发展，可以准确地区分正常动物、携带者和患病动物。对更多没有美国EFS病史的CKCS犬进行的更广泛的测试显示，携带者非常常见(12.9%)。针对EFS基因微缺失的分子遗传学测试的开发将允许实施定向育种计划，旨在最大限度地减少患有EFS的动物数量，并使受影响的狗的确诊诊断和药物治疗成为可能。►阵发性跌倒是一种常染色体隐性遗传性阵发性高张障碍。►我们在犬的7号染色体上定位了一个3.48Mb的片段。►我们在编码短蛋白多糖的bcan基因中发现了一个新的微缺失。►多重聚合酶链式反应和多重聚合酶链式反应检测可以区分正常动物、携带者和患病动物。►bcan突变可能是人类运动性高张障碍的原因。
Episodic falling syndrome (EFS) is a canine paroxysmal hypertonicity disorder found in Cavalier King Charles spaniels. Episodes are triggered by exercise, stress or excitement and characterized by progressive hypertonicity throughout the thoracic and pelvic limbs, resulting in a characteristic 'deer-stalking' position and/or collapse. We used a genome-wide association strategy to map the EFS locus to a 3.48 Mb critical interval on canine chromosome 7. By prioritizing candidate genes on the basis of biological plausibility, we found that a 15.7 kb deletion in BCAN, encoding the brain-specific extracellular matrix proteoglycan brevican, is associated with EFS. This represents a compelling causal mutation for EFS, since brevican has an essential role in the formation of perineuronal nets governing synapse stability and nerve conduction velocity. Mapping of the deletion breakpoint enabled the development of Multiplex PCR and Multiplex Ligation-dependent Probe Amplification (MLPA) genotyping tests that can accurately distinguish normal, carrier and affected animals. Wider testing of a larger population of CKCS dogs without a history of EFS from the USA revealed that carriers are extremely common (12.9%). The development of molecular genetic tests for the EFS microdeletion will allow the implementation of directed breeding programs aimed at minimizing the number of animals with EFS and enable confirmatory diagnosis and pharmacotherapy of affected dogs. ► Episodic falling is a canine autosomal recessive paroxysmal hypertonicity disorder. ► We mapped the episodic falling locus to a 3.48 Mb region on canine chromosome 7. ► We found a novel microdeletion in BCAN encoding the proteoglycan brevican. ► Multiplex PCR and MLPA tests can distinguish normal, carrier and affected animals. ► BCAN mutations may underlie human exercise-induced hypertonicity disorders.
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DOI：
10.1006/bbrc.2000.3583
发表时间：
2000-10-05
影响因子：
3.1
作者：
Hirakawa, S;Oohashi, T;Ninomiya, Y
通讯作者：
Ninomiya, Y
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Drögemüller C;Becker D;Brunner A;Haase B;Kircher P;Seeliger F;Fehr M;Baumann U;Lindblad-Toh K;Leeb T
通讯作者：
Leeb T
影响因子：
30.8
作者：
SHIANG, R;RYAN, SG;WASMUTH, JJ
通讯作者：
WASMUTH, JJ
影响因子：
14.9
作者：
Schouten, JP;McElgunn, CJ;Pals, G
通讯作者：
Pals, G