在新斯科舍省,一种RB1CC1误解变异在子杀退行性脑病变的回收犬
Juyuan Guo1, Garrett Bullock1, Dennis P O'Brien2
1Canine Genetics Laboratory, Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211, USA.
Genes
|March 28, 2025
概括
在RB1CC1基因中的一个遗传变异导致了新斯科舍收费回收犬的退行性脑病,导致神经问题. 这一发现使得基因查能够识别受影响的狗.
科学领域:
- 狗的遗传学 狗的遗传学
- 神经退行性疾病的神经退行性疾病
- 分子生物学分子生物学
背景情况:
- 新斯科舍省收费回收犬受到一种称为退行性脑病变 (DE) 的遗传性神经疾病的影响.
- DE表现为睡眠期间的非自愿运动,认知能力下降,焦虑,感官过敏和强迫行为,伴随着大脑退化.
- 这种品种中DE的分子遗传原因仍未确定.
研究的目的:
- 为了确定导致新斯科舍省子收费回收犬退行性脑病的特定基因突变.
- 建立遗传神经疾病的遗传基础.
主要方法:
- 全基因组测序 (WGS) 在受影响和未受影响的新斯科舍收费回收犬中进行.
- 测序的基因组与参考基因组对齐,并与334只对照犬的WGS数据进行比较.
- 在一个更大的狗队伍中,确定了一种特定的遗传变异并进行基因定型.
主要成果:
- 在RB1CC1基因 (染色体29:4891014) 的第22个异构体中,单独在受影响的狗中发现了一种同卵性误解C>T变异.
- 这种变体预测了RB1CC1蛋白中的p.G1503R氨基酸替代.
- 对2950只狗的基因型鉴定证实了RB1CC1基因型和退行性脑病变表型之间的完全一致.
结论:
- 已识别的RB1CC1变种与新斯科舍省子收费回收犬的退行性脑病症密切相关.
- RB1CC1对于自细胞形成至关重要,这表明受损的自细胞有助于疾病.
- 受影响狗的神经元中的异常溶解体包容支持受损自假说,为与自功能障碍相关的人类疾病提供了一个模型.
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