Mapping of equine cerebellar abiotrophy to ECA2 and identification of a potential causative mutation affecting expression of MUTYH
Mapping of equine cerebellar abiotrophy to ECA2 and identification of a potential causative mutation affecting expression of MUTYH
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DOI：
10.1016/j.ygeno.2010.11.006
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发表时间：
2011-02-01
期刊：
影响因子：
4.4
通讯作者：
Penedo, M. Cecilia T.
中科院分区：
文献类型：
--
作者：
Brault, Leah S.;Cooper, Caitlin A.;Penedo, M. Cecilia T.
马小脑萎缩症（英语：Cerebellar Abiotrophy）是一种在阿拉伯马中发现的神经系统疾病。CA的特征在于小脑浦肯野细胞的出生后变性。CA的症状包括共济失调、头部震颤和缺乏平衡。我们已经发现了一个连锁的CA表型ECA2上的微卫星标记，并确定了一个保守的纯合性跨越约142 kb的区域。对该区域的四个基因进行完整测序，发现了一个仅在阿拉伯马中发现的SNP，位于TOE1的外显子4和MUTYH上游约1200个碱基对，邻近转录因子GATA 2的可能结合位点。来自受影响和未受影响的马的小脑的cDNA的qPCR分析表明，MUTYH表达在受影响的马中下调。因此，该SNP可能对TOE1具有功能效应，或通过负面影响GATA 2的结合亲和力对MUTYH具有调节效应。(C)2010年爱思唯尔公司All rights reserved.
Equine Cerebellar Abiotrophy (CA) is a neurological disease found in Arabian horses. CA is characterized by post-natal degeneration of the Purkinje cells of the cerebellum. Signs of CA include ataxia, head tremors, and a lack of balance equilibrium. We have discovered a linkage of the CA phenotype to a microsatellite marker on ECA2 and identified a region of conserved homozygosity spanning approximately 142 kb. Complete sequencing of the four genes in this region identified one SNP found only in Arabian horses, located in exon 4 of TOE1 and approximately 1200 base pairs upstream of MUTYH, adjacent to a possible binding site for the transcription factor GATA2. qPCR analysis of cDNA from the cerebella of affected and unaffected horses suggested that MUTYH expression is down-regulated in affected horses. This SNP may therefore have a function effect on TOE1, or a regulatory effect on MUTYH by negatively affecting the binding affinity of GATA2. (C) 2010 Elsevier Inc. All rights reserved.