Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog
Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog
复制标题
DOI：
10.1073/pnas.0506940103
复制
发表时间：
2006-01-31
影响因子：
11.1
通讯作者：
Murphy, KE
中科院分区：
文献类型：
--
作者：
Clark, LA;Wahl, JM;Murphy, KE
山鸟色是在家养狗的皮毛上观察到的一种颜色模式，其特征是稀释的色素斑块。该性状以常染色体不完全显性方式遗传。山鸟色基因杂合或纯合的狗表现出广泛的听觉和眼科异常，这与人类听觉-色素沉着障碍Waardenburg综合征的观察结果相似。至少有五种基因突变已被确定为Waardenburg综合征的病因；然而，所有病例的遗传基础尚未确定。在设得兰牧羊犬的山鸟色表型中发现了一个微卫星标记的连锁不平衡。该标记位于CFA10的一个与HSA12q13保持同源性的区域。人类基因组的这个区域含有SILV，这是一种在哺乳动物色素沉着中很重要的基因。因此，该基因被评估为山鸟色图案的候选基因。在10号内含子/ 11号外显子的边界处发现了一个短的穿插元件插入，并且该插入在多个品种中与山鸟色表型分离。另一个发现是在短穿插元素的寡核苷酸（dA）丰富的尾部缺失。这种缺失允许正常的色素沉着。这些数据表明，SILV负责山鸟色图案，并与听觉和眼科系统的功能受损有关。尽管人类中SILV的突变表型尚不清楚，但这些结果使其成为人类听觉色素沉着障碍的有趣候选基因。
Merle is a pattern of coloring observed in the coat of the domestic dog and is characterized by patches of diluted pigment. This trait is inherited in an autosomal, incompletely dominant fashion. Dogs heterozygous or homozygous for the merle locus exhibit a wide range of auditory and ophthalmologic abnormalities, which are similar to those observed for the human auditory-pigmentation disorder Waardenburg syndrome. Mutations in at least five genes have been identified as causative for Waardenburg syndrome; however, the genetic bases for all cases have not been determined. Linkage disequilibrium was identified for a microsatellite marker with the merle phenotype in the Shetland Sheepdog. The marker is located in a region of CFA10 that exhibits conservation of synteny with HSA12q13. This region of the human genome contains SILV, a gene important in mammalian pigmentation. Therefore, this gene was evaluated as a candidate for merle patterning. A short interspersed element insertion at the boundary of intron 10/exon 11 was found, and this insertion segregates with the merle phenotype in multiple breeds. Another finding was deletions within the oligo(dA)-rich tail of the short interspersed element. Such deletions permit normal pigmentation. These data show that SILV is responsible for merle patterning and is associated with impaired function of the auditory and ophthalmologic systems. Although the mutant phenotype of SILV in the human is unknown, these results make it an intriguing candidate gene for human auditory-pigmentation disorders.