A single-base change in the tyrosine kinase II domain of ovine FGFR3 causes hereditary chondrodysplasia in sheep
A single-base change in the tyrosine kinase II domain of ovine FGFR3 causes hereditary chondrodysplasia in sheep
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DOI：
10.1111/j.1365-2052.2005.01398.x
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发表时间：
2006-02-01
期刊：
影响因子：
2.4
通讯作者：
Cockett, NE
中科院分区：
文献类型：
--
作者：
Beever, JE;Smit, MA;Cockett, NE
绵羊遗传性软骨发育不良，或蜘蛛羔羊综合征（SLS），是一种遗传性疾病，其特征是严重的骨骼异常，并已导致绵羊生产者的重大经济损失。在这里，我们证明了一个非同义T > A颠换的高度保守的酪氨酸激酶II结构域的位置候选基因，成纤维细胞生长因子受体3（FGFR3），是负责SLS。我们还证明了突变的FGFR3等位基因对长骨长度具有加性效应，这对长期以来认为SLS是作为严格的单基因孟德尔隐性性状遗传的观点提出了质疑。相反，我们认为SLS的表现主要是由突变型FGFR3等位基因的存在决定的，但它也受到动物遗传背景的影响。与导致人类侏儒症的FGFR3突变相反，这种单碱基变化是唯一已知的导致任何物种骨骼过度生长表型的FGFR3天然突变。
Ovine hereditary chondrodysplasia, or spider lamb syndrome (SLS), is a genetic disorder that is characterized by severe skeletal abnormalities and has resulted in substantial economic losses for sheep producers. Here we demonstrate that a non-synonymous T > A transversion in the highly conserved tyrosine kinase II domain of a positional candidate gene, fibroblast growth factor receptor 3 (FGFR3), is responsible for SLS. We also demonstrate that the mutant FGFR3 allele has an additive effect on long-bone length, calling into question the long-standing belief that SLS is inherited as a strict monogenic, Mendelian recessive trait. Instead, we suggest that SLS manifestation is determined primarily by the presence of the mutant FGFR3 allele, but it is also influenced by an animal's genetic background. In contrast to FGFR3 mutations causing dwarfism in humans, this single-base change is the only known natural mutation of FGFR3 that results in a skeletal overgrowth phenotype in any species.