Identification of a doublet missense substitution in the bovine LRP4 gene as a candidate causal mutation for syndactyly in Holstein cattle
Identification of a doublet missense substitution in the bovine LRP4 gene as a candidate causal mutation for syndactyly in Holstein cattle
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DOI：
10.1016/j.ygeno.2006.05.007
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发表时间：
2006-11-01
期刊：
影响因子：
4.4
通讯作者：
Eggen, A.
中科院分区：
文献类型：
--
作者：
Duchesne, A.;Gautier, M.;Eggen, A.
荷斯坦牛并指畸形是一种常染色体隐性异常，其特征是功能性趾融合。这种疾病先前已被映射到牛15号染色体的端粒部分。在这里，我们描述了在荷斯坦牛并指畸形的精细映射到3.5 Mb的关键间隔使用比较映射方法和胚胎移植产生的扩展谱系。我们报告的遗传学证据排除两个基因以前建议作为候选人（EXT2和ALX4），并描述了一个双联体突变的鉴定在一个基因的关键间隔：LRP 4与并指完全连锁不平衡。最后，根据最近的发现，关于小鼠突变体丹和mdig和小鼠敲除LRP 4，我们提出了坚实的证据，随后在LRP 4外显子33的取代是一个强有力的候选人的因果突变并指在荷斯坦牛。(c)2006爱思唯尔公司All rights reserved.
Syndactyly in Holstein cattle is an autosomal recessive abnormality characterized by the fusion of the functional digits. This disorder has been previously mapped to the telomeric part of bovine chromosome 15. Here, we describe the fine-mapping of syndactyly in Holstein cattle to a 3.5-Mb critical interval using a comparative mapping approach and an extended pedigree generated by embryo transfer. We report genetic evidence for the exclusion of two genes previously suggested as candidates (EXT2 and ALX4) and describe the identification of a doublet mutation in complete linkage disequilibrium with syndactyly in one gene of the critical interval: LRP4. Finally, based on recent discoveries concerning the mouse mutants dan and mdig and a mouse knockout for Lrp4, we present solid evidence that the subsequent substitution in LRP4 exon 33 is a strong candidate causal mutation for syndactyly in Holstein cattle. (c) 2006 Elsevier Inc. All rights reserved.