arachnomelia syndrome in simmental cattle is caused by a homozygous 2-bp deletion in the molybdenum cofactor synthesis step 1 gene (mocs1)arachnomelia综合症在西门塔尔牛的牛是由纯合2个基点删除钼辅因子的合成步骤1基因(mocs1).pdfVIP

Buitkamp et al. BMC Genetics 2011, 12:11 /1471-2156/12/11 RESEARCH ARTICLE Open Access Arachnomelia syndrome in Simmental cattle is caused by a homozygous 2-bp deletion in the molybdenum cofactor synthesis step 1 gene (MOCS1) * Johannes Buitkamp , Jördis Semmer, Kay-Uwe Götz Abstract Background: Arachnomelia syndrome is an autosomal recessive inherited disease in cattle. Affected calves die around birth and show malformations of the skeleton mainly affecting the legs, the spinal column and the skull. A number of arachnomelia syndrome affected Simmental calves were recently detected by a surveillance system of anomalies with a peak of more than 120 recorded cases in the year 2006. The causative mutation was previously mapped to a 9 cM-region on bovine chromosome 23. We herein report the fine-mapping and identification of the gene causing arachnomelia syndrome in Simmental cattle. Results: By using a dense set of markers, the arachnomelia syndrome linked region could be refined to 1.5 cM harbouring three protein coding genes. Comparative sequencing of these genes revealed a two-bp-deletion in the bovine MOCS1 gene resulting in a frame-shift and a premature termination codon. We genotyped affected calves and their ancestors and found that all affected were homozygous for the deletion whereas all carriers were heterozygous. Furthermore, cattle from the same population, but not directly related to known carriers mostly showed the wild type genotype. Conclusions: MOCS1 encodes two proteins that are involved in the first synthesis step of molybdenum cofactor. A non functional sulfite-oxydase, one of the enzymes requiring molybdenum cofactor, leads to a similar pathology in Brown Swiss cattle. In combination the perfect association of the mutation with the phenotype and the obvious disruption of p