Syndrome of arachnomelia in Simmental cattle

Buitkamp, Johannes; Luntz, Bernhard; Emmerling, Reiner; Reichenbach, Horst-Dieter; Weppert, Myriam; Schade, Benjamin; Meier, Norbert; Götz, Kay-Uwe

doi:10.1186/1746-6148-4-39

Cited by 17 publications

(30 citation statements)

References 4 publications

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“…The cardinal pathological changes are skeletal malformations of the skull, legs and the spinal column [2]. The facial deformation leads to brachygnathia inferior and concave rounding of the maxilla forming a dent ('pointer-head').…”

Section: Introductionmentioning

confidence: 99%

Arachnomelia syndrome in Simmental cattle is caused by a homozygous 2-bp deletion in the molybdenum cofactor synthesis step 1 gene (MOCS1)

2011

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BackgroundArachnomelia 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.ResultsBy 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.ConclusionsMOCS1 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 protein translation provide strong evidence for the causality of the MOCS1 mutation. Our results are the first example for an oligogenic lethal inherited disease in cattle. Furthermore, they show the potential involvement of sulfite metabolism in aberrant bone development.

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Section: Introductionmentioning

confidence: 99%

Arachnomelia syndrome in Simmental cattle is caused by a homozygous 2-bp deletion in the molybdenum cofactor synthesis step 1 gene (MOCS1)

2011

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“…An outbreak of arachnomelia with hundreds of cases occurred during the 1980s after extensive world-wide usage of a highly selected artificial insemination sire in the international Brown Swiss cattle population [2]. In the past few years, a comparable outbreak of arachnomelia occurred in German Fleckvieh cattle [4]. Different genes seem to be responsible for the arachnomelia disease in these two cattle breeds, as there is no relationship between the founder animals and recently two independent loci were genetically mapped to different chromosomes [6], [7].…”

Section: Introductionmentioning

confidence: 99%

Identification of the Bovine Arachnomelia Mutation by Massively Parallel Sequencing Implicates Sulfite Oxidase (SUOX) in Bone Development

et al. 2010

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Arachnomelia is a monogenic recessive defect of skeletal development in cattle. The causative mutation was previously mapped to a ∼7 Mb interval on chromosome 5. Here we show that array-based sequence capture and massively parallel sequencing technology, combined with the typical family structure in livestock populations, facilitates the identification of the causative mutation. We re-sequenced the entire critical interval in a healthy partially inbred cow carrying one copy of the critical chromosome segment in its ancestral state and one copy of the same segment with the arachnomelia mutation, and we detected a single heterozygous position. The genetic makeup of several partially inbred cattle provides extremely strong support for the causality of this mutation. The mutation represents a single base insertion leading to a premature stop codon in the coding sequence of the SUOX gene and is perfectly associated with the arachnomelia phenotype. Our findings suggest an important role for sulfite oxidase in bone development.

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“…In addition to single unrelated cases of arachnomelia-affected Holstein cattle, recessive inherited arachnomelia was initially reported in German Fleckvieh cattle (Rieck and Schade 1975). Recently, more than 140 cases of arachnomelia-affected calves were reported in the Bavarian Simmental population which all traced back to a single founder (Buitkamp et al 2008). An outbreak of arachnomelia in the European Brown cattle population occurred during the 1980 s after the improvement of the local Brown cattle breeds by extensive usage of highly selected American Brown Swiss sires (Brem et al 1984;König et al 1987;Lidauer and Essl 1994).…”

Section: Introductionmentioning

confidence: 99%

Arachnomelia in Brown Swiss cattle maps to chromosome 5

et al. 2008

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Arachnomelia in Brown Swiss cattle is a monogenic autosomal recessive inherited congenital disorder of the skeletal system giving affected calves a spidery look (OMIA ID 000059). Over a period of 20 years 15 cases were sampled in the Swiss and Italian Brown cattle population. Pedigree data revealed that all affected individuals trace back to a single acknowledged carrier founder sire. A genome scan using 240 microsatellites spanning the 29 bovine autosomes showed homozygosity at three adjacent microsatellite markers on bovine Chr 5 in all cases. Linkage analysis confirmed the localization of the arachnomelia mutation in the region of the marker ETH10. Finemapping and haplotype analysis using a total of 34 markers in this region refined the critical region of the arachnomelia locus to a 7.19-Mb interval on bovine Chr 5. The diseaseassociated IBD haplotype was shared by 36 proven carrier animals and allows marker-assisted selection. As the corresponding human and mouse chromosome segments do not contain any clear functional candidate genes for this disorder, the mutation causing arachnomelia in the Brown Swiss cattle might help to identify an unknown gene in bone development.

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Syndrome of arachnomelia in Simmental cattle

Cited by 17 publications

References 4 publications

Arachnomelia syndrome in Simmental cattle is caused by a homozygous 2-bp deletion in the molybdenum cofactor synthesis step 1 gene (MOCS1)

Arachnomelia syndrome in Simmental cattle is caused by a homozygous 2-bp deletion in the molybdenum cofactor synthesis step 1 gene (MOCS1)

Identification of the Bovine Arachnomelia Mutation by Massively Parallel Sequencing Implicates Sulfite Oxidase (SUOX) in Bone Development

Arachnomelia in Brown Swiss cattle maps to chromosome 5

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