title: Identification of the bovine Arachnomelia mutation by massively parallel sequencing implicates sulfite oxidase (SUOX) in bone development.
abstract: 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.
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Berne, Switzerland.
authors.forename: Cord
authors.initials: C
authors.lastname: Drögemüller
authors.forename: Jens
authors.initials: J
authors.lastname: Tetens
authors.forename: Snaevar
authors.initials: S
authors.lastname: Sigurdsson
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Gentile
authors.forename: Stefania
authors.initials: S
authors.lastname: Testoni
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.forename: Tosso
authors.initials: T
authors.lastname: Leeb
mesh_terms: D000818:Animals; D001483:Base Sequence; D001846:Bone Development; D002417:Cattle / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D002418:Cattle Diseases / Q000201:enzymology* / Q000235:genetics; D018389:Codon, Nonsense; D005260:Female; D030342:Genetic Diseases, Inborn / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017422:Sequence Analysis, DNA; D050876:Sulfite Oxidase / Q000235:genetics* / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; D050876:Sulfite Oxidase