title: Mapping and exome sequencing identifies a mutation in the IARS gene as the cause of hereditary perinatal weak calf syndrome.
abstract: We identified an IARS (isoleucyl-tRNA synthetase) c.235G>C (p.Val79Leu) substitution as the causative mutation for neonatal weakness with intrauterine growth retardation (perinatal weak calf syndrome). In Japanese Black cattle, the syndrome was frequently found in calves sired by Bull A. Hence, we employed homozygosity mapping and linkage analysis. In order to identify the perinatal weak calf syndrome locus in a 4.04-Mb region of BTA 8, we analysed a paternal half-sibling family with a BovineSNP50 BeadChip and microsatellites. In this critical region, we performed exome sequencing to identify a causative mutation. Three variants were detected as possible candidates for causative mutations that were predicted to disrupt the protein function, including a G>C (p.Val79Leu) mutation in IARS c.235. The IARS c.235G>C mutation was not a homozygous risk allele in the 36 healthy offspring of Bull A. Moreover, the IARS Val79 residue and its flanking regions were evolutionarily and highly conserved. The IARS mutant (Leu79) had decreased aminoacylation activity. Additionally, the homozygous mutation was not found in any of 1526 healthy cattle. Therefore, we concluded that the IARS c.235G>C mutation was the cause of hereditary perinatal weak calf syndrome.
authors.affiliation: Shirakawa Institute of Animal Genetics, Fukushima, Japan. t3hirano@nodai.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirano
authors.forename: Naohiko
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Tamako
authors.initials: T
authors.lastname: Matsuhashi
authors.forename: Daisaku
authors.initials: D
authors.lastname: Watanabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.forename: Akiko
authors.initials: A
authors.lastname: Takasuga
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sugimoto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics*; D002874:Chromosome Mapping; D059472:Exome; D005317:Fetal Growth Retardation / Q000662:veterinary*; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D007533:Isoleucine-tRNA Ligase / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D018908:Muscle Weakness / Q000662:veterinary*; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D013577:Syndrome
chemical_list: D007533:Isoleucine-tRNA Ligase