title: A frameshift mutation in ARMC3 is associated with a tail stump sperm defect in Swedish Red (Bos taurus) cattle.
abstract: BACKGROUND
  Artificial insemination is widely used in many cattle breeding programs. Semen samples of breeding bulls are collected and closely examined immediately after collection at artificial insemination centers. Only ejaculates without anomalous findings are retained for artificial insemination. Although morphological aberrations of the spermatozoa are a frequent reason for discarding ejaculates, the genetic determinants underlying poor semen quality are scarcely understood.
  
  
  RESULTS
  A tail stump sperm defect was observed in three bulls of the Swedish Red cattle breed. The spermatozoa of affected bulls were immotile because of severely disorganized tails indicating disturbed spermatogenesis. We genotyped three affected bulls and 18 unaffected male half-sibs at 46,035 SNPs and performed homozygosity mapping to map the fertility disorder to an 8.42 Mb interval on bovine chromosome 13. The analysis of whole-genome re-sequencing data of an affected bull and 300 unaffected animals from eleven cattle breeds other than Swedish Red revealed a 1 bp deletion (Chr13: 24,301,425 bp, ss1815612719) in the eleventh exon of the armadillo repeat containing 3-encoding gene (ARMC3) that was compatible with the supposed recessive mode of inheritance. The deletion is expected to alter the reading frame and to induce premature translation termination (p.A451fs26). The mutated protein is shortened by 401 amino acids (46 %) and lacks domains that are likely essential for normal protein function.
  
  
  CONCLUSIONS
  We report the phenotypic and genetic characterization of a sterilizing tail stump sperm defect in the Swedish Red cattle breed. Exploiting high-density genotypes and massive re-sequencing data enabled us to identify the most likely causal mutation for the fertility disorder in bovine ARMC3. Our results provide the basis for monitoring the mutated variant in the Swedish Red cattle population and for the early identification of infertile animals.
authors.affiliation: Lehrstuhl fuer Tierzucht, Technische Universitaet Muenchen, 85354, Freising, Germany. Hubert.pausch@tierzucht.tum.de.
authors.forename: Hubert
authors.initials: H
authors.lastname: Pausch
authors.affiliation: Department of Production Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 04920, Saarentaus, Finland. heli.venhoranta@helsinki.fi.
authors.forename: Heli
authors.initials: H
authors.lastname: Venhoranta
authors.affiliation: Lehrstuhl fuer Tierzucht, Technische Universitaet Muenchen, 85354, Freising, Germany. Christine.wurmser@tierzucht.tum.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Wurmser
authors.affiliation: Department of Production Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 04920, Saarentaus, Finland. kalle.e.hakala@helsinki.fi.
authors.forename: Kalle
authors.initials: K
authors.lastname: Hakala
authors.affiliation: Natural Resources Institute Finland (Luke), Green Technology, 31600, Jokioinen, Finland. terhi.iso-touru@luke.fi.
authors.forename: Terhi
authors.initials: T
authors.lastname: Iso-Touru
authors.affiliation: Natural Resources Institute Finland (Luke), Green Technology, 31600, Jokioinen, Finland. anu.sironen@luke.fi.
authors.forename: Anu
authors.initials: A
authors.lastname: Sironen
authors.affiliation: Genoskan A/S, 8830, Tjele, Denmark. rkv@genoskan.dk.
authors.forename: Rikke K
authors.initials: RK
authors.lastname: Vingborg
authors.affiliation: Department of Veterinary Biosciences and Research Programs Unit, Molecular Neurology, University of Helsinki and Folkhälsan Research Center, 00290, Helsinki, Finland. hannes.lohi@helsinki.fi.
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
authors.affiliation: Division of Reproduction, Department of Clinical Sciences, Swedish University of Agricultural Sciences, SE-750 07, Uppsala, Sweden. lennart.soderquist@slu.se.
authors.forename: Lennart
authors.initials: L
authors.lastname: Söderquist
authors.affiliation: Lehrstuhl fuer Tierzucht, Technische Universitaet Muenchen, 85354, Freising, Germany. ruedi.fries@tum.de.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Fries
authors.affiliation: Department of Production Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 04920, Saarentaus, Finland. magnus.andersson@helsinki.fi.
authors.forename: Magnus
authors.initials: M
authors.lastname: Andersson
mesh_terms: D000818:Animals; D051186:Armadillo Domain Proteins / Q000235:genetics*; D001947:Breeding; D002417:Cattle / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics; D005298:Fertility / Q000235:genetics; D016368:Frameshift Mutation; D014644:Genetic Variation; D060005:Genotyping Techniques; D006720:Homozygote; D007246:Infertility / Q000175:diagnosis / Q000235:genetics* / Q000662:veterinary; D008297:Male; D055101:Semen Analysis; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology*; D013548:Sweden
chemical_list: D051186:Armadillo Domain Proteins