A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle

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  • Terhi Iso-Touru, Natural Resources Institute Finland (Luke)
  • ,
  • Christine Wurmser, Technische Universitat Munchen
  • ,
  • Heli Venhoranta, Helsingin yliopisto
  • ,
  • Maya Hiltpold, ETH Zürich
  • ,
  • Tujia Savolainen, Helsingin yliopisto
  • ,
  • Anu Sironen, Natural Resources Institute Finland (Luke)
  • ,
  • Konrad Fischer, Technische Universitat Munchen
  • ,
  • Krzysztof Flisikowski, Technische Universitat Munchen
  • ,
  • Ruedi Fries, Technische Universitat Munchen
  • ,
  • Alejandro Vicente-Carrillo, Linköping University
  • ,
  • Manuel Alvarez-Rodriguez, Linköping University
  • ,
  • Szabolcs Nagy, University of Pannonia
  • ,
  • Mervi Mutikainen, Natural Resources Institute Finland (Luke)
  • ,
  • Jaana Peippo, Natural Resources Institute Finland (Luke)
  • ,
  • Juhani Taponen, Helsingin yliopisto
  • ,
  • Goutam Sahana
  • Bernt Guldbrandtsen
  • Henri Simonen, VikingGenetics
  • ,
  • Heriberto Rodriguez-Martinez, Linköping University
  • ,
  • Magnus Andersson, Helsingin yliopisto
  • ,
  • Hubert Pausch, ETH Zürich

Background: Cattle populations are highly amenable to the genetic mapping of male reproductive traits because longitudinal data on ejaculate quality and dense microarray-derived genotypes are available for thousands of artificial insemination bulls. Two young Nordic Red bulls delivered sperm with low progressive motility (i.e., asthenospermia) during a semen collection period of more than four months. The bulls were related through a common ancestor on both their paternal and maternal ancestry. Thus, a recessive mode of inheritance of asthenospermia was suspected. Results: Both bulls were genotyped at 54,001 SNPs using the Illumina BovineSNP50 Bead chip. A scan for autozygosity revealed that they were identical by descent for a 2.98 Mb segment located on bovine chromosome 25. This haplotype was not found in the homozygous state in 8557 fertile bulls although five homozygous haplotype carriers were expected (P = 0.018). Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5′ splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40%, thus lacking the flagellar C1a complex subunit C1a-32 that is supposed to modulate the physiological movement of the sperm flagella. The mutant allele occurs at a frequency of 2.5% in Nordic Red cattle. Conclusions: Our study in cattle uncovered that CCDC189 is required for physiological movement of sperm flagella thus enabling active progression of spermatozoa and fertilization. A direct gene test may be implemented to monitor the asthenospermia-associated allele and prevent the birth of homozygous bulls that are infertile. Our results have been integrated in the Online Mendelian Inheritance in Animals (OMIA) database (https://omia.org/OMIA002167/9913/).

OriginalsprogEngelsk
Artikelnummer286
TidsskriftBMC Genomics
Vol/bind20
Nummer1
Antal sider13
ISSN1471-2164
DOI
StatusUdgivet - 2019

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