BMC Genomics (Apr 2019)

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

  • Terhi Iso-Touru,
  • Christine Wurmser,
  • Heli Venhoranta,
  • Maya Hiltpold,
  • Tujia Savolainen,
  • Anu Sironen,
  • Konrad Fischer,
  • Krzysztof Flisikowski,
  • Ruedi Fries,
  • Alejandro Vicente-Carrillo,
  • Manuel Alvarez-Rodriguez,
  • Szabolcs Nagy,
  • Mervi Mutikainen,
  • Jaana Peippo,
  • Juhani Taponen,
  • Goutam Sahana,
  • Bernt Guldbrandtsen,
  • Henri Simonen,
  • Heriberto Rodriguez-Martinez,
  • Magnus Andersson,
  • Hubert Pausch

DOI
https://doi.org/10.1186/s12864-019-5628-y
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 13

Abstract

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Abstract 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/).

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