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

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Iso-Touru , T , Wurmser , C , Venhoranta , H , Hiltpold , M , Savolainen , T , Sironen , A , Fischer , K , Flisikowski , K , Fries , R , Vicente-Carrillo , A , Alvarez-Rodriguez , M , Nagy , S , Mutikainen , M , Peippo , J , Taponen , J , Sahana , G , Guldbrandtsen , B , Simonen , H , Rodriguez-Martinez , H , Andersson , M & Pausch , H 2019 , ' A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle ' , BMC Genomics , vol. 20 , 286 . https://doi.org/10.1186/s12864-019-5628-y

Title: A splice donor variant in CCDC189 is associated with asthenospermia in Nordic Red dairy cattle
Author: Iso-Touru, Terhi; Wurmser, Christine; Venhoranta, Heli; Hiltpold, Maya; Savolainen, Tujia; Sironen, Anu; Fischer, Konrad; Flisikowski, Krzysztof; Fries, Ruedi; Vicente-Carrillo, Alejandro; Alvarez-Rodriguez, Manuel; Nagy, Szabolcs; Mutikainen, Mervi; Peippo, Jaana; Taponen, Juhani; Sahana, Goutam; Guldbrandtsen, Bernt; Simonen, Henri; Rodriguez-Martinez, Heriberto; Andersson, Magnus; Pausch, Hubert
Other contributor: University of Helsinki, Departments of Faculty of Veterinary Medicine
University of Helsinki, Production Animal Medicine
University of Helsinki, Helsinki One Health (HOH)

Date: 2019-04-11
Language: eng
Number of pages: 13
Belongs to series: BMC Genomics
ISSN: 1471-2164
DOI: https://doi.org/10.1186/s12864-019-5628-y
URI: http://hdl.handle.net/10138/311065
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 2.98Mb 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/).
Subject: Male infertility
Immotile sperm
413 Veterinary science

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