Activation of cryptic splicing in bovine WDR19 is associated with reduced semen quality and male fertility

Autoři: Maya Hiltpold aff001;  Guanglin Niu aff002;  Naveen Kumar Kadri aff001;  Danang Crysnanto aff001;  Zih-Hua Fang aff001;  Mirjam Spengeler aff003;  Fritz Schmitz-Hsu aff004;  Christian Fuerst aff005;  Hermann Schwarzenbacher aff005;  Franz R. Seefried aff003;  Frauke Seehusen aff006;  Ulrich Witschi aff004;  Angelika Schnieke aff002;  Ruedi Fries aff007;  Heinrich Bollwein aff008;  Krzysztof Flisikowski aff002;  Hubert Pausch aff001
Působiště autorů: Animal Genomics, ETH Zürich, Lindau, Switzerland aff001;  Livestock Biotechnology, TU München, Freising, Germany aff002;  QualitasAG, Zug, Switzerland aff003;  Swissgenetics, Zollikofen, Switzerland aff004;  ZuchtData, Wien, Austria aff005;  Institute of Veterinary Pathology, University of Zurich, Zurich, Switzerland aff006;  Animal Breeding, TU München, Freising, Germany aff007;  Clinic of Reproductive Medicine, University of Zurich, Zürich, Switzerland aff008
Vyšlo v časopise: Activation of cryptic splicing in bovine WDR19 is associated with reduced semen quality and male fertility. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008804
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008804


Cattle are ideally suited to investigate the genetics of male reproduction, because semen quality and fertility are recorded for all ejaculates of artificial insemination bulls. We analysed 26,090 ejaculates of 794 Brown Swiss bulls to assess ejaculate volume, sperm concentration, sperm motility, sperm head and tail anomalies and insemination success. The heritability of the six semen traits was between 0 and 0.26. Genome-wide association testing on 607,511 SNPs revealed a QTL on bovine chromosome 6 that was associated with sperm motility (P = 2.5 x 10−27), head (P = 2.0 x 10−44) and tail anomalies (P = 7.2 x 10−49) and insemination success (P = 9.9 x 10−13). The QTL harbors a recessive allele that compromises semen quality and male fertility. We replicated the effect of the QTL on fertility (P = 7.1 x 10−32) in an independent cohort of 2481 Brown Swiss bulls. The analysis of whole-genome sequencing data revealed that a synonymous variant (BTA6:58373887C>T, rs474302732) in WDR19 encoding WD repeat-containing protein 19 was in linkage disequilibrium with the fertility-associated haplotype. WD repeat-containing protein 19 is a constituent of the intraflagellar transport complex that is essential for the physiological function of motile cilia and flagella. Bioinformatic and transcription analyses revealed that the BTA6:58373887 T-allele activates a cryptic exonic splice site that eliminates three evolutionarily conserved amino acids from WDR19. Western blot analysis demonstrated that the BTA6:58373887 T-allele decreases protein expression. We make the remarkable observation that, in spite of negative effects on semen quality and bull fertility, the BTA6:58373887 T-allele has a frequency of 24% in the Brown Swiss population. Our findings are the first to uncover a variant that is associated with quantitative variation in semen quality and male fertility in cattle.

Klíčová slova:

Cattle – Haplotypes – Heredity – Insemination – Semen – Sperm – Sperm head – Variant genotypes


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Genetika Reprodukční medicína

Článek vyšel v časopise

PLOS Genetics

2020 Číslo 5

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