Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Hiltpold M

PROVIDER: S-EPMC7252675 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Hiltpold Maya M Niu Guanglin G Kadri Naveen Kumar NK Crysnanto Danang D Fang Zih-Hua ZH Spengeler Mirjam M Schmitz-Hsu Fritz F Fuerst Christian C Schwarzenbacher Hermann H Seefried Franz R FR Seehusen Frauke F Witschi Ulrich U Schnieke Angelika A Fries Ruedi R Bollwein Heinrich H Flisikowski Krzysztof K Pausch Hubert H

PLoS genetics 20200514 5

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 chromoso ...[more]

PMID: 32407316

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Dataset Information

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

Publications

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

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