A frameshift mutation in ARMC3 is associated with a tail stump sperm defect in Swedish Red (Bos taurus) cattle

Pausch, Hubert; Venhoranta, Heli; Wurmser, Christine; Hakala, Kristo; Iso-Touru, Terhi; Sironen, Anu; Vingborg, R. K. K.; Lohi, Hannes; Söderquist, L.; Fries, R.; Andersson, Maria

doi:10.1186/s12863-016-0356-7

Cited by 40 publications

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“…It is well known that bulls suffering from undetected diseases and stress may temporarily produce ejaculates that do not fulfill the requirements for artificial insemination [51,52]. Bulls that produce ejaculates of low quality despite being healthy might carry rare genetic variants that can be identified using case-control association testing [39,40]. We considered only ejaculates that fulfill minimum requirements for AI to avoid false-positive association signal arising from phenotypic outliers [53].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, it is important to emphasize that homozygous bulls are not infertile. Therefore, the consequences of the BTA6 haplotype on male reproduction are less detrimental than, e.g., of recessive haplotypes that compromise semen quality and lead to male infertility [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

“…Records for which either the interval between successive ejaculates or the semen collector were missing were excluded from our analysis. We retained only ejaculates that complied with minimum requirements for artificial insemination because insufficient semen quality might be attributable to rare genetic conditions [38,39]. Eventually, we retained only ejaculates of bulls for which at least 8 ejaculates were available.…”

Section: Semen Quality Data Of Swiss Bsw Bullsmentioning

confidence: 99%

“…Case-control association studies uncovered recessive variants in the TMEM95, ARMC3 and CCDC189 genes, that compromise semen quality and male fertility in the homozygous state [38][39][40].…”

Section: Introductionmentioning

confidence: 99%

“…However, the effect of the missense variant on bull fertility was not validated in two independent populations [37]. Case-control association studies uncovered recessive variants in the TMEM95, ARMC3 and CCDC189 genes, that compromise semen quality and bull fertility in the homozygous state [38][39][40].…”

Section: Introductionmentioning

confidence: 99%

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Activation of cryptic splicing in bovineWDR19is associated with reduced semen quality and male fertility

Hiltpold

Niu²,

Kadri

et al. 2020

Preprint

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Cattle are uniquely suited to investigate the genetics of male reproduction disorders, as semen quality and fertility are recorded for all ejaculates of artificial insemination bulls. Using 26,090 ejaculates of 794 Brown Swiss bulls, we analysed ejaculate volume, sperm concentration, sperm motility, sperm head and tail anomalies, and bull fertility. The heritability of the six semen traits was between 0 and 0.26. Genome-wide association testing between semen quality and 607,511 SNPs reveaed 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 2481 bulls from an independent cohort of 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 showed that the BTA6:58373887 T-allele activates a cryptic splice site that eliminates three evolutionarily conserved amino acids from the WD-repeat domain, thus reducing semen quality and fertility. Western blot analysis demonstrated that the BTA6:58373887 T-allele decreases the WDR19 protein expression. We make the remarkable observation that, in spite of negative effects on semen quality and bull fertility, the deleterious allele has a frequency of 24 % in the Brown Swiss population. Our findings are the first to uncover a variant that controls quantitative variation in semen quality and male fertility in cattle. Author summaryMale reproductive disorders occur in many species. In cattle farming, artificial insemination is widely used. To ensure high fertilization rates, the quality of each ejaculate is recorded and the insemination success is monitored for every artificial insemination bull. We analyse semen quality and microarray-called genotypes at more than 600,000 genome-wide SNP markers in 794 bulls to identify a recessive allele that compromises semen quality and fertility. We take advantage of whole-genome sequencing to pinpoint a variant in the coding sequence of WDR19 encoding WD repeat-containing protein 19 that activates a novel exonic splice site. Our results indicate that cryptic splicing in WDR19 is associated with reduced male reproductive performance in cattle. This is the first report to reveal a variant associated with quantitative variation in bovine semen quality.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Semen Quality Data Of Swiss Bsw Bullsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activation of cryptic splicing in bovineWDR19is associated with reduced semen quality and male fertility

Hiltpold

Niu²,

Kadri

et al. 2020

Preprint

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Sperm morphometry is affected by increased inbreeding in the Retinta cattle breed: A molecular approach

Teran

Azcona

Ramón

et al. 2021

Molecular Reproduction Devel

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The effect of inbreeding depression on sperm motility is well documented, but its influence on sperm morphometry has been scarcely examined to date. Here, we combined the use of computer‐assisted sperm morphometry analysis (CASMA) with a SNP‐based genomic approach to determine and characterize the effect of inbreeding on the sperm shape of a highly inbred cattle population. We determined seven morphometric parameters on frozen‐thawed sperm samples of 57 Retinta bulls: length (L, µm), width (W, µm), area (A, µm2), perimeter (P, µm), ellipticity (ELI; L/W), elongation (L−W)/(L + W) and perimeter‐to‐area shape factor (p2a; P2/4 × π × A). The comparison of highly inbred (HI) and lowly inbreed (LI) individuals based on runs of homozygosity (ROH) inbreeding values (F ROH) showed no differences between groups. An additional two‐step unsupervised sperm subpopulation analysis based on morphometric parameters showed significant differences in the abundance of different sperm subpopulations between groups (p < 0.05). This analysis revealed that HI bulls harbored a higher percentage of narrow‐head sperm as opposed to the higher percentage of large‐ and round‐headed sperm detected in LI. A further genomic characterization revealed 23 regions differentially affected by inbreeding in both groups, detecting six genes (SPAG6, ARMC3, PARK7, VAMP3, DYNLRB2, and PHF7) previously related to different spermatogenesis‐associated processes.

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Metazoan evolution of the armadillo repeat superfamily

Gul

Hulpiau

Saeys

et al. 2016

Cell. Mol. Life Sci.

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The superfamily of armadillo repeat proteins is a fascinating archetype of modular-binding proteins involved in various fundamental cellular processes, including cell-cell adhesion, cytoskeletal organization, nuclear import, and molecular signaling. Despite their diverse functions, they all share tandem armadillo (ARM) repeats, which stack together to form a conserved three-dimensional structure. This superhelical armadillo structure enables them to interact with distinct partners by wrapping around them. Despite the important functional roles of this superfamily, a comprehensive analysis of the composition, classification, and phylogeny of this protein superfamily has not been reported. Furthermore, relatively little is known about a subset of ARM proteins, and some of the current annotations of armadillo repeats are incomplete or incorrect, often due to high similarity with HEAT repeats. We identified the entire armadillo repeat superfamily repertoire in the human genome, annotated each armadillo repeat, and performed an extensive evolutionary analysis of the armadillo repeat proteins in both metazoan and premetazoan species. Phylogenetic analyses of the superfamily classified them into several discrete branches with members showing significant sequence homology, and often also related functions. Interestingly, the phylogenetic structure of the superfamily revealed that about 30 % of the members predate metazoans and represent an ancient subset, which is gradually evolving to acquire complex and highly diverse functions.

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A frameshift mutation in ARMC3 is associated with a tail stump sperm defect in Swedish Red (Bos taurus) cattle

Cited by 40 publications

References 43 publications

Activation of cryptic splicing in bovineWDR19is associated with reduced semen quality and male fertility

Activation of cryptic splicing in bovineWDR19is associated with reduced semen quality and male fertility

Sperm morphometry is affected by increased inbreeding in the Retinta cattle breed: A molecular approach

Metazoan evolution of the armadillo repeat superfamily

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