Semen quality and insemination success are monitored in artificial insemination bulls to ensure high male fertility rates. Only ejaculates that fulfill minimum quality requirements are processed and eventually used for artificial inseminations. We examined 70,990 ejaculates from 1343 Brown Swiss bulls to identify bulls from which all ejaculates were rejected due to low semen quality. This procedure identified a bull that produced 12 ejaculates with an aberrantly small number of sperm (0.2 ± 0.2 × 109 sperm per mL) which were mostly immotile due to multiple morphological abnormalities. The genome of this bull was sequenced at a 12× coverage to investigate a possible genetic cause. Comparing the sequence variant genotypes of this bull with those from 397 fertile bulls revealed a 1-bp deletion in the coding sequence of the QRICH2 gene which encodes the glutamine rich 2 protein, as a compelling candidate causal variant. This 1-bp deletion causes a frameshift in translation and a premature termination codon (ENSBTAP00000018337.1:p.Cys1644AlafsTer52). The analysis of testis transcriptomes from 76 bulls showed that the transcript with the premature termination codon is subject to nonsense-mediated mRNA decay. The 1-bp deletion resides in a 675-kb haplotype that includes 181 single nucleotide polymorphisms (SNPs) from the Illumina BovineHD Bead chip. This haplotype segregates at a frequency of 5% in the Brown Swiss cattle population. Our analysis also identified another bull that carried the 1-bp deletion in the homozygous state. Semen analyses from the second bull confirmed low sperm concentration and immotile sperm with multiple morphological abnormalities that primarily affect the sperm flagellum and, to a lesser extent, the sperm head. A recessive loss-of-function allele of the bovine QRICH2 gene likely causes low sperm concentration and immotile sperm with multiple morphological abnormalities. Routine sperm analyses unambiguously identify homozygous bulls for this allele. A direct gene test can be implemented to monitor the frequency of the undesired allele in cattle populations.

中文翻译：

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牛 QRICH2 中的 1-bp 缺失导致精子数量低和精子不动并伴有多种形态异常


对人工授精公牛的精液质量和授精成功率进行监测，以确保高雄性生育率。只有满足最低质量要求的精液才会被处理并最终用于人工授精。我们检查了 1343 头棕色瑞士公牛的 70,990 份精液，以确定哪些公牛因精液质量低而导致所有精液被拒绝。该程序鉴定出一头公牛产生了 12 次精液，精子数量异常少（每毫升 0.2 ± 0.2 × 109 个精子），由于多种形态异常，这些精子大多不动。对这头公牛的基因组进行了 12 倍覆盖率的测序，以研究可能的遗传原因。将这头公牛的序列变异基因型与来自 397 头可育公牛的序列变异基因型进行比较，发现编码富含谷氨酰胺 2 蛋白的 QRICH2 基因的编码序列中存在 1 bp 缺失，这是一个令人信服的候选因果变异。此 1-bp 删除会导致翻译移码和过早终止密码子 (ENSBTAP00000018337.1:p.Cys1644AlafsTer52)。对 76 头公牛睾丸转录组的分析表明，带有提前终止密码子的转录本会受到无义介导的 mRNA 衰减。 1 bp 缺失位于 675 kb 单倍型中，该单倍型包含来自 Illumina BovineHD Bead 芯片的 181 个单核苷酸多态性 (SNP)。这种单倍型在瑞士褐牛群体中的分离频率为 5%。我们的分析还发现了另一头在纯合状态下携带 1-bp 缺失的公牛。第二头公牛的精液分析证实精子浓度低且精子不动，具有多种形态异常，主要影响精子鞭毛，并在较小程度上影响精子头。 牛 QRICH2 基因的隐性功能丧失等位基因可能会导致精子浓度低和精子不动，并伴有多种形态异常。常规精子分析可以明确识别该等位基因的纯合公牛。可以实施直接基因测试来监测牛群中不需要的等位基因的频率。