Animal Genomics, Institute of Agricultural Sciences, ETH Zürich, Universitätstrasse 2, 8092, Zürich, Switzerland.
Clinic of Reproductive Medicine, Vetsuisse Faculty, University of Zürich, Winterthurerstrasse 260, 8057, Zürich, Switzerland.
Genet Sel Evol. 2022 Mar 7;54(1):18. doi: 10.1186/s12711-022-00710-0.
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 × 10 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.
为确保公牛的高生育能力，人工授精时会对精液质量和授精效果进行监测。只有符合最低质量要求的精液才会被处理，最终用于人工授精。我们检查了 1343 头瑞士褐牛的 70990 个精液样本，以确定因精液质量低而被拒收的公牛。该程序确定了一头公牛，其 12 个精液样本中的精子数量异常少（每毫升 0.2 ± 0.2×10 个精子），由于多种形态异常，大多数精子都不动。
对这头公牛的基因组进行了 12×的测序，以调查可能的遗传原因。将这头公牛的序列变异基因型与 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 个碱基缺失，这是一个引人注目的候选致病变异。该 1 个碱基缺失导致翻译时移码和提前终止密码子（ENSBTAP00000018337.1:p.Cys1644AlafsTer52）。对 76 头公牛的睾丸转录组进行分析显示，带有提前终止密码子的转录本会发生无意义介导的 mRNA 降解。该 1 个碱基缺失位于包含 181 个单核苷酸多态性（SNP）的 675-kb 单倍型中，该单倍型在瑞士褐牛群体中的频率为 5%。我们的分析还发现另一头公牛在纯合状态下携带该 1 个碱基缺失。第二头公牛的精液分析证实精子浓度低，精子不动，形态异常多，主要影响精子鞭毛，其次影响精子头部。
牛 QRICH2 基因的隐性失活等位基因可能导致精子浓度低，精子不动，形态异常多。常规精子分析可明确鉴定该等位基因的纯合公牛。可以实施直接的基因测试来监测牛群中不良等位基因的频率。
