Departamento de Biologia Geral, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Department of Animal Biosciences, Centre for Genetic Improvement of Livestock, University of Guelph, Guelph, Ontario, Canada.
J Anim Sci. 2018 Dec 3;96(12):4978-4999. doi: 10.1093/jas/sky382.
Reduced bull fertility imposes economic losses in bovine herds. Specifically, testicular and spermatic traits are important indicators of reproductive efficiency. Several genome-wide association studies (GWAS) have identified genomic regions associated with these fertility traits. The aims of this study were as follows: 1) to perform a systematic review of GWAS results for spermatic and testicular traits in cattle and 2) to identify key functional candidate genes for these traits. The identification of functional candidate genes was performed using a systems biology approach, where genes shared between traits and studies were evaluated by a guilt by association gene prioritization (GUILDify and ToppGene software) in order to identify the best functional candidates. These candidate genes were integrated and analyzed in order to identify overlapping patterns among traits and breeds. Results showed that GWAS for testicular-related traits have been developed for beef breeds only, whereas the majority of GWAS for spermatic-related traits were conducted using dairy breeds. When comparing traits measured within the same study, the highest number of genes shared between different traits was observed, indicating a high impact of the population genetic structure and environmental effects. Several chromosomal regions were enriched for functional candidate genes associated with fertility traits. Moreover, multiple functional candidate genes were enriched for markers in a species-specific basis, taurine (Bos taurus) or indicine (Bos indicus). For the different candidate regions identified in the GWAS in the literature, functional candidate genes were detected as follows: B. Taurus chromosome X (BTX) (TEX11, IRAK, CDK16, ATP7A, ATRX, HDAC6, FMR1, L1CAM, MECP2, etc.), BTA17 (TRPV4 and DYNLL1), and BTA14 (MOS, FABP5, ZFPM2). These genes are responsible for regulating important metabolic pathways or biological processes associated with fertility, such as progression of spermatogenesis, control of ciliary activity, development of Sertoli cells, DNA integrity in spermatozoa, and homeostasis of testicular cells. This study represents the first systematic review on male fertility traits in cattle using a system biology approach to identify key candidate genes for these traits.
公牛繁殖力降低会给牛群带来经济损失。具体来说,睾丸和精子特征是生殖效率的重要指标。几项全基因组关联研究(GWAS)已经确定了与这些生育特征相关的基因组区域。本研究的目的如下:1)对牛的精子和睾丸特征的 GWAS 结果进行系统综述,2)鉴定这些特征的关键功能候选基因。使用系统生物学方法鉴定功能候选基因,通过关联基因优先排序(GUILDify 和 ToppGene 软件)评估在不同研究和特征中共享的基因,以鉴定最佳功能候选基因。这些候选基因被整合和分析,以识别特征和品种之间的重叠模式。结果表明,与睾丸相关特征的 GWAS 仅针对肉牛品种进行了开发,而与精子相关特征的大多数 GWAS 则使用奶牛品种进行。当比较同一研究中测量的特征时,观察到不同特征之间共享的基因数量最多,这表明种群遗传结构和环境效应的影响很大。几个染色体区域富含与生育特征相关的功能候选基因。此外,在物种特异性基础上,有多个功能候选基因与标记富集,包括 Taurine(Bos taurus)或 indicine(Bos indicus)。在文献中的 GWAS 中确定了不同的候选区域,检测到了以下功能候选基因:B. Taurus 染色体 X(BTX)(TEX11、IRAK、CDK16、ATP7A、ATRX、HDAC6、FMR1、L1CAM、MECP2 等)、BTA17(TRPV4 和 DYNLL1)和 BTA14(MOS、FABP5、ZFPM2)。这些基因负责调节与生育能力相关的重要代谢途径或生物学过程,例如精子发生的进展、纤毛活动的控制、支持细胞的发育、精子的 DNA 完整性以及睾丸细胞的动态平衡。本研究代表了首次使用系统生物学方法对牛的雄性生育特征进行的系统综述,以鉴定这些特征的关键候选基因。