DNA methylation biomarkers of fertility in bulls

公牛生育能力的 DNA 甲基化生物标志物

• 批准号: 525065-2018
• 负责人: Sirard, MarcAndré
• 金额: $ 2.53万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=697441
• 关键词: DNA; methylation; biomarkers; fertility; bulls

Fertility in dairy cows has become a real concern despite the progression made in genetic selection to alleviate this phenotype. One of the possible explanations for the increased prevalence of mild infertility could be the epigenetic programming that would act in addition to genetic programming. The molecular basis for epigenetic effect is the stability of DNA methylation which is transmitted from cells to cells through replication. We are actually one of the few research groups in the world with extensive expertise in bovine DNA methylation analysis which could be used to study gene-environment interaction and the potential impact on the next generation. It is now well demonstrated in rodents, sheep and cows that the phenomena may impact the next generation fertility. It is also well demonstrated in mammals that the male environment can influence the phenotype of the offspring. Therefore, the hypothesis is that metabolically stressed females could generate bulls with a particular epigenome in their testis resulting in either a direct effect on the sperm impairing fertility or affected embryos resulting in a modified phenotype in the daughter. To screen for such epitome, it would be important to compare a relatively high number of bulls but removing the individual variations associated with individuals. To achieve such a task, we will analyze sperm samples from 100 bulls according to 2 phenotypes, bull's fertility and daughter's fertility which could identify intergenerational biomarkers associated with the phenotype. Bulls will be contrasted using a new DNA capture approach followed by sequencing to identify DNA methylation changes according to phenotypes. Then pyrosequencing will be used to validate specific biomarkers associated with fertility. These markers will then be tested. on blood and hair instead of cement to test a diagnostic potential at birth.

尽管在遗传选择方面取得了进展，以减轻这种表型，但奶牛的生育力已成为一个真正的问题。轻度不孕症发病率增加的一个可能的解释是，表观遗传程序除了遗传程序外，还会起作用。表观遗传效应的分子基础是DNA甲基化的稳定性，这种甲基化通过复制在细胞间传递。我们实际上是世界上为数不多的在牛DNA甲基化分析方面拥有广泛专业知识的研究小组之一，该分析可用于研究基因-环境相互作用及其对下一代的潜在影响。现在在啮齿类动物、羊和牛身上得到了很好的证明，这种现象可能会影响下一代的生育能力。在哺乳动物中也充分证明，雄性环境可以影响后代的表型。因此，假设是，代谢应激的雌性可能会在其睾丸中产生具有特定表观基因组的公牛，从而直接影响精子的生育能力，或者影响胚胎，导致女儿的表型改变。为了筛选这样的缩影，重要的是比较相对较多的公牛，但去除与个体相关的个体差异。为了完成这项任务，我们将根据两种表型，公牛的生育能力和女儿的生育能力来分析100头公牛的精子样本，这可以识别与表型相关的代际生物标志物。公牛将使用新的DNA捕获方法进行对比，随后进行测序，以根据表型确定DNA甲基化变化。然后焦磷酸测序将用于验证与生育相关的特定生物标志物。然后对这些标记进行测试。用血液和头发代替水泥来测试出生时的诊断潜力。