DNA methylation biomarkers of fertility in bulls

奶牛的生育力已经成为一个真实的问题，尽管在遗传选择方面取得了进展，以减轻这种表型。轻度不孕症患病率增加的一个可能解释可能是表观遗传编程，它将在遗传编程之外发挥作用。表观遗传效应的分子基础是DNA甲基化的稳定性，它通过复制在细胞间传递。事实上，我们是世界上少数几个在牛DNA甲基化分析方面拥有广泛专业知识的研究小组之一，该研究可用于研究基因与环境的相互作用及其对下一代的潜在影响。现在在啮齿动物、绵羊和奶牛中已经充分证明，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以产生睾丸中具有特定表观基因组的公牛，导致对精子的直接影响损害生育力或受影响的胚胎，导致女儿的表型改变。为了筛选这样的缩影，重要的是要比较相对较多的公牛，但要去除与个体相关的个体差异。为了实现这一任务，我们将分析100头公牛的精子样品，根据2个表型，公牛的生育力和女儿的生育力，可以识别与表型相关的代际生物标志物。公牛将使用一种新的DNA捕获方法进行对比，然后进行测序，以根据表型鉴定DNA甲基化变化。 然后焦磷酸测序将用于验证与生育力相关的特定生物标志物。然后将对这些标记进行检测。而不是水泥来测试出生时的诊断潜力。 ******

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. ******