Modular workflow for the community-led development of custom livestock DNA methylation arrays

用于社区主导的定制牲畜 DNA 甲基化阵列开发的模块化工作流程

• 批准号: BB/W019051/1
• 负责人: Albert Tenesa
• 金额: $ 44.85万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW019051%2F1
• 关键词: Modular; workflow; community; led; development

Epigenetic marks are changes on the genome that do not involve DNA sequence alterations. A commonly studied epigenetic mark is DNA methylation, that affects how genes are expressed and has been linked to diseases and other traits in both humans and animals. DNA methylation can determine if a particular gene is switched on (expressed) or not in a particular tissue. Research has shown that, unlike the DNA sequence, DNA methylation can also act as a record of the environment we are exposed to. For example, some DNA methylation "sites" can distinguish smokers from never-smokers, animals with different nutritional states or fertility.Currently investigating DNA methylation is only possible through the use of expensive sequencing technologies, and this excessive cost prevents scientists from studying DNA methylation in livestock and how it could contribute to informing selection strategies to breed healthy and productive animals effectively and sustainably. The project we propose will develop the tools to enable these studies. We have engaged with leaders in the field of livestock epigenetics, industrial partners and breeders forming a truly multidisciplinary team with a common goal. As there are multiple livestock species we propose to develop the computational tools to select the most informative DNA methylation "sites" to test in an epigenetic kit similar to the direct-to-consumer genetic testing kits. This epigenetic test done using DNA methylation arrays (kits), is substantially cheaper than obtaining the DNA methylation information through sequencing. We will do the "site" selection based on information we already know about where DNA methylation changes are important, for example, at genes and their regulatory sites, and using data from a set of animals that have DNA methylation data obtained through sequencing. At the moment, cattle is the livestock species with the most DNA methylation information derived from sequencing. So we will initially focus on cattle to design an array that will facilitate affordable epigenetic research in that species using our computational workflow, that can then be used in other species as the amount of data increases. We will work with a company that can produce the first DNA methylation kits designed to cover the most informative parts of the genome with respect to trait variation. This work could potentially have a major economic impact as it could contribute to the breeding of healthier and more efficient livestock, which could decrease the environmental impact of animal production, through, for example, better use of resources or lower methane emissions.

表观遗传标记是基因组上不涉及DNA序列改变的变化。通常研究的表观遗传标记是DNA甲基化，它影响基因的表达方式，并与人类和动物的疾病和其他特征有关。DNA甲基化可以决定一个特定的基因是否在一个特定的组织中被打开（表达）。研究表明，与DNA序列不同，DNA甲基化也可以作为我们所处环境的记录。例如，一些DNA甲基化“位点”可以区分吸烟者和不吸烟者，不同营养状态或生育能力的动物。目前，研究DNA甲基化只能通过使用昂贵的测序技术来实现，而这种过高的成本阻碍了科学家研究牲畜的DNA甲基化，以及它如何有助于为选择策略提供信息，从而有效和可持续地培育健康和多产的动物。我们提出的项目将开发工具，使这些研究成为可能。我们与家畜表观遗传学领域的领导者、工业合作伙伴和育种者合作，形成了一个真正具有共同目标的多学科团队。由于存在多种牲畜物种，我们建议开发计算工具，以选择最具信息量的DNA甲基化“位点”，并在类似于直接面向消费者的基因检测试剂盒的表观遗传试剂盒中进行测试。这种使用DNA甲基化阵列（试剂盒）完成的表观遗传学测试，比通过测序获得DNA甲基化信息要便宜得多。我们将根据我们已经知道的DNA甲基化变化在哪里重要的信息进行“位点”选择，例如，在基因及其调控位点，并使用一组通过测序获得DNA甲基化数据的动物的数据。目前，牛是从测序中获得最多DNA甲基化信息的牲畜物种。因此，我们首先将重点放在牛身上，设计一个阵列，利用我们的计算工作流程，促进对该物种进行可负担得起的表观遗传研究，然后随着数据量的增加，可以用于其他物种。我们将与一家能够生产首个DNA甲基化试剂盒的公司合作，该试剂盒旨在覆盖基因组中与性状变异相关的最具信息性的部分。这项工作可能会产生重大的经济影响，因为它可能有助于培育更健康、更高效的牲畜，从而可以通过更好地利用资源或减少甲烷排放等方式减少动物生产对环境的影响。