Sequence variation and DNA methylation patterning

序列变异和 DNA 甲基化模式

• 批准号: 435512-2013
• 负责人: Ernst, Carl
• 金额: $ 2.33万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=650270
• 关键词: Sequence; variation; DNA; methylation; patterning

DNA can be modified by the addition or removal of small chemical tags which can have profound repercussions on the organism; why is a skin cell a skin cell and not a brain cell? Why is a blood cell a blood cell and not a heart cell? The addition and removal of chemical tags to DNA is thought to be responsible for these different cell fates, which explains why cells with identical genomes can have completely different identities (eg heart cell vs a blood cell). The long term objectives of this research program are to understand how and why this particular chemical tag gets added to DNA. What factors contribute to the addition of these tags? At what point are they added or removed from DNA to influence cell fate decisions? Is there cellular architecture required for the maintenance of these chemical tags? Given that there are a number of factors that can influence the addition of these chemical tags to DNA, the current research program will investigate how one of these factors, flanking DNA regions, influence these chemical tags. Specifically, it will address the relationship between, normal non-pathogenic deletions in the genome to theses chemical tags. To do this, we will select sites of common DNA sequence variation that are near well known sites of DNA chemical tags (called methyl groups). We will study people with DNA alterations at each of these sites and people without DNA alterations at these sites, and assess the local methylation pattern of the DNA in these healthy individuals. We hypothesize that DNA sequence variation will influence the patterning of the chemical tags in these local regions. ********************

DNA可以通过添加或去除小的化学标签进行修改，这可能对生物体产生深远的影响;为什么皮肤细胞是皮肤细胞而不是脑细胞？ 为什么血细胞是血细胞而不是心脏细胞？ DNA中化学标签的添加和去除被认为是导致这些不同细胞命运的原因，这解释了为什么具有相同基因组的细胞可以具有完全不同的身份（例如心脏细胞与血细胞）。 这项研究计划的长期目标是了解这种特殊的化学标签是如何以及为什么被添加到DNA中的。 是什么因素促成了这些标签的添加？ 在什么时候它们被添加或从DNA中移除以影响细胞命运的决定？ 这些化学标记的维持需要细胞结构吗？ 鉴于有许多因素可以影响这些化学标签添加到DNA中，目前的研究计划将研究这些因素之一，侧翼DNA区域如何影响这些化学标签。 具体来说，它将解决基因组中正常的非致病性缺失与这些化学标签之间的关系。为此，我们将选择常见DNA序列变异的位点，这些位点靠近众所周知的DNA化学标签（称为甲基）位点。 我们将研究在这些位点上有DNA改变的人和在这些位点上没有DNA改变的人，并评估这些健康个体中DNA的局部甲基化模式。 我们假设DNA序列变异会影响这些局部区域中化学标签的模式。********************