Sequence variation and DNA methylation patterning

DNA可以通过添加或去除小的化学标签来修饰，这些标签可以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？为什么血液细胞是血液细胞而不是心脏细胞？DNA化学标签的添加和移除被认为是导致这些不同细胞命运的原因，这就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（例如心脏细胞和血细胞）。这个研究项目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上的。是什么因素导致了这些标签的增加？它们在什么时候从DNA中加入或移除来影响细胞命运的决定？这些化学标签的维护是否需要细胞结构？鉴于有许多因素可以影响这些化学标签添加到DNA上，当前的研究计划将调查这些因素之一，DNA区域的侧翼，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，我们将选择常见的DNA序列变异位点，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序列的变化将影响这些局部区域的化学标签的模式。

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.