Sequence variation and DNA methylation patterning

DNA可以通过添加或删除小的化学标签来修改，这可能会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上化学标签的添加和删除被认为是造成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能具有完全不同的身份(例如，心脏细胞和血细胞)。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上的。是什么因素导致了这些标签的增加？在什么时候，它们被添加或从DNA中移除，才能影响细胞命运的决定？这些化学标签的维护是否需要蜂窝架构？鉴于有许多因素可以影响将这些化学标签添加到DNA中，当前的研究计划将调查其中一个因素，即DNA区域的两侧，如何影响这些化学标签。具体地说，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，我们将选择在众所周知的DNA化学标签(称为甲基团)位置附近的常见DNA序列变异的位置。我们将研究在每个位置有DNA改变的人和在这些位置没有DNA改变的人，并评估这些健康个体的DNA局部甲基化模式。我们假设DNA序列变异将影响这些局部区域化学标签的图案。

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.