Identifying factors required for genomic DNA methylation using the imprinting control protein ZFP57

我们每个人都从母亲那里继承了一份基因，从父亲那里继承了一份基因，通常只有当两份基因都被损坏时，我们才会患上遗传疾病。然而，我们大约1%的基因是印记的--尽管来自父母双方的基因具有相同的序列，但它们的控制方式不同，因此只能使用父母一方的拷贝。印记基因特别容易发生突变，因为它只有一个活跃的拷贝。如果它的序列或它的控制被破坏，那一个拷贝将无法工作，结果是印记紊乱。印记障碍通常在幼儿期出现-受影响的儿童可能非常大或小，或非常虚弱，或无法进食或茁壮成长，他们有学习或行为困难。医生们目前发现印记紊乱很难诊断，因为通常基因本身没有问题，只是它们的控制方式有问题。但是很多孩子都有类似的问题，这些问题发生在印记疾病中--生长、喂养和学习方面的问题--所以如果我们能找到更多关于印记的信息，我们也许就能诊断和帮助更多的孩子。我们最近发现，一种名为ZFP 57的基因突变会导致印记疾病。我们相信ZFP57与某些基因中的特殊DNA序列结合，并将它们标记出来。因此，我们希望利用ZFP 57作为杠杆来发现有关印迹的新事物。(A)我们将确切地找出ZFP 57结合的DNA序列，因为这将告诉我们什么DNA对印记很重要，以及它在印记疾病中是如何突变的。(B)我们将研究具有ZFP57突变和类似印记疾病的人的DNA，以确切地找出哪些印记基因受到影响，因为这将有助于我们识别影响生长和发育的新印记突变。（C）.我们将找出哪些因素与ZFP 57一起工作，以帮助它控制印记，因为这将告诉我们整个过程通常如何工作，以及它如何在疾病中出错。我们将与医生和NHS科学家密切合作，以便我们的研究结果可用于诊断，支持和治疗患有这些疾病的儿童。

We each inherit one copy of every gene from our mothers, and one copy from our fathers, and generally we only develop a genetic disease if both copies are damaged. However, about 1% of our genes are imprinted - though the genes from both parents have the same sequence, they are controlled differently, so that only one parent's copy can be used. An imprinted gene is in special danger of mutation, because it has only one active copy. If either its sequence or its control is disrupted, that one copy will not work, and the result is an imprinting disorder. Imprinting disorders often show themselves in early childhood - the affected children may be strikingly big or small, or very weak, or unable to feed or thrive, and they have learning or behavioural difficulties. Doctors currently find imprinting disorders hard to diagnose, because often there's nothing wrong with the genes themselves, just with the way they are controlled. But a lot of children have the same kind of problems that occur in imprinting disorders - problems with growth, feeding and learning - so if we can find out more about imprinting, we may be able to diagnose and help many more children.We recently found that mutation of a gene called ZFP57 causes imprinting disorders. We believe that ZFP57 binds to special sequences of DNA in some genes and marks them out to be imprinted. Therefore, we want to use ZFP57 as leverage to find out new things about imprinting. (A) We will find out exactly what DNA sequences ZFP57 binds to, because that will tell us just what DNA is important for imprinting and how it be mutated in imprinting disorders. (B) We will study the DNA of people with ZFP57 mutation and similar imprinting disorders, to find out exactly what imprinted genes are affected, because this will help us identify new imprinting mutations that affect growth and development. (C). We will find out what factors work with ZFP57 to help it control imprinting, because that will tell us about how the whole process normally works and how it can go wrong in disease. We will work closely with doctors and NHS scientists so that our findings can be used to diagnose, support and treat children with these disorders.