Functional and genetic analysis of PHF11, a new gene associated with atopic dermatitis and asthma

特应性皮炎或湿疹是一种越来越常见的严重过敏性皮肤病，影响着多达30%的澳大利亚儿童的皮肤。湿疹对家庭以及受影响儿童的健康和福祉都有重大的经济影响。大多数哮喘患者也会过敏，这就解释了为什么许多患有湿疹的儿童往往也会患上哮喘。哮喘或湿疹的家族史是孩子患上这种疾病的重要风险因素，这意味着过敏在很大程度上是由我们从父母那里遗传的基因决定的。我们的基因由四种不同的积木组成，称为核苷酸，由A、G、C和t四个字母识别，每个基因都有这四个字母的特定拼写，尽管在任何两个人之间，一个基因的拼写方式总会有单个字母的小差异。通常情况下，这些差异没有影响。然而，在过敏个体中，这些差异确实有影响。确定基因拼写方式的差异以及为什么会导致湿疹或哮喘是一个主要的研究目标。在过去的几年里，已经确定了许多基因在过敏中起着重要作用，我们最近发现了一个新基因的拼写差异，我们认为这对湿疹和哮喘的过敏反应很重要。目前，我们只能猜测这个基因是如何工作的。我们知道它是在免疫系统的细胞中表达的，在过敏中很重要。我们还怀疑它可能是其他对过敏很重要的基因的开关。这个项目将测试这些想法，并展示该基因拼写方式的差异如何导致该基因工作方式的差异。这对于解开基因如何控制过敏这一谜题来说是非常重要的，并且可能导致更好、更早地治疗这些疾病，改善受影响儿童和成人的健康状况。

Atopic dermatitis, or eczema, is an increasingly common severe allergic condition affecting the skin that afflicts up to 30% of all Australian children. Eczema has significant financial impact on families as well on the health and well being of the affected child. The majority of asthmatics are also allergic, explaining why many children who suffer from eczema often go on to develop asthma as well. A familial history of asthma or eczema is an important risk factors for a child developing the disorder, meaning that allergy is to a large extent determined by the genes we inherit from our parents. Our genes consist of four different building blocks, called nucleotides, which are identified by four letters: A, G, C and T. Each gene has a specific spelling of these four letters, although between any two people there will invariably be small single letter differences in the way a gene is spelt. Normally, these differences have no effect. In an allergic individual, however, these differences do have an effect. Identifying differences in the way a gene is spelt and why this should lead to eczema or asthma is a major research goal. In the past several years a number of genes have been identified that play an important role in allergy and we have recently identified a spelling difference in a new gene that we believe is important in the allergic response of eczema and asthma. At the moment, we can only guess how this gene might work. We know it is expressed in cells of our immune system that are important in allergy. We also suspect it might be an on or off switch for other genes important for allergy. This project will test these ideas and show how differences in the way this gene is spelt lead to differences in how this gene works. This will be important in adding another piece to the puzzle of how genes control allergy and could lead to better and earlier treatment of these disorders with improved health for affected children as well as adults.