MOLECULAR ANALYSIS OF THE CYSTIC FIBROSIS GENE

囊性纤维化(CF)是由囊性纤维化突变引起的 跨膜电导调节因子(CFTR)基因。500多种不同的 已在CFTR基因中发现突变。然而，严重程度 CF患者肺部疾病的发生率是高度可变的，即使在 具有相同基因型别的个体。这一数据表明，有 其他遗传和/或环境因素导致 慢性阻塞性肺疾病的严重程度。它还表明，严重的 肺病的发病率在CF兄弟姐妹中显著一致， 这表明存在一个主要的遗传因素。此外，分析 对cftr基因缺陷小鼠遗传背景影响的研究表明 其他基因对疾病的严重程度起着重要作用。其目的是 本项目的主要目的是确定异质性的遗传基础。 Cf患者。我们已经从几个CF患者队列中获得了DNA 并将这些患者归类为患有轻度或重度肺部疾病 关于他们的年龄和肺功能。我们已经分析了这些患者群体 寻找与参与免疫的基因的遗传标记的关联 回应。轻度疾病的患者有更高的频率 HLADQA101等位基因和301等位基因频率降低。这 提示人类白细胞抗原基因座可能与肺的严重程度有关。 慢性阻塞性肺病患者的疾病。

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Over 500 different mutations have been identified in the CFTR gene. However, the severity of pulmonary disease in CF patients is highly variable, even in individuals with the same genotype. This data suggests that there are additional genetic and/or environmental factors that contribute to the severity of CF lung disease. It has also been shown that the severity of lung disease is significantly concordant amongst CF siblings, suggesting that a major genetic factor is present. Furthermore, analysis of the effect of genetic background in CFTR-deficient mice indicates that other genes play an important role in the severity of disease. The aim of this project is to identify the genetic basis of the heterogeneity in CF patients. We have obtained DNA from several cohorts of CF patients and classified these patients as having mild or severe lung disease based on their age and lung function. We have analyzed these patient groups for associations with genetic markers for genes involved in the immune response. Patients with mild disease have an increased frequency of the HLA DQA 101 allele and a decreased frequency of the 301 allele. This suggests that the HLA locus may contribute to the severity of lung disease in CF patients.