MOLECULAR ANALYSIS OF THE CYSTIC FIBROSIS GENE

囊性纤维化（CF）是由囊性纤维化基因突变引起的。 跨膜传导调节因子（CFTR）基因。 超过500种不同的 突变已在CFTR基因中鉴定。 然而，严重性 CF患者肺部疾病的发生率差异很大，即使在 具有相同基因型的个体。 这些数据表明， 其他遗传和/或环境因素，有助于 CF肺病的严重程度。 它还表明，严重性 肺疾病的发病率在CF兄弟姐妹中显著一致， 这表明存在主要的遗传因素。 此外，分析 遗传背景对CFTR缺陷小鼠的影响表明， 其他基因在疾病的严重程度中起重要作用。 目的 该项目的目的是确定遗传基础的异质性， CF患者 我们从几组CF患者中获得了DNA， 并将这些患者分为轻度或重度肺部疾病， 对他们的年龄和肺功能的影响 我们分析了这些患者群体 与免疫相关基因的遗传标记的关联 反应 轻度疾病的患者， HLA-DQA 101等位基因和301等位基因频率降低。 这 提示HLA位点可能与肺结核的严重程度有关， CF患者的病情。

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.