MUTATIONAL ANALYSIS OF THE CYSTIC FIBROSIS GENE

囊性纤维化是最常见的致死性遗传病，影响 高加索人。这种疾病是由囊性癌基因突变引起的。 纤维化跨膜传导调节因子(CFTR)基因。CFTR编码 一种属于膜运输分子超家族的蛋白质 结合三磷酸腺苷，并将特定的分子泵出细胞。超过250个 CFTR基因中的不同突变已经被表征，这些 在大多数人群中，突变占疾病等位基因的80%-90%。 CF患者肺部疾病的严重程度具有高度的异质性。 即使在具有相同基因的个体中，也存在广泛的差异。 在疾病的发展过程中，表明额外的基因 和/或环境因素起作用。先前的研究表明， CF兄弟姐妹之间的病程显著一致， 这表明存在一个主要的遗传因素。这件事的重点是 该项目是为了确定林木异质性的遗传基础。 病人。我们分析了一组患有轻度肺纤维化的患者。 疾病与相关基因的遗传标记有关 免疫反应。将这些患者与一组患有 严重的疾病。我们观察到人类白细胞抗原DQA 101与 等位基因和轻度疾病。此外，我们还观察到一种关联 白细胞介素1抑制物中的一个等位基因与慢性阻塞性肺疾病 严肃性。在每一个案例中，我们都在收集关于 更多的患者试图确认这些关联。

Cystic fibrosis (CF) is the most common fatal genetic disease affecting Caucasian populations. The disease is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR encodes a protein that is part of a superfamily of membrane transport molecules that bind ATP and pump specific molecules out of the cell. More than 250 different mutations have been characterized in the CFTR gene, and these mutations account for 80-90% of the disease alleles in most populations. The severity of pulmonary disease in CF patients is highly heterogeneous. Even in individuals with the same genotype there is extensive variation in the progression of the disease, suggesting that additional genetic and/or environmental factors contribute. Previous work has shown that the course of disease is significantly concordant amongst CF siblings, suggesting that a major genetic factor is present. The focus of this project is to identify the genetic basis of the heterogeneity in CF patients. We have analyzed a cohort of CF patients with mild lung disease for associations with genetic markers for genes involved in the immune response. These patients are compared to a group of patients with severe disease. We have observed an association between the HLA DQA 101 allele and mild disease. In addition, we have observed an association between an allele in the interleukin-1 inhibitor and CF pulmonary disease severity. In each of these cases we are collecting information on additional patients to attempt to confirm these associations.