LINKAGE ANALYSIS OF CYSTIC FIBROSIS

该项目的目的是应用现有的检测方法， 多态性遗传标记与囊性纤维化的连锁分析 纤维化尤其是信息丰富的家庭。 该项目涉及一个 由L.O.指导的实验室之间的合作。卡瓦利-斯福尔扎和 玛丽-克莱尔·金为了找到和抽样足够的家庭， 调查足够数量的多态性DNA和蛋白质标记。 的 该项目的具体目标是：（1）特别挑选家庭， 为囊性纤维化的连锁研究提供信息;（2）筛选所有 可用的多态性DNA和蛋白质标记，目的是定位 囊性纤维化基因（CF）在标记物的合理小距离内 基因座;（3）如果成功，寻找新的多态性标记 更接近CF。 通过应用现有技术在DNA水平上检测多态性， 到囊性纤维化的遗传分析，现在原则上， 来精确定位cf在人类基因组上的位置。 然而，大量的 获得足够的连锁信息所需的标记和家庭 蛋白质产物未知的隐性疾病基因的分析将 似乎使这种努力不切实际。 为了进行连锁分析 囊性纤维化的可行性，该项目将利用两个技巧， 抽样设计和实验室技术。 首先，研究样本将 包括至少有两名受影响儿童的家庭， 父母可用。 这类家庭的收入大约是 有一名受影响儿童和一名未受影响儿童的家庭的信息， 甚至比只有一个的大型兄弟姐妹提供更多的信息 受影响的孩子 第二，筛选可能与cf相关的DNA标记， 将采用多种探针和混合物， 可以同时分析。 这些功能将减少总 测试数量足以合理地建议定位cf 在相对较短的时间内以相当高的精度进行。 找到一个合理接近cf的遗传标记可以使产前 在高危家族中诊断囊性纤维化和检测 这些家庭中的携带者。

The purpose of this project is to apply current methods for detection and analysis of polymorphic genetic markers to linkage analysis of cystic fibrosis in especially informative families. The project involves a collaboration between the laboratories directed by L.O. Cavalli-Sforza and Mary-Claire King in order to locate and sample sufficient families and survey an adequate number of polymorphic DNA and protein markers. The specific aims of the project are: (1) to select families especially informative for linkage studies of cystic fibrosis; (2) to screen all available polymorphic DNA and protein markers, with the aim of locating the cystic fibrosis gene (cf) within a reasonably small distance of a marker locus; and (3) if this is successful, to look for new polymorphic markers closer to cf. By applying present techniques for detecting polymorphisms at the DNA level to genetic analysis of cystic fibrosis, it is now possible, in principle, to precisely locate cf on the human genome. However, the very large number of markers and families required to obtain adequate information for linkage analysis of a recessive disease gene whose protein product is unknown would seem to make such an effort impractical. In order to make linkage analysis of cystic fibrosis feasible, this project will exploit two tricks of sampling design and laboratory technique. First, the study sample will include only families with at least two living, affected children and both parents available. Such families include about seven times as much information as families with one affected and one unaffected child and considerably more information than even very large sibships with only one affected child. Second, screening for DNA markers potentially linked to cf will employ multiple probes and mixtures so that up to ten polymorphisms can be analyzed simultaneously. These features will reduce the total number of tests sufficiently that it is reasonable to propose locating cf with considerable precision in a relatively short time. Finding a genetic marker reasonably close to cf could enable prenatal diagnosis of cystic fibrosis in families at high risk and detection of carriers in such families.