DNA POLYMORPHISM ANALYSIS OF CF IN A UNIQUE POPULATION

这个项目是对与遗传缺陷相关的DNA多态的研究。 囊性纤维化及其在高度近交系中的分离 人口。这个项目的长期目标是识别基因 与基本遗传缺陷相关的序列 Cf，并最终鉴定和鉴定cf基因。基因 最初识别的序列可能代表实际改变的(即 Cf)基因，但更有可能是连锁的DNA序列(标记 序列)。与Cf表型分离的基因序列将是 限制性片段长度多态的连锁分析鉴定 主要是在包含多个受CF影响的个体的大家族中。 亲属是定义明确的近亲繁殖群体--俄亥俄州旧秩序的一部分 阿米什人。搜索链接序列必须以任意开头 缺乏对Cf基因的染色体分配。第一批探测器 被测试与Cf连锁的基因被定位在6号染色体和 11号染色体的短臂。这些染色体具有丰富的DNA和 蛋白质标记聚集在连锁群中，这将允许快速 构建林木连锁或排除图谱的研究进展。一个 将构建9号染色体的流动排序文库。克隆的探针 从这个文库中将使用突变细胞分配到一个9的子区 台词。这些探针将用于信息性的连锁分析 Cf家庭。这项研究的另一个目标是描述一个 通过研究近亲交配与中性DNA漂移的关系 DNA多态在近交系群体中的分布和频率。

This project is a study of DNA polymorphisms related to the genetic defect of cystic fibrosis (CF) and their segregation in a highly inbred population. The long-term objective of this project is to identify gene sequences specifically related to the basic genetic defect responsible for CF, and ultimately to identify and characterize the CF gene. The gene sequences originally identified may represent the actual altered (i.e. "CF") gene, but are more likely to be linked DNA sequences (marker sequences). Gene sequences that segregate with the CF phenotype will be identified by linkage analysis of restriction fragment length polymorphisms primarily in a large kindred containing multiple CF affected individuals. The kindred is part of a well-defined inbred population, the Ohio Old Order Amish. The search for linked sequences must have an arbitrary beginning in the absence of a chromosomal assignment for the CF gene. The first probes tested for linkage to CF have been localized to chromosome 6 and to the short arm of chromosome 11. These chromosomes have abundant DNA and protein markers clustered into linkage groups, which will allow rapid progress in construction of linkage or exclusion maps for CF. A flow-sorted library will be constructed for chromosome 9. Cloned probes from this library will be assigned to a subregion of a 9 using mutant cell lines. These probes will be used for linkage analysis in the informative CF families. An additional goal of this research is to describe a relationship between inbreeding and neutral DNA drift, by studying the distribution and frequency of DNA polymorphisms in an inbred population.