DNA POLYMORPHISM ANALYSIS OF CF IN A UNIQUE POPULATION

本项目是对与遗传缺陷相关的DNA多态性的研究 囊性纤维化（CF）和他们的分离，在一个高度近交 人口 该项目的长期目标是确定基因 与基本遗传缺陷特别相关的序列， CF，并最终鉴定和表征CF基因。 基因 最初鉴定的序列可以代表实际改变的（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 通过限制性片段长度多态性连锁分析鉴定 主要是在包含多个CF受影响个体的大型亲属中。 这种近亲是一个定义明确的近亲繁殖群体的一部分，即俄亥俄州旧秩序 阿米什人 搜索链接序列必须有一个任意的开始， 没有CF基因的染色体分配。 第一批探测器 与CF连锁的测试已经定位于6号染色体和 11号染色体短臂。 这些染色体含有丰富的DNA， 蛋白质标记聚集成连锁群，这将允许快速 CF连锁或排除图构建的进展。 一 将为9号染色体构建流式分选文库。 克隆探针 从这个文库中将一个亚区分配给一个9使用突变细胞 线 这些探针将用于信息分析中的连锁分析。 CF家族 这项研究的另一个目标是描述一个 近亲繁殖和中性DNA漂移的关系，通过研究 DNA多态性在近交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.