Manenti G, Stafford A, De Gregorio L, Gariboldi M, Falvella F S, Avner P, Dragani T A
Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
Genome Res. 1999 Jul;9(7):639-46.
By using linkage disequilibrium (LD) analysis in 21 strains of known susceptibility to lung cancer and by assembling a YAC contig, we mapped to a approximately 1.5-Mb region on distal mouse chromosome 6 the Pas1 locus, the major determinant of lung cancer predisposition in mice. Our results, on the basis of haplotype and phenetic analysis, suggest that the Pas1(s) susceptibility allele is shared by several mouse-inbred strains of independent origin, which show either high or intermediate predisposition to lung tumorigenesis. Therefore, the Pas1(s) allele is probably derived from an ancestral mouse rather than from independent mutations of the same gene. We showed the feasibility of LD in common inbred strains for the fine mapping of disease loci, and provided the biological basis and the reagents for the cloning of the Pas1 gene.
通过对21株已知肺癌易感性的品系进行连锁不平衡（LD）分析，并构建一个酵母人工染色体（YAC）重叠群，我们将小鼠肺癌易感性的主要决定因素Pas1基因座定位到了小鼠6号染色体远端大约1.5兆碱基（Mb）的区域。基于单倍型和聚类分析的结果表明，几个独立起源的小鼠近交系共享Pas1（s）易感性等位基因，这些品系对肺癌发生表现出高易感性或中度易感性。因此，Pas1（s）等位基因可能源自一个祖先小鼠，而非同一基因的独立突变。我们展示了在常见近交系中利用LD进行疾病基因座精细定位的可行性，并为Pas1基因的克隆提供了生物学基础和试剂。
