Ferns G A, Hitman G A, Trembath R, Williams L, Tarn A, Gale E A, Galton D J
J Med Genet. 1986 Jun;23(3):210-6. doi: 10.1136/jmg.23.3.210.
The linked polymorphic loci 5' to the insulin gene and 3' to the c-Harvey-ras-1 (c-Ha-ras) gene, both localised to the short arm of chromosome 11, have been studied in 14 type I diabetic pedigrees. The use of a cloned gene probe corresponding to the polymorphic locus adjacent to the insulin gene, in combination with the restriction endonuclease PvuII, has permitted an improvement in the resolution of sizes of insert at this locus. An MspI restriction fragment length polymorphism at the c-Ha-ras proto-oncogene locus (4 cM upstream from the insulin gene) was used to identify parental insulin gene related alleles unambiguously, and subsequently a pedigree analysis was performed to determine whether subclasses of inserts at this locus track with insulin dependent diabetes. Segregation analysis demonstrated no linkage between the polymorphic loci 5' to the insulin gene, nor 3' to the c-Ha-ras, and type I diabetes. However, a similar analysis confirmed an association between the HLA locus chromosome 6 and insulin dependent diabetes.
已对14个I型糖尿病家系中位于胰岛素基因5'端和c-Harvey-ras-1（c-Ha-ras）基因3'端的连锁多态性位点进行了研究，这两个位点均位于11号染色体短臂上。使用与胰岛素基因相邻的多态性位点对应的克隆基因探针，结合限制性内切酶PvuII，提高了该位点插入片段大小的分辨率。c-Ha-ras原癌基因位点（胰岛素基因上游4 cM）的MspI限制性片段长度多态性被用于明确鉴定与亲本胰岛素基因相关的等位基因，随后进行家系分析以确定该位点的插入片段亚类是否与胰岛素依赖型糖尿病相关。分离分析表明，胰岛素基因5'端的多态性位点以及c-Ha-ras基因3'端的多态性位点与I型糖尿病之间均无连锁关系。然而，类似的分析证实了6号染色体上的HLA位点与胰岛素依赖型糖尿病之间存在关联。
