Poduslo S E, Dean M, Kolch U, O'Brien S J
Program Resources, Incorporated/DynCorp, Frederick, MD.
Am J Hum Genet. 1991 Jul;49(1):106-11.
A strategy is described that allows the development of polymorphic genetic markers to be characterized in individual genes. Segments of the 3' untranslated regions are amplified, and polymorphisms are detected by digestion with frequently cutting enzymes and with the detection of single-stranded conformation polymorphisms. This allows these genes, or DNA segments, to be placed on the linkage maps of human chromosomes. Polymorphisms in two genes have been identified using this approach. A HaeIII polymorphism was detected in the KIT proto-oncogene, physically assigned to chromosome 4q11-12. This polymorphism is linked to other chromosome 4p markers and is in linkage disequilibrium with a HindIII polymorphism previously described at this locus. We have also identified in the insulin-like growth factor1 receptor gene (IGF1R) a 2-bp deletion that is present at a frequency of .25 in the Caucasian population. Pedigree analysis with this insertion/deletion polymorphism placed the IGF1R gene at the end of the current linkage map of chromosome 15q, consistent with the physical assignment of 15q2526. Thus, polymorphisms in specific genes can be used to related the physical, genetic, and comparative maps of mammalian genomes and to simplify the testing of candidate genes for human diseases.
本文描述了一种策略，该策略可用于开发在单个基因中进行特征鉴定的多态性遗传标记。对3'非翻译区的片段进行扩增，并通过用常用切割酶消化以及检测单链构象多态性来检测多态性。这使得这些基因或DNA片段能够定位到人类染色体的连锁图谱上。利用这种方法已鉴定出两个基因中的多态性。在原癌基因KIT中检测到一种HaeIII多态性，该基因在物理上定位于染色体4q11 - 12。这种多态性与其他4号染色体短臂标记连锁，并且与此前在该位点描述的一种HindIII多态性处于连锁不平衡状态。我们还在胰岛素样生长因子1受体基因（IGF1R）中鉴定出一个2碱基对的缺失，在白种人群体中的出现频率为0.25。利用这种插入/缺失多态性进行家系分析，将IGF1R基因定位在当前15号染色体q臂连锁图谱的末端，这与15q25 - 26的物理定位一致。因此，特定基因中的多态性可用于关联哺乳动物基因组的物理图谱、遗传图谱和比较图谱，并简化对人类疾病候选基因的检测。
