Tomlinson I P, Neale K, Talbot I C, Spigelman A D, Williams C B, Phillips R K, Bodmer W F
Cancer Genetics Laboratory, Imperial Cancer Research Fund, London, UK.
J Med Genet. 1996 Apr;33(4):268-73. doi: 10.1136/jmg.33.4.268.
Mutations of the APC gene cause familial adenomatous polyposis (FAP) in humans and multiple intestinal neoplasia (Min) in laboratory mouse strains. A dominant modifying gene (Mom1), which partially suppresses the min phenotype, has been mapped to mouse chromosome 4. This region is syntenic with human chromosome 1p35-p36. The phospholipase A2 (Pla2s) locus is an excellent candidate for Mom1 and the equivalent human locus PLA2G2A is found on chromosome 1p35. It does not necessarily follow, however, than any modifier of mouse polyposis also influences human disease. In order to test whether a locus on 1p modifies FAP, subjects from 28 FAP families have been typed at microsatellite loci on this chromosome arm. The severity of their duodenal polyposis has also been assessed by endoscopy. Pedigree (lod score) linkage analysis found no evidence of a simple, dominant modifying gene, comparable with the action of Mom1 in inbred mouse strains. Given the more complex genetic and environmental interactions likely to exist in outbred human populations, it is probably more appropriate to use tests which do not specify a mode of inheritance. Using these methods of analysis, the data suggest that a locus on chromosome 1p35-p36 may influence the severity of duodenal FAP.
APC基因的突变会导致人类患家族性腺瘤性息肉病（FAP）以及实验小鼠品系患多发性肠道肿瘤（Min）。一种显性修饰基因（Mom1）已被定位于小鼠4号染色体，该基因可部分抑制Min表型。此区域与人类1号染色体p35 - p36区段同线。磷脂酶A2（Pla2s）基因座是Mom1的一个极佳候选基因，在人类中与之对应的基因座PLA2G2A位于1号染色体p35上。然而，小鼠息肉病的任何修饰基因不一定也会影响人类疾病。为了检测1p上的一个基因座是否修饰FAP，对28个FAP家族的受试者在该染色体臂的微卫星基因座上进行了分型。还通过内镜检查评估了他们十二指肠息肉病的严重程度。系谱（对数优势比分）连锁分析未发现存在与近交小鼠品系中Mom1作用类似的简单显性修饰基因的证据。考虑到远交人群中可能存在更复杂的遗传和环境相互作用，使用不指定遗传模式的检测方法可能更为合适。通过这些分析方法，数据表明1号染色体p35 - p36上的一个基因座可能影响十二指肠FAP的严重程度。
