Spirio L, Nelson L, Ward K, Burt R, White R, Leppert M
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City 84112.
Am J Hum Genet. 1993 Feb;52(2):286-96.
Presymptomatic genetic testing for the presence of a mutant allele causing familial adenomatous polyposis coli (APC) has been difficult to perform effectively in the past because DNA markers surrounding the APC gene on chromosome 5q have not been very informative. We report results of genetic linkage studies on both research families and clinical families by using D5S346, a highly polymorphic dinucleotide (CA)-repeat locus 30-70 kb from the APC gene. Linkage analysis with this marker in a large APC pedigree showed an increase of at least 9.0 LOD units, in likelihood of linkage of the disease-causing allele to the APC locus, when compared with the highest LOD score attained with any other closely linked marker. When the first 14 APC families that requested genotypic analysis by the DNA Diagnostic Laboratory at the University of Utah were tested with D5S346, 20 of the 31 at-risk individuals were identified as either carriers or noncarriers of an APC-predisposing allele. We see this marker as an important tool for research studies and for the presymptomatic diagnosis of APC.
过去，由于5号染色体上围绕腺瘤性结肠息肉病（APC）基因的DNA标记提供的信息不足，对导致家族性腺瘤性息肉病的突变等位基因进行症状前基因检测一直难以有效开展。我们报告了利用D5S346对研究家族和临床家族进行基因连锁研究的结果，D5S346是一个高度多态的二核苷酸（CA）重复位点，距离APC基因30 - 70 kb。在一个大型APC家系中，用该标记进行连锁分析显示，与任何其他紧密连锁标记所获得的最高LOD分数相比，致病等位基因与APC位点的连锁可能性增加了至少9.0个LOD单位。当犹他大学DNA诊断实验室对最初要求进行基因分型分析的14个APC家族用D5S346进行检测时，31名高危个体中有20人被确定为APC易感等位基因的携带者或非携带者。我们认为这个标记是研究和APC症状前诊断的重要工具。
