Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5.
Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5.
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家族性腺瘤性息肉病的遗传缺陷定位在 5 号染色体的小区域内。
DOI：
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发表时间：
1988
影响因子：
9.8
通讯作者：
Ray White
中科院分区：
文献类型：
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作者：
Yusuke Nakamura;Mark Lathrop;M. Leppert;Marc Dobbs;J. Wasmuth;Erica Wolff;M. Carlson;E. Fujimoto;K. Krapcho;Tena Sears;S. Woodward;J. Hughes;Randy;Burtj;Eldon Gardner;J. Lalouel;Ray White
家族性腺瘤性息肉病(FAP)是一种孟德尔疾病，包括家族性结肠息肉病(FPC)和Gardner综合征(GS)，具有常染色体显性遗传模式。它的特点是成百上千的腺瘤性息肉可以进展到结肠癌，这表明携带FAP胚系突变的基因可能在结肠癌的体细胞遗传途径中发挥重要作用。最近，通过FPC表型与DNA探针pC11p11(D5S71)所定义的位于5q21-22的一个基因座之间的连锁，导致FAP的缺陷被定位到5号染色体的长臂上。由于疾病基因鉴定的下一个重要步骤是获得更精确的定位，我们通过连锁分离和定位了FAP区域的另外6个多态DNA标记。随后对6个家系进行连锁分析，其中3个具有FPC表型，3个分离GS，将FAP基因座放置在一个新标记YN5.48(D5S81)附近，该标记在遗传图谱上约为C11p11远端17厘米器官。分析没有发现这两种表型之间存在遗传异质性的证据，这是早期研究没有明确解决的问题。FAP基因座附近的一组新的标志物代表着朝着隔离遗传缺陷又迈进了一步，并为分离腺瘤性息肉病家族中的个体进行结肠癌风险状态的临床前诊断提供了机会。
Familial adenomatous polyposis (FAP), a Mendelian disorder that includes familial polyposis coli (FPC) and Gardner syndrome (GS), has an autosomal dominant mode of inheritance. It is characterized by hundreds to thousands of adenomatous polyps that can progress to carcinoma of the colon, suggesting that the gene that harbors the FAP germ-line mutation may play an important role in the somatic genetic pathway to colon cancer. The defect responsible for FAP was recently mapped to the long arm of chromosome 5 by linkage between the FPC phenotype and a locus defined by DNA probe pC11p11 (D5S71), located at 5q21-22. Because an important next step in the paradigm for identification of a disease gene is to obtain a more precise localization, we isolated and mapped by linkage six additional polymorphic DNA markers in the FAP region. Subsequent linkage analysis in six pedigrees, three having the FPC phenotype and three segregating GS, placed the FAP locus very close to a new marker, YN5.48 (D5S81), that is approximately 17 centimorgans distal to C11p11 on the genetic map. The analysis revealed no evidence of genetic heterogeneity between the two phenotypes, a question that had not been clearly resolved by the earlier studies. The new set of markers in the near vicinity of the FAP locus represents a further step toward isolation of the genetic defect and provides the opportunity for preclinical diagnosis of risk status for colon cancer among individuals in families that are segregating adenomatous polyposis.
影响因子：
56.9
作者：
LEPPERT, M;DOBBS, M;WHITE, R
通讯作者：
WHITE, R
影响因子：
56.9
作者：
FEARON, ER;HAMILTON, SR;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B