通过连锁分析将2A型多发性内分泌腺瘤定位到10号染色体。

Assignment of multiple endocrine neoplasia type 2A to chromosome 10 by linkage.

作者信息

Simpson N E, Kidd K K, Goodfellow P J, McDermid H, Myers S, Kidd J R, Jackson C E, Duncan A M, Farrer L A, Brasch K

出版信息

Nature. 1987;328(6130):528-30. doi: 10.1038/328528a0.

Abstract

Multiple endocrine neoplasis type 2A (MEN2A) is one of several kinds of cancers that appear to be inherited in an autosomally dominant fashion. We have assigned the MEN2A locus to chromosome 10 by linkage with a new DNA marker (D10S5). The linkage led us to investigate other chromosome 10 markers and demonstrate linkage between the disease locus and the interstitial retinol-binding protein (IRBP) gene. The D10S5 locus was sublocalized to 10q21.1 by hybridization in situ and the IRBP gene to p11.2----q11.2 with a secondary site at q24----q25. The linkages were established using 292 members of five families, three different restriction fragment length polymorphisms (RFLPs) at D10S5 and two RFLPs recognized by the IRBP probe. The recombination frequencies from pairwise linkage analysis between the disease and two marker loci D10S5 and IRBP were 0.19 and 0.11, with maximum lod scores of 3.6 and 8.0 respectively. Ordering of the three loci by multipoint analysis placed the IRBP gene approximately midway between the disease and D10S5 loci.

摘要

2A型多发性内分泌肿瘤（MEN2A）是几种似乎以常染色体显性方式遗传的癌症之一。我们通过与一种新的DNA标记（D10S5）连锁分析，将MEN2A基因座定位于10号染色体。这种连锁关系促使我们研究10号染色体上的其他标记，并证明疾病基因座与间质视黄醇结合蛋白（IRBP）基因之间存在连锁关系。通过原位杂交将D10S5基因座定位到10q21.1，将IRBP基因定位到p11.2----q11.2，在q24----q25处有一个次要位点。利用五个家族的292名成员、D10S5处的三种不同限制性片段长度多态性（RFLP）以及IRBP探针识别的两种RFLP建立了连锁关系。疾病与两个标记基因座D10S5和IRBP之间的成对连锁分析的重组频率分别为0.19和0.11，最大lod值分别为3.6和8.0。通过多点分析对三个基因座进行排序，结果显示IRBP基因大致位于疾病基因座和D10S5基因座之间。