A 2.8-Mb clone contig of the multiple endocrine neoplasia type 1 (MEN1) region at 11q13.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder that results in parathyroid, anterior pituitary, and pancreatic and duodenal endocrine tumors in affected individuals. The MEN1 locus is tightly linked to the marker PYGM on chromosome 11q13, and linkage analysis has placed the MEN1 gene within a 2-Mb interval flanked by D11S1883 and D11S449. As a step toward cloning the MEN1 gene, we have constructed a 2.8-Mb clone contig consisting of YAC and bacterial clones (PAC, BAC, and P1) for the D11S480 to D11S913 region. The bacterial clones alone represent nearly all of the 2.8-Mb contig. The contig was assembled based on a high-density STS-content analysis of 79 genomic clones (YAC, PAC, BAC, and P1) with 118 STSs. The STSs included 22 polymorphic markers and 20 transcripts, with the remainder primarily derived from the end sequences of the genomic clones. An independent cosmid contig for the 1-Mb PYGM-SEA region was also generated. Support for correctness of the 2.8-Mb contig map comes from an independent ordering of the clones by fiber-FISH. This sequence-ready contig will be a useful resource for positional cloning of MEN1 and other disease genes whose loci fall within this region.

1型多发性内分泌腺瘤病（MEN1）是一种常染色体显性遗传病，可导致受累个体出现甲状旁腺、垂体前叶以及胰腺和十二指肠内分泌肿瘤。MEN1基因座与11号染色体q13区的PYGM标记紧密连锁，连锁分析已将MEN1基因定位在D11S1883和D11S449两侧的2兆碱基区间内。作为克隆MEN1基因的一个步骤，我们构建了一个2.8兆碱基的克隆重叠群，它由针对D11S480到D11S913区域的酵母人工染色体（YAC）和细菌克隆（P1人工染色体、细菌人工染色体和P1噬菌体）组成。仅细菌克隆就几乎代表了整个2.8兆碱基的重叠群。该重叠群是基于对79个基因组克隆（YAC、PAC、BAC和P1）使用118个序列标签位点（STS）进行的高密度STS含量分析而组装的。这些STS包括22个多态性标记和20个转录本，其余的主要来自基因组克隆的末端序列。还构建了针对1兆碱基PYGM - SEA区域的独立粘粒重叠群。对2.8兆碱基重叠群图谱正确性的支持来自纤维荧光原位杂交（fiber - FISH）对克隆的独立排序。这个可用于测序的重叠群将是对MEN1以及其他位于该区域的疾病基因进行定位克隆的有用资源。