Guru S C, Olufemi S E, Manickam P, Cummings C, Gieser L M, Pike B L, Bittner M L, Jiang Y, Chinault A C, Nowak N J, Brzozowska A, Crabtree J S, Wang Y, Roe B A, Weisemann J M, Boguski M S, Agarwal S K, Burns A L, Spiegel A M, Marx S J, Flejter W L, de Jong P J, Collins F S, Chandrasekharappa S C
Laboratory of Gene Transfer, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA.
Genomics. 1997 Jun 15;42(3):436-45. doi: 10.1006/geno.1997.4783.
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疾病，会导致受影响个体发生甲状旁腺、垂体前叶以及胰腺和十二指肠内分泌肿瘤。MEN1基因座与位于11q13染色体上的PYGM标记紧密连锁，连锁分析将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YAC和细菌克隆（PAC、BAC和P1）组成，覆盖D11S480至D11S913区域。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）进行的高密度STS含量分析以及118个STS组装而成的。这些STS包括22个多态性标记和20个转录本，其余主要来自基因组克隆的末端序列。还生成了一个针对1兆碱基PYGM-SEA区域的独立黏粒重叠群。通过纤维荧光原位杂交对克隆进行独立排序，为2.8兆碱基重叠群图谱的正确性提供了支持。这个可用于测序的重叠群将成为定位克隆MEN1以及其他基因座位于该区域的疾病基因的有用资源。
