Esterling L E, Cox Matise T, Sanders A R, Yoshikawa T, Overhauser J, Gershon E S, Moskowitz M T, Detera-Wadleigh S D
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
Mol Psychiatry. 1997 Oct-Nov;2(6):501-4. doi: 10.1038/sj.mp.4000317.
The reported linkage between bipolar disorder and a large pericentric portion of chromosome 18 has been replicated in an independent study. Further examination of this region showed that 18p11.2 had the greatest allele sharing in our pedigrees and increased sharing in other independently ascertained pedigree series permitting refinement of the region of significance. To facilitate positional cloning of a susceptibility gene, we used a combination of mapping reagents, including a subchromosomal somatic cell hybrid panel, a contig of clones in yeast artificial chromosomes (YAC), and a radiation hybrid (RH) panel, to construct a high resolution physical map of the region including sequence tag sites (STSs) and expressed sequence tags (ESTs). This approach generated the interlocus distance and order of 15 STSs and 16 ESTs including four novel transcripts, with an average of approximately 200 kb between loci, over a approximately 6-Mb region. This high resolution integrated map will be an important tool in providing loci for contig construction, and positional candidates for mutation screening.
双相情感障碍与18号染色体大片段近着丝粒区域之间已报道的连锁关系在一项独立研究中得到了验证。对该区域的进一步研究表明，18p11.2在我们的家系中具有最大的等位基因共享性，并且在其他独立确定的家系系列中共享性增加，从而使得显著区域得以细化。为了便于对易感基因进行定位克隆，我们使用了多种定位试剂，包括一个亚染色体体细胞杂交板、酵母人工染色体（YAC）中的一组克隆重叠群以及一个辐射杂交（RH）板，来构建该区域的高分辨率物理图谱，其中包括序列标签位点（STS）和表达序列标签（EST）。这种方法确定了15个STS和16个EST（包括4个新转录本）的基因座间距离和顺序，在大约6兆碱基的区域内，基因座之间平均间距约为200千碱基。这一高分辨率整合图谱将成为构建重叠群的基因座定位以及突变筛查的位置候选基因的重要工具。
