Olavesen M G, Davies A F, Broxholme S J, Wixon J L, Senger G, Nizetic D, Campbell R D, Ragoussis J
Division of Medical and Molecular Genetics, United Medical School of Guy's and St. Thomas's Hospital (UMDS), London, UK.
Genome Res. 1995 Nov;5(4):342-58. doi: 10.1101/gr.5.4.342.
The human chromosomal band 6p23 is a Giemsa-negative (light) band that may be expected to be relatively gene rich. The genes for spinocerebellar ataxia type 1 (SCA1), guanosine monophosphate reductase (GMPR), DEK involved in a subtype of acute myeloid leukemia (AML), and the folate-sensitive fragile site FRA6A, have already been mapped to 6p23. Recent linkage data have suggested evidence for a susceptibility locus for schizophrenia in the region. We have constructed a single YAC contig of approximately 100 clones spanning the entire 6p23 band from 6p22.3 to 6p24.1 and covering 7.5-8.5 Mb of DNA. The YAC contig contains 55 markers including genetically mapped STSs, physically mapped STSs, anonymous STSs, anonymous ESTs, and ESTs from the genes mapped to the region. The order of the genetically mapped STSs is consistent with their order in the contig and some of the markers not resolved on the genetic map have been resolved by the YACs. Four of the YACs from 6p23 and covering approximately 3 Mb of DNA have been used to isolate approximately 300 cosmids from a flow-sorted human chromosome 6 cosmid library, which have been organized into pockets. The proposed susceptibility locus for schizophrenia is most closely linked to D6S260, which is located within the YAC contig along with genetic markers < or = 5 cM on either side. Therefore, the presented materials are valuable reagents for characterization of the genomic region implicated in schizophrenia.
人类染色体带6p23是一条吉姆萨阴性(浅染)带,预计其基因相对丰富。1型脊髓小脑共济失调(SCA1)、鸟苷单磷酸还原酶(GMPR)、参与急性髓系白血病(AML)一种亚型的DEK以及叶酸敏感脆性位点FRA6A的基因,已被定位到6p23。最近的连锁数据表明该区域存在精神分裂症易感基因座的证据。我们构建了一个由大约100个克隆组成的单一酵母人工染色体(YAC)重叠群,覆盖从6p22.3到6p24.1的整个6p23带,包含7.5 - 8.5兆碱基对(Mb)的DNA。该YAC重叠群包含55个标记,包括遗传定位的序列标签位点(STSs)、物理定位的STSs、匿名STSs、匿名表达序列标签(ESTs)以及定位到该区域的基因的ESTs。遗传定位的STSs的顺序与它们在重叠群中的顺序一致,并且一些在遗传图谱上未解析的标记已通过YACs得到解析。来自6p23且覆盖约3 Mb DNA的4个YAC已用于从流式分选的人类6号染色体黏粒文库中分离出约300个黏粒,并将它们整理成文库。提议的精神分裂症易感基因座与D6S260紧密连锁,D6S260位于YAC重叠群内,其两侧还有遗传距离≤5厘摩(cM)的遗传标记。因此,所呈现的材料是用于表征与精神分裂症相关的基因组区域的有价值试剂。