Novel microsatellite markers and single nucleotide polymorphisms refine the tylosis with oesophageal cancer (TOC) minimal region on 17q25 to 42.5 kb:: sequencing does not identify the causative gene
Novel microsatellite markers and single nucleotide polymorphisms refine the tylosis with oesophageal cancer (TOC) minimal region on 17q25 to 42.5 kb:: sequencing does not identify the causative gene
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DOI：
10.1007/s00439-004-1100-3
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发表时间：
2004-05-01
期刊：
影响因子：
5.3
通讯作者：
Risk, JM
中科院分区：
文献类型：
--
作者：
Langan, JE;Cole, CG;Risk, JM
Tylosis（局灶性非表皮松解性掌跖角化症）与三个家族的鳞状细胞食管癌的早期发病有关。连锁和单倍型分析先前已将食管癌 (TOC) 基因座的类型定位到染色体 17q25 上的 500 kb 区域，该区域也与散发的鳞状细胞食管癌有关。在当前的研究中，通过使用序列数据在这个 500 kb 区域内鉴定了 17 个额外的推定微卫星标记，其中 7 个在英国和美国家族中显示出多态性。此外，我们对 TOC 最小区域非重复部分的完整序列分析在这些家族中的一个或两个中鉴定了 53 个新的和 6 个已知的单核苷酸多态性 (SNP)。通过对 7 个多态性标记和 59 个 SNP 中的 21 个进行单倍型分析，对 TOC 疾病位点进行进一步精细定位，使最小区域减少至 42.5 kb。一个已知基因和两个推定基因位于该区域内，但这些基因均未在其蛋白质编码区域内显示出特异病特异性突变。因此，必须考虑疾病基因作用的替代机制。
Tylosis (focal non-epidermolytic palmoplantar keratoderma) is associated with the early onset of squamous cell oesophageal cancer in three families. Linkage and haplotype analyses have previously mapped the tylosis with oesophageal cancer (TOC) locus to a 500-kb region on chromosome 17q25 that has also been implicated in sporadically occurring squamous cell oesophageal cancer. In the current study, 17 additional putative microsatellite markers were identified within this 500-kb region by using sequence data and seven of these were shown to be polymorphic in the UK and US families. In addition, our complete sequence analysis of the non-repetitive parts of the TOC minimal region identified 53 novel and six known single nucleotide polymorphisms (SNPs) in one or both of these families. Further fine mapping of the TOC disease locus by haplotype analysis of the seven polymorphic markers and 21 of the 59 SNPs allowed the reduction of the minimal region to 42.5 kb. One known and two putative genes are located within this region but none of these genes shows tylosis-specific mutations within their protein-coding regions. Alternative mechanisms of disease gene action must therefore be considered.