Chen Ying, Tan Ene-Choo
Population Genetics Programme, Defence Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, Kent Ridge, Singapore, Singapore, 117510.
J Hum Genet. 2004;49(4):209-214. doi: 10.1007/s10038-004-0130-y. Epub 2004 Mar 13.
The human Clock gene ( hClock) encodes the CLOCK protein essential for the function of the circadian system. We have screened the entire coding region, including the 5' and 3' untranslated regions (UTRs) and the flanking intronic regions, of the hClock gene for sequence variations in 70 unrelated Chinese Singaporeans with denaturing high-performance liquid chromatography (dHPLC). A total of 15 sequence variations were detected, five of which were novel. All involved single base changes. There were 12 substitutions and three insertions/deletions. All except one were found in the introns or the UTRs. Frequencies of the minor allele for all 15 polymorphisms ranged from 0.7% to almost 50%. For the eight sites whose minor allele frequency was found to be at least 10%, pair-wise comparisons revealed that all except one were in almost complete linkage disequilibrium. Our identification of additional single nucleotide polymorphisms in the hClock gene would provide markers whose frequencies could be established in the selected population and used for further analysis of the phenotypic effects. Our results would also be useful for better planning in the selection of polymorphisms for future genetic association studies involving the hClock gene.
人类生物钟基因（hClock）编码昼夜节律系统功能所必需的CLOCK蛋白。我们利用变性高效液相色谱法（dHPLC），对70名无亲缘关系的新加坡华人的hClock基因的整个编码区（包括5'和3'非翻译区（UTR）以及侧翼内含子区）进行了序列变异筛查。共检测到15个序列变异，其中5个是新发现的。所有变异均涉及单碱基变化。有12个替换和3个插入/缺失。除一个变异外，其他所有变异均位于内含子或UTR中。所有15个多态性的次要等位基因频率范围为0.7%至近50%。对于次要等位基因频率至少为10%的8个位点，成对比较显示，除一个位点外，其他所有位点几乎完全处于连锁不平衡状态。我们在hClock基因中鉴定出的额外单核苷酸多态性将提供一些标记，其频率可在选定人群中确定，并用于进一步分析表型效应。我们的结果对于更好地规划未来涉及hClock基因的遗传关联研究中多态性的选择也将是有用的。
