Chromosome-wide assessment of replication timing for human chromosomes 11q and 21q: disease-related genes in timing-switch regions
Chromosome-wide assessment of replication timing for human chromosomes 11q and 21q: disease-related genes in timing-switch regions
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DOI：
10.1093/hmg/11.1.13
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发表时间：
2002-01-01
影响因子：
3.5
通讯作者：
Ikemura, T
中科院分区：
文献类型：
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作者：
Watanabe, Y;Fujiyama, A;Ikemura, T
人类基因组序列的完成将极大地促进生物科学新分支的发展，并为生物医学研究提供基础知识。我们利用序列信息测量了人类染色体11q和21q整个长度的复制时间。在序列级别上定义了在S阶段早期或晚期复制的兆级大小的区域（因此早期/晚期转换）。早期区比晚期区富含GC和基因，早期/晚期转变主要发生在与GC%转变相同或接近GC%转变的位置。我们还发现单核苷酸多态性（SNP）频率在复制后期和复制过渡区较高。在早/晚过渡区，癌症相关基因集中出现，包括编码cyclin D1 （BCL1）、FGF4 （KFGF）、TIAM7和FLI1的CCND1。过渡区包含其他疾病相关基因，包括与家族性阿尔茨海默病（AD1）相关的APP、与家族性肌萎缩侧索硬化症（ALS1）相关的SOD1和与苯丙酮尿症相关的PTS。这些发现讨论了关于预测增加DNA损伤发生在复制过渡区。我们建议全基因组复制时间评估作为识别疾病相关基因的有效策略。
The completion of the human genome sequence will greatly accelerate development of a new branch of bioscience and provide fundamental knowledge to biomedical research. We used the sequence information to measure replication timing of the entire lengths of human chromosomes 11q and 21q. Megabase-sized zones that replicate early or late in S phase (thus early/late transition) were defined at the sequence level. Early zones were more GC-rich and gene-rich than were late zones, and early/late transitions occurred primarily at positions identical to or near GC% transitions. We also found the single nucleotide polymorphism (SNP) frequency was high in the late-replicating and replication-transition regions. In the early/late transition regions, concentrated occurrence of cancer-related genes that include CCND1 encoding cyclin D1 (BCL1), FGF4 (KFGF), TIAM7 and FLI1, was observed. The transition regions contained other disease-related genes including APP associated with familial Alzheimer's disease (AD1), SOD1 associated with familial amyotrophic lateral sclerosis (ALS1) and PTS associated with phenylketonuria. These findings are discussed with respect to the prediction that increased DNA damage occurs in replication-transition regions. We propose that genome-wide assessment of replication timing serves as an efficient strategy for identifying disease-related genes.