Chromosome-wide assessment of replication timing for human chromosomes 11q and 21q: Disease-related genes in timing-switch regions

Yoshihisa Watanabe, Asao Fujiyama, Yuta Ichiba, Masahira Hattori, Tetsushi Yada, Yoshiyuki Sakaki, Toshimichi Ikemura

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

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), TIAM1 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.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
JournalHuman Molecular Genetics
Volume11
Issue number1
Publication statusPublished - 2002 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Watanabe, Y., Fujiyama, A., Ichiba, Y., Hattori, M., Yada, T., Sakaki, Y., & Ikemura, T. (2002). Chromosome-wide assessment of replication timing for human chromosomes 11q and 21q: Disease-related genes in timing-switch regions. Human Molecular Genetics, 11(1), 13-21.