title: Chromosome-wide assessment of replication timing for human chromosomes 11q and 21q: disease-related genes in timing-switch regions.
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.
authors.affiliation: Division of Evolutionary Genetics, Department of Population Genetics, National Institute of Genetics, Yata 1111, Mishima, Shizuoka-ken 411-8540, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Asao
authors.initials: A
authors.lastname: Fujiyama
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ichiba
authors.forename: Masahira
authors.initials: M
authors.lastname: Hattori
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Yada
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sakaki
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Ikemura
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D003596:Cytosine; D004261:DNA Replication / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D006151:Guanosine; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D016196:S Phase / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D006151:Guanosine; D003596:Cytosine