title: Signature of backward replication slippage at the copy number variation junction.
abstract: Copy number abnormalities such as deletions and duplications give rise to a variety of medical problems and also manifest innocuous genomic variations. Aberrant DNA replication is suggested as the mechanism underlying de novo copy number abnormalities, but the precise details have remained unknown. In our present study, we analyzed the del(2)(q13q14.2) chromosomal junction site observed in a woman with a recurrent pregnancy loss. Microarray analyses allowed us to precisely demarcate a 2.8 Mb deletion in this case, which does not appear in the database of human genomic variations. This deletion includes only one brain-specific gene that could not be related to the reproduction failure of the patient. At the junction of the deletion, we found that 11-13-nucleotide sequence, originally located at the proximal breakpoint region, was repeated four times with a single-nucleotide microhomology at the joint between each repeat. The proximal region and the distal region was finally joined with six-nucleotide microhomology. The structure of the junction is consistent with backward replication slippage proposed previously. Our data lend support to the notion that a common DNA replication-mediated pathway generates copy number variation in the human genome.
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.
authors.forename: Tamae
authors.initials: T
authors.lastname: Ohye
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Inagaki
authors.affiliation: Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ozaki
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics; D001483:Base Sequence; D002871:Chromosome Banding; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2; D056915:DNA Copy Number Variations; D004261:DNA Replication; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data