title: The constitutional t(11;22): implications for a novel mechanism responsible for gross chromosomal rearrangements.
abstract: The constitutional t(11;22)(q23;q11) is the most common recurrent non-Robertsonian translocation in humans. The breakpoint sequences of both chromosomes are characterized by several hundred base pairs of palindromic AT-rich repeats (PATRRs). Similar PATRRs have also been identified at the breakpoints of other nonrecurrent translocations, suggesting that PATRR-mediated chromosomal translocation represents one of the universal pathways for gross chromosomal rearrangement in the human genome. We propose that PATRRs have the potential to form cruciform structures through intrastrand-base pairing in single-stranded DNA, creating a source of genomic instability and leading to translocations. Indeed, de novo examples of the t(11;22) are detected at a high frequency in sperm from normal healthy males. This review synthesizes recent data illustrating a novel paradigm for an apparent spermatogenesis-specific translocation mechanism. This observation has important implications pertaining to the predominantly paternal origin of de novo gross chromosomal rearrangements in humans.
authors.affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan. kura@fujita-hu.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Kurahashi
authors.forename: H
authors.initials: H
authors.lastname: Inagaki
authors.forename: T
authors.initials: T
authors.lastname: Ohye
authors.forename: H
authors.initials: H
authors.lastname: Kogo
authors.forename: M
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Tong
authors.forename: B S
authors.initials: BS
authors.lastname: Emanuel
mesh_terms: D020856:AT Rich Sequence; D002869:Chromosome Aberrations; D056905:Chromosome Breakpoints; D002880:Chromosomes, Human, Pair 11; D002892:Chromosomes, Human, Pair 22; D045566:DNA, Cruciform; D004277:DNA, Single-Stranded / Q000235:genetics; D005260:Female; D015894:Genome, Human; D042822:Genomic Instability; D006801:Humans; D008297:Male; D012091:Repetitive Sequences, Nucleic Acid; D013091:Spermatogenesis; D014178:Translocation, Genetic
chemical_list: D045566:DNA, Cruciform; D004277:DNA, Single-Stranded