title: Regions of genomic instability on 22q11 and 11q23 as the etiology for the recurrent constitutional t(11;22).
abstract: The constitutional t(11;22)(q23;q11) is the only known recurrent, non-Robertsonian translocation. To analyze the genomic structure of the breakpoint, we have cloned the junction fragments from the der(11) and der(22) of a t(11;22) balanced carrier. On chromosome 11 the translocation occurs within a short, palindromic AT-rich region (ATRR). Likewise, the breakpoint on chromosome 22 has been localized within an ATRR that is part of a larger palindrome. Interestingly, the 22q11 breakpoint falls within one of the 'unclonable' gaps in the genomic sequence. Further, a sequenced chromosome 11 BAC clone, spanning the t(11;22) breakpoint in 11q23, is deleted within the palindromic ATRR, suggesting instability of this region in bacterial clones. Several unrelated t(11;22) families demonstrate similar breakpoints on both chromosomes, indicating that their translocations are within the same palindrome. It is likely that the palindromic ATRRs produce unstable DNA structures in 22q11 and 11q23 that are responsible for the recurrent t(11;22) translocation.
authors.affiliation: Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia, PA 19104, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kurahashi
authors.forename: T H
authors.initials: TH
authors.lastname: Shaikh
authors.forename: P
authors.initials: P
authors.lastname: Hu
authors.forename: B A
authors.initials: BA
authors.lastname: Roe
authors.forename: B S
authors.initials: BS
authors.lastname: Emanuel
authors.forename: M L
authors.initials: ML
authors.lastname: Budarf
mesh_terms: D001483:Base Sequence; D019457:Chromosome Breakage; D002873:Chromosome Fragility; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D006801:Humans; D006822:Hybrid Cells; D008954:Models, Biological; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic
chemical_list: D004247:DNA