title: Frequent translocations occur between low copy repeats on chromosome 22q11.2 (LCR22s) and telomeric bands of partner chromosomes.
abstract: The chromosome 22q11.2 region is susceptible to rearrangements, mediated by low copy repeats (LCR22s). Deletions and duplications are mediated by homologous recombination events between LCR22s. The recurrent balanced constitutional translocation t(11;22)(q23;q11) breakpoint occurs in an LCR22 and is mediated by double strand breaks in AT-rich palindromes on both chromosomes 11 and 22. Recently, two cases of a t(17;22)(q11;q11) were reported, mediated by a similar mechanism (21). Except for these constitutional translocations, the molecular basis for non-recurrent, reciprocal 22q11.2 translocations is not known. To determine whether there are specific mechanisms that could mediate translocations, we analyzed cell lines derived from 14 different individuals by genotyping and FISH mapping. Somatic cell hybrid analysis was carried out for four cell lines. In five cell lines, the translocation breakpoints occurred in the same LCR22 as for the t(11;22) translocation, suggesting that similar molecular mechanisms are responsible. An additional three occurred in other LCR22s, and six were in non-LCR22 regions, mostly in the proximal half of the 22q11.2 region. The translocation breakpoints on the partner chromosomes were all located in the telomeric bands, proximal to the most telomeric unique sequence probe, in eight cell lines and distal to those loci in six. Therefore, several of the breakpoints were found to occur in the vicinity of highly dynamic regions of the genome, 22q11.2 and telomeric bands. We hypothesize that these regions are more susceptible to breakage and repair, resulting in translocations.
authors.affiliation: Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Spiteri
authors.forename: Melanie
authors.initials: M
authors.lastname: Babcock
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Kashork
authors.forename: Keiko
authors.initials: K
authors.lastname: Wakui
authors.forename: Swarna
authors.initials: S
authors.lastname: Gogineni
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lewis
authors.forename: Kisa M
authors.initials: KM
authors.lastname: Williams
authors.forename: Shinsei
authors.initials: S
authors.lastname: Minoshima
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Lorraine
authors.initials: L
authors.lastname: Potocki
authors.forename: Venkat
authors.initials: V
authors.lastname: Pulijaal
authors.forename: Alan
authors.initials: A
authors.lastname: Shanske
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: Bernice E
authors.initials: BE
authors.lastname: Morrow
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D019457:Chromosome Breakage / Q000235:genetics*; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D020080:Tandem Repeat Sequences / Q000235:genetics*; D016615:Telomere / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*