Translocation breakpoint mapping and sequence analysis in three monosomy 1p36 subjects with der(1)t(1;1)(p36;q44) suggest mechanisms for telomere capture in stabilizing de novo terminal rearrangements

Hum Genet. 2004 Jan;114(2):198-206. doi: 10.1007/s00439-003-1029-y. Epub 2003 Oct 25.


Monosomy 1p36 results from a variety of chromosome rearrangements, including terminal deletions, interstitial deletions, derivative chromosomes, and complex rearrangements. Our previous molecular studies on a large cohort of monosomy 1p36 subjects suggest that a significant percentage of terminal deletions of 1p36 are stabilized by the acquisition of telomeric sequences from other chromosome ends, forming derivative chromosomes (i.e., "telomere capture"). However, the molecular mechanism(s) that results in and/or stabilizes terminal deletions of 1p36 by telomere capture is poorly understood. In this report, we have mapped the translocation breakpoints in three subjects with der(1)t(1;1)(p36;q44) chromosomes by fluorescence in situ hybridization (FISH). These results indicate that the breakpoint locations are variable in all three subjects, with no common 1p deletion or 1q translocation breakpoints. In addition, sequence analysis of the 1p and 1q breakpoint-containing clones did not identify homologous sequences or low-copy repeats in the breakpoint regions, suggesting that nonallelic homologous recombination did not play a role in mediating these rearrangements. Microsatellite marker analysis indicates that two of the three derivative chromosomes were formed by intra-chromosomal rearrangements. These data are consistent with a number of recent reports in other model organisms that suggest break-induced replication at the site of a double-strand break may act as a mechanism of telomere capture by generating nonreciprocal translocations from terminally deleted chromosomes. Alternative models are also discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Aberrations*
  • Chromosome Banding
  • Chromosome Disorders
  • Chromosome Mapping
  • Chromosomes, Human, Pair 1 / genetics*
  • Cytogenetic Analysis / methods
  • DNA / genetics
  • DNA Probes
  • DNA Replication / genetics
  • Gene Deletion*
  • Gene Rearrangement
  • Humans
  • In Situ Hybridization, Fluorescence
  • Monosomy / genetics*
  • Repetitive Sequences, Nucleic Acid / genetics
  • Telomere / genetics*
  • Translocation, Genetic*


  • DNA Probes
  • DNA