Dec 3, 2009

Breakpoint analysis of balanced chromosome rearrangements by next-generation paired-end sequencing

European Journal of Human Genetics : EJHG
Wei ChenHans-Hilger Ropers


Characterisation of breakpoints in disease-associated balanced chromosome rearrangements (DBCRs), which disrupt or inactivate specific genes, has facilitated the molecular elucidation of a wide variety of genetic disorders. However, conventional methods for mapping chromosome breakpoints, such as in situ hybridisation with fluorescent dye-labelled bacterial artificial chromosome clones (BAC-FISH), are laborious, time consuming and often with insufficient resolution to unequivocally identify the disrupted gene. By combining DNA array hybridisation with chromosome sorting, the efficiency of breakpoint mapping has dramatically improved. However, this can only be applied when the physical properties of the derivative chromosomes allow them to be flow sorted. To characterise the breakpoints in all types of balanced chromosome rearrangements more efficiently and more accurately, we performed massively parallel sequencing using Illumina 1G analyser and ABI SOLiD systems to generate short sequencing reads from both ends of DNA fragments. We applied this method to four different DBCRs, including two reciprocal translocations and two inversions. By identifying read pairs spanning the breakpoints, we were able to map the breakpoints to a ...Continue Reading

  • References13
  • Citations25


  • References13
  • Citations25


Mentioned in this Paper

Genetic Disorders Screening
Chromosome Breakpoints
Gene Amplification Technique
Bacterial Artificial Chromosomes
Fluorescent stain
Autosome Abnormalities
Sorting - Cell Movement
Massively-Parallel Sequencing
Chromosome Breaks

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