Figure 1

The basis of translocation mapping from paired-end sequencing. (a) Paired end sequencing is based on sequencing a short sequence of nucleotides of each end of fragmented and amplified genomic DNA. Reads without the desired length are filtered out. All reads are aligned to a reference genome. The average number of reads per genomic locus is called the coverage of the genome of the sequenced sample. A high coverage (20× to 40×) is needed for detection of point mutations while a much lower coverage is required for other analysis such as copy number and mapping of translocations. The number of reads that map to a locus can be regarded as a function of the number of copies of that locus. As reads can be binned across windows the coverage does not need to be high for such analyses. (b) When a part of a chromosome is fused to a part of another chromosome the read from this region will have a sequence in one end that maps to one chromosome and the other end maps to another. When this pattern is consistent over several reads the translocations can be precisely mapped. Intrachromosomal rearrangements are mapped the same way. (c) A circos plot of a breast cancer genome. The chromosomes are arranged as a circle from chromosome 1 to the sex chromosomes X and Y. The outer part of the circle shows the chromosomes with cytoband information. The blue line represents the copy number at the given loci. The lines in the middle represent translocations. The inter-chromosomal translocations are in purple and the intra-chromosomal translocations are shown in green. Part (c) is modified from Russnes et al. [21].