Alignment difficulty. Detecting alignments of short reads is more difficult in the presence of sequencing errors (represented as X's). (a) In the case of genome assembly, we may miss short overlaps between reads containing sequencing errors, particularly because the errors tend to occur at the ends of the reads. (b) To find variations between the sequenced genome and a reference genome, we typically first map the reads to the reference. However, reads containing variants (represented as stars) and sequencing errors will have too many mismatches and not align to their true genomic location.
Kelley et al. Genome Biology 2010 11:R116 doi:10.1186/gb-2010-11-11-r116