A Bioinformatics paper from Jonathan Pritchard's lab at the University of Chicago looked into how SNP variation affects read-mapping reliability, particularly in relation to allele-specific expression. "We have shown here that differential mapping of SNP alleles can greatly affect inferences that rely on quantifying DNA or RNA with next-generation sequencing data. This may be especially problematic in studies that aim to detect allele-specific differences in gene expression, transcription factor binding or other related applications," the authors write.
Dan Koboldt at MassGenomics weighs in on the study. "Your reaction might be to shrug, since Illumina/Solexa now routinely generates 76-bp and 100-bp reads," he says, adding that there are "a number of reasons why this might not address the bias issue" including that the lengths of alignment seeds have not changed and that many groups are still rely on shorter reads.