Next-generation sequencing (NGS) is now routinely used to interrogate large sets of genes in a diagnostic setting. Regions of high sequence homology continue to be a major challenge for short-read technologies and can lead to false-positive and false-negative diagnostic errors.
Sequence of Exons 44 and 45 of CACNA1C for example, seems to be highly homologous with a region localized in a downstream position ( chr12:2,850,724-2,851,918).
Depending on the quality of the experiment, and the lenght of reads this region homology might generate some problems:
1- Many reads might have mapping quality = 0
2- If reads with Mapping Quality = 0 are not removed they will be used for coverage analysis ( usually they are not removed in commercial pipelines).
3- Mapping Quality = 0 reads might not be used in variant calling step (GATK).
The presence of many reads with mapping quality = 0 might be a problem, pay attention and check it out
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