A systematic evaluation of hybridization-based mouse exome capture system

Background: With great success in the field of human genetics, exome capture systems have been developed and applied for mutation discovery in mice. The current hybridization-based mouse exome capture systems were all designed based on the genome reference sequences of the C57BL/6J strain. Given the substantial sequence divergence between C57BL/6J and some remotely related strains, it needs to be systematically evaluated whether the sequence divergence could affect the efficiency of the available exome capture system when it were applied in the study of those strains, especially in a mixed genetic background. Results: Using a commercial mouse exome capture system, we performed exome sequencing in a F1 hybrid mouse between C57BL/6J and a remotely related strain, SPRET/EiJ. Our results clearly showed that the exome probes captured the sequences derived from C57BL/6J alleles more efficiently and the bias was stronger for the probes targeting regions with higher sequence divergence. At low sequencing depth, this bias also affected the efficiency of variant detection. However, the effect became negligible when sequencing depth got sufficiently high. Conclusion: Supplied with sufficient sequencing depth, current hybridization-based mouse exome capture system could be efficiently applied in the mouse strains remotely related to C57BL/6J, although its performance could be negatively affected by sequence divergence.