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A systematic evaluation of hybridization-based mouse exome capture system.

Qingsong Gao, Wei Sun, Xintian You

|July 23, 2013

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Mouse exome capture systems based on C57BL/6J reference genomes show bias against divergent strains. Sufficient sequencing depth is crucial for accurate variant detection in hybrid mice, especially with greater sequence divergence.

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Area of Science:

Genomics
Comparative Genomics

Background:

Exome sequencing is vital for identifying mouse genetic variants.
Current mouse exome capture systems rely on the C57BL/6J reference genome.
Sequence divergence between mouse strains can impact capture efficiency.

Purpose of the Study:

To evaluate the impact of sequence divergence on mouse exome capture efficiency.
To assess the performance of C57BL/6J-based capture systems in divergent mouse strains.

Main Methods:

Utilized the Agilent SureSelect mouse exome capture system.
Performed exome sequencing on F1 hybrid mice from C57BL/6J x SPRET/EiJ cross.
Analyzed capture efficiency and variant detection bias.

Main Results:

C57BL/6J probes preferentially captured C57BL/6J alleles.
Capture bias increased with sequence divergence.
Low sequencing depth impaired variant detection, but this effect diminished with increased depth.

Conclusions:

C57BL/6J-based exome capture systems exhibit strain-specific biases.
Adequate sequencing depth is essential for accurate variant discovery in divergent mouse strains.
Consider sequence divergence when planning exome sequencing studies with C57BL/6J-based probes.