Exome Sequencing
Exome-seq
Genetic variants that change protein sequences can be responsible for many Mendelian and common polygenic diseases, such as Alzheimer's disease. Identification of such variants is paramount for clinical diagnosis, understanding the disease mechanism and patient treatment. Exome sequencing seeks to identify variants in all protein-coding genes but for a fraction of the costs of whole-genome sequencing.
Challenges
- Human Exome represents 2% of genome, but contains 85% of known disease-causing variants
- Disadvantage: limited to what is known already
- Optimal mapping of spliced reads
- Sequencers overestimate base quality
- Separately mapped reads can miss correct indel alignments
- Correct genotyping and joining of samples to a joint genotype