Method | Advantages | Limitations | Applications |
---|---|---|---|
Whole-exome sequencing or candidate exome capture | Customized, economical compared to WGS, manageable data size | Captures genetic variants only in the coding regions of the genome; inefficient hybridization step; high DNA input; susceptible to capture bias | SNP and indel discovery in coding exons; suitable for the identification of causal genes in high-penetrance Mendelian diseases |
Targeted re-sequencing | Customized, economical compared to WGS | Genetic variant discovery is limited by array design; high DNA input; inefficient hybridization step; captures only a small proportion of the genome | SNP and indel discovery; suitable for sequencing linkage intervals and genomic regions at or around associated signals |
Whole-genome sequencing | Uncovers genome-wide coding and non-coding variants, no capture bias | Expensive; very large dataset; analysis methods are still evolving | Genome-wide SNP, indel and CNV discovery; suitable for rare variant discovery in Mendelian, complex or sporadic traits |
Exome-chip | Cost-effective method for evaluating known rare variants (MAF of 1 to 5%) | Does not identify novel variants; limited to coding region; limited representation of intronic and regulatory variants | Genome-wide association analysis with rare variants |
RNA-Seq | Array-independent profiling of the transcriptome | High coverage required for the identification of low-copy transcripts; not applicable for the identification of variants that cause loss of protein; limited by tissue- or cell-type availability | Genome-wide expression profiling; alternative transcript identification; non-coding RNA detection; SNP profiling; eQTL analysis |
ChIP-Seq | Genome-wide profiling of epigenetic marks (DNA methylation and histone modifications) and cis-regulatory elements | Dependent on the quality of antibody; requires high input; analysis methods still evolving; high coverage needed for accurate profiling | DNA methylation; histone modifications; tissue-specific enhancer profiling |