Approach | Applies to | Advantages | Disadvantages |
---|---|---|---|
Candidate gene | Any disease | Easy to perform for one or two genes; requires no mapping, can directly identify the causative variant/mutation | Relies heavily on current biological knowledge; success rate very low |
Genetic mapping by karyotyping | Any disease | Easy to perform; no familial cases required; can detect (large) balanced events | Low resolution, only detects large chromosomal aberrations; mutation detection requires second step |
Genetic mapping by linkage analysis | Inherited disease | Easy to perform | Requires large families, often identifies large loci; mutation detection requires second step |
Genetic mapping by homozygosity mapping | Recessive monogenic diseases | Small families can be used | Most useful for consanguineous families; often identifies large loci; mutation detection requires second step |
Genetic mapping by CNV analysis | Monogenic/monolocus disease | High resolution CNV screening; no familial cases required; can potentially identify small loci | Only investigates CNVs; cannot detect balanced events, no base-pair resolution; mutation detection requires second step |
Whole exome sequencing (WES) | Any disease | Base-pair resolution exome-wide; detects most types of genomic variation; can directly identify the causative variant/mutation | Unable to detect non-coding variants; limited resolution for CNVs and other structural variation; coverage variability due to enrichment process; relatively expensive |
Whole genome sequencing (WGS) | Any disease | Base-pair resolution genome-wide; detects all types of genomic variation; can directly identify the causative variant/mutation | Data analysis complex; even more expensive than exome sequencing |