Table 1 A comparison of the methodologies, strengths and weaknesses of Mendelian gene discovery, Association studies and fSNPd
Mendelian gene discovery | Genome Wide Association studies | fSNPd | |
|---|---|---|---|
Minimum number of affected individuals/families | 2 to 10 families | Typically >2000 | 30–200 individuals |
Scope | Usually exome | Genome | Exome |
Approach | Usually candidate | Non-candidate | Non-candidate |
Proof | If linkage p < 0.05 +/− additional proofs | Conventional threshold is p < 5 × 10−8 | p < 0.01 after correction for SNPs assessed |
Effect on phenotype | Fully penetrant for recessive and X-linked; dominant penetrance 0.33 to 1.0 | Usually very small, e.g. odds ratio < 1.33 for a risk SNP. | Non-penetrant before environmental triggers; presumed 0.5–1.0 penetrance after trigger. |
Approximate cost to perform | £10,000–£100,000 | £300,000–£8,000,000 | £15,000–£50,000 |
Number of phenotype-associated genes identified | 1 | >1 | >1 |
Are changes discovered easily functionally assessed | Yes | Usually No | Yes |
Ability to cope with non-genetic cases | Poor | Moderate | Good |