Table 1.

Importance of the functional analysis in various types of human genetics studies

Analysis of Mendelian traits				Analysis of rare variants in complex traits
Interpretation of variants in previously mapped genes		Mapping genes by whole-genome/exome sequencing		Analysis of rare variants in candidate genes		Mapping genes by whole-genome/exome sequencing
Uncharacterized variants not known to be de novo	De novo mutations	Segregating variants	De novo mutations	Rare variants	De novo mutations	Rare variants	De novo mutations
Analysis of the functional effect and causality is essential	Usually regarded as sufficient evidence of functionality	Functional analysis is not essential to map genes but can potentially increase power	Functional analysis is essential for isolated mutations. Recurrence may provide a statistical argument in favor of functionality	Functional analysis was shown to increase power	Likely a sufficient evidence of functionality	Functional analysis was hypothesized to increase power	Functional analysis is essential for isolated mutations. Recurrence may provide a statistical argument in favor of functionality