A Critical Need for Clinical Context in the Genomic Era.

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Abstract

The family unit is central to understanding the relationship between genotype and phenotype. The power of genetics is a direct reflection of the probability of transmission of each allele to daughter cells during meiosis. The statistics of co-segregation allow the rigorous association of individual genotypes with precise phenotypes in families with relatively modest numbers of informative meioses. The causal chain also assumes a deleterious effect for the specific variant, its absence from the general population and independent evidence of a relevant biological role for the gene1. This approach has been used to identify numerous disease genes in the last three decades.