A Critical Need for Clinical Context in the Genomic Era
作者： Calum A. MacRae
DOI: 10.1161/CIRCULATIONAHA.115.018371
关键词: Genomics 、 Cosegregation 、 Biology 、 Mutation (genetic algorithm) 、 Context (language use) 、 Allele 、 Genetics 、 Population 、 Genotype 、 Gene
摘要: The family unit is central to understanding the relationship between genotype and phenotype. power of genetics a direct reflection probability transmission each allele daughter cells during meiosis. statistics cosegregation allow rigorous association individual genotypes with precise phenotypes even in families relatively modest numbers informative meioses. chain causality also assumes deleterious effect for specific variant, its absence from general population, independent evidence relevant biological role gene.1 This approach has been used identify numerous disease genes last 3 decades. Article see p 1013 Once initial gene established through such segregation studies multiple families, threshold associating variant naturally lowered. Early mutations add support case causality, but all too rapidly, “mutation” databases become diluted spurious variants as only known are studied smaller families. As larger control cohorts have available sequencing data grown exponentially, contamination mutation apparently benign variation more obvious.2 perils case-based amplified by growing reports oligogenic combinations causal …
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