Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data

GM Cooper, J Shendure - Nature Reviews Genetics, 2011 - nature.com
Nature Reviews Genetics, 2011nature.com
Genome and exome sequencing yield extensive catalogues of human genetic variation.
However, pinpointing the few phenotypically causal variants among the many variants
present in human genomes remains a major challenge, particularly for rare and complex
traits wherein genetic information alone is often insufficient. Here, we review approaches to
estimate the deleteriousness of single nucleotide variants (SNVs), which can be used to
prioritize disease-causal variants. We describe recent advances in comparative and …
Abstract
Genome and exome sequencing yield extensive catalogues of human genetic variation. However, pinpointing the few phenotypically causal variants among the many variants present in human genomes remains a major challenge, particularly for rare and complex traits wherein genetic information alone is often insufficient. Here, we review approaches to estimate the deleteriousness of single nucleotide variants (SNVs), which can be used to prioritize disease-causal variants. We describe recent advances in comparative and functional genomics that enable systematic annotation of both coding and non-coding variants. Application and optimization of these methods will be essential to find the genetic answers that sequencing promises to hide in plain sight.
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