The emerging role of structural variations in common disorders: initial findings and discovery challenges

Abstract

After the successful discoveries of genetic associations for common disorders using single nucleotide polymorphisms (SNPs) in genome-wide association scans (GWAS), new efforts are ongoing to evaluate the contribution of structural variations to disease, mainly in the form of copy number variants (CNVs). These are mainly motivated after the identification of consistent relationships between CNVs and disease, and the recognition that there is not a unique human genome sequence at the structural level. The current knowledge reflects that few regions of the genome are free of structural rearrangements and that genes with a role in response to environment are particularly prone to contain CNVs with phenotypic consequences. In the following years many individuals will be sequenced, defining the variability of the genome at the sequence and structural levels. The characterization of regions of the genome that are variable in the orientation and order of genes and genomic segments between individuals is a major challenge, which can only be reliably tackled by high-throughput sequencing technologies and bioinformatics designs. The goal is to explore the whole set of genome diversity to extract the molecular basis of disorders that could affect any individual in the population and that is inherent to the adaptation of human groups to environmental conditions.