Next-generation sequencing strategies enable routine detection of balanced chromosome rearrangements for clinical diagnostics and genetic research.

摘要: The contribution of balanced chromosomal rearrangements to complex disorders remains unclear because they are not detected routinely by genome-wide microarrays and clinical localization is imprecise. Failure consider these events bypasses a potentially powerful complement single nucleotide polymorphism copy-number association approaches disorders, where much the heritability unexplained. To capitalize on this genetic resource, we have applied optimized sequencing analysis strategies test whether high-impact variants can be mapped at reasonable cost throughput. By using whole-genome multiplexing strategy, rearrangement breakpoints could delineated fraction standard sequencing. For already regionally karyotyping fluorescence in situ hybridization, targeted approach enabled capture multiple simultaneously. Importantly, strategy permitted unique alignment up 97% repeat-masked sequences in regions. Genome-wide analyses estimate that only 3.7% bases should omitted from genomic DNA experiments. Illustrating power approaches, were rapidly defined base pair resolution revealed unexpected sequence complexity, such as co-occurrence inversion translocation an underlying feature karyotypically alterations. These findings implications ranging genome annotation de novo assemblies enable screens for structural variations comparable practice.