English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Many genetic/genomic disorders are caused by genomic rearrangements. Standard methods can often characterize these variations only partly, e.g., copy number changes or breakpoints. It is important to fully understand the order and orientation of rearranged fragments, with precise breakpoints, to know the pathogenicity of the rearrangements.    Methods  We performed whole-genome-coverage nanopore sequencing of long DNA reads from four patients with chromosomal translocations. We identified rearrangements relative to a reference human genome, subtracted rearrangements shared by any of 33 control individuals, and determined the order and orientation of rearranged fragments, with our newly developed analysis pipeline.    Results  We describe the full characterization of complex chromosomal rearrangements, by filtering out genomic rearrangements seen in controls without the same disease, reducing the number of loci per patient from a few thousand to a few dozen. Breakpoint detection was very accurate; we usually see ~ 0 ± 1 base difference from Sanger sequencing-confirmed breakpoints. For one patient with two reciprocal chromosomal translocations, we find that the translocation points have complex rearrangements of multiple DNA fragments involving 5 chromosomes, which we could order and orient by an automatic algorithm, thereby fully reconstructing the rearrangement. A rearrangement is more than the sum of its parts: some properties, such as sequence loss, can be inferred only after reconstructing the whole rearrangement. In this patient, the rearrangements were evidently caused by shattering of the chromosomes into multiple fragments, which rejoined in a different order and orientation with loss of some fragments.    Conclusions  We developed an effective analytic pipeline to find chromosomal aberration in congenital diseases by filtering benign changes, only from long read sequencing. Our algorithm for reconstruction of complex rearrangements is useful to interpret rearrangements with many breakpoints, e.g., chromothripsis. Our approach promises to fully characterize many congenital germline rearrangements, provided they do not involve poorly understood loci such as centromeric repeats.

A pipeline for complete characterization of complex germline rearrangements from long DNA reads