Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher.
Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?
Some links on this page may take you to non-federal websites. Their policies may differ from this site.
INTRODUCTION Transposable elements (TEs), repeat expansions, and repeat-mediated structural rearrangements play key roles in chromosome structure and species evolution, contribute to human genetic variation, and substantially influence human health through copy number variants, structural variants, insertions, deletions, and alterations to gene transcription and splicing. Despite their formative role in genome stability, repetitive regions have been relegated to gaps and collapsed regions in human genome reference GRCh38 owing to the technological limitations during its development. The lack of linear sequence in these regions, particularly in centromeres, resulted in the inability to fully explore the repeat content of the human genome in the context of both local and regional chromosomal environments. RATIONALE Long-read sequencing supported the complete, telomere-to-telomere (T2T) assembly of the pseudo-haploid human cell line CHM13. This resource affords a genome-scale assessment of all human repetitive sequences, including TEs and previously unknown repeats and satellites, both within and outside of gaps and collapsed regions. Additionally, a complete genome enables the opportunity to explore the epigenetic and transcriptional profiles of these elements that are fundamental to our understanding of chromosome structure, function, and evolution. Comparative analyses reveal modes of repeat divergence, evolution, and expansion or contraction with locus-level resolution. RESULTS We implementedmore »Free, publicly-accessible full text available April 1, 2023
INTRODUCTION To faithfully distribute genetic material to daughter cells during cell division, spindle fibers must couple to DNA by means of a structure called the kinetochore, which assembles at each chromosome’s centromere. Human centromeres are located within large arrays of tandemly repeated DNA sequences known as alpha satellite (αSat), which often span millions of base pairs on each chromosome. Arrays of αSat are frequently surrounded by other types of tandem satellite repeats, which have poorly understood functions, along with nonrepetitive sequences, including transcribed genes. Previous genome sequencing efforts have been unable to generate complete assemblies of satellite-rich regions because of their scale and repetitive nature, limiting the ability to study their organization, variation, and function. RATIONALE Pericentromeric and centromeric (peri/centromeric) satellite DNA sequences have remained almost entirely missing from the assembled human reference genome for the past 20 years. Using a complete, telomere-to-telomere (T2T) assembly of a human genome, we developed and deployed tailored computational approaches to reveal the organization and evolutionary patterns of these satellite arrays at both large and small length scales. We also performed experiments to map precisely which αSat repeats interact with kinetochore proteins. Last, we compared peri/centromeric regions among multiple individuals to understand how thesemore »Free, publicly-accessible full text available April 1, 2023