Complete genomic and epigenetic maps of human centromeres

Abstract

Existing human genome assemblies have almost entirely excluded highly repetitive sequences within and near centromeres, limiting our understanding of their sequence, evolution, and essential role in chromosome segregation. Here, we present an extensive study of newly assembled peri/centromeric sequences representing 6.2% (189.9 Mb) of the first complete, telomere-to-telomere human genome assembly (T2T-CHM13). We discovered novel patterns of peri/centromeric repeat organization, variation, and evolution at both large and small length scales. We also found that inner kinetochore proteins tend to overlap the most recently duplicated subregions within centromeres. Finally, we compared chromosome X centromeres across a diverse panel of individuals and uncovered structural, epigenetic, and sequence variation at single-base resolution across these regions. In total, this work provides an unprecedented atlas of human centromeres to guide future studies of their complex and critical functions as well as their unique evolutionary dynamics.

DeepConsensus: Gap-Aware Sequence Transformers for Sequence Correction

“…Pacific Biosciences (PacBio) uses repeated sequencing of a circular molecule to build consensus across time 2 . The accuracy of these approaches, and the manner they fail, ultimately limits the read lengths of these methods and the analyzable regions of the genome 3,4…”

HORmon: automated annotation of human centromeres

“…Datasets. We extracted the alpha satellite arrays from the assembly (public release v1.0) of the effectively haploid CHM13 human cell line constructed by the T2T Consortium (Miga et al, 2020;, Nurk et al, 2021, Altemose et al, 2021. We also extracted the alpha satellite array of the newly assembled centromere of chromosome X from HG002 cell line sequenced by the Human Pangenome Reference Consortium.…”

“…HORmon launches CentromereArchitect (Dvorkina et al, 2021) to generate the initial monomer-set and further modifies it by using the monomer-HOR feedback loop described in the Methods section (Figure HORmonPipeline). Supplementary Note "HORmon monomer naming" describes how HORmon assigns names to monomers and provides correspondence between these names and the traditional names described in Uralsky et al, 2019. Since CentromereArchitect identifies many infrequent monomers, comparing its monomer-set with the previously identified monomer-sets, e.g., the monomer-set MonomersT2T (Altemose et al, 2021) used by the T2T consortium (based on the monomer-set derived in Shepelev et al 2015 andUralsky et al, 2019), is not straightforward. HORmon thus filters the monomer-set generated by CentromereArchitect as described below.…”

“…Recent advances in long-read sequencing technologies led to rapid progress in centromere assembly in the last year , Nurk et al, 2020, Nurk et al, 2021, Altemose et al, 2021 and, for the first time, opened a possibility to address the long-standing questions about the architecture and evolution of human centromeres (Rice, 2019, Thakur et al, 2021. Alpha satellite arrays of "live" human centromeres that organize the kinetochore (which we refer to simply as centromeres) are tandem DNA repeats that are formed by units repeating thousands of times with limited nucleotide-level variations but extensive variations in copy numbers in the human population (Black and Giunta, 2018).…”

Complex population structure and haplotype patterns in Western Europe honey bee from sequencing a large panel of haploid drones

“…However, the AvaI repeats only represent a very small fraction of the centromeric regions described, with the largest one only covering 14 kb [33], whereas the estimation of the extent of the centromeres, based on a GC content lower than the genome average is much larger although imprecise and supposes a similar organization as for the AT-rich alpha-satellite repeats in vertebrates, such as human [69].…”