Helmholtz Gemeinschaft


Recombination between heterologous human acrocentric chromosomes

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supplementary Information)

Item Type:Article
Title:Recombination between heterologous human acrocentric chromosomes
Creators Name:Guarracino, A. and Buonaiuto, S. and de Lima, L.G. and Potapova, T. and Rhie, A. and Koren, S. and Rubinstein, B. and Fischer, C. and Gerton, J.L. and Phillippy, A.M. and Colonna, V. and Garrison, E.
Abstract:The short arms of the human acrocentric chromosomes 13, 14, 15, 21 and 22 (SAACs) share large homologous regions, including ribosomal DNA repeats and extended segmental duplications. Although the resolution of these regions in the first complete assembly of a human genome—the Telomere-to-Telomere Consortium’s CHM13 assembly (T2T-CHM13)—provided a model of their homology, it remained unclear whether these patterns were ancestral or maintained by ongoing recombination exchange. Here we show that acrocentric chromosomes contain pseudo-homologous regions (PHRs) indicative of recombination between non-homologous sequences. Utilizing an all-to-all comparison of the human pangenome from the Human Pangenome Reference Consortium (HPRC), we find that contigs from all of the SAACs form a community. A variation graph constructed from centromere-spanning acrocentric contigs indicates the presence of regions in which most contigs appear nearly identical between heterologous acrocentric chromosomes in T2T-CHM13. Except on chromosome 15, we observe faster decay of linkage disequilibrium in the pseudo-homologous regions than in the corresponding short and long arms, indicating higher rates of recombination. The pseudo-homologous regions include sequences that have previously been shown to lie at the breakpoint of Robertsonian translocations, and their arrangement is compatible with crossover in inverted duplications on chromosomes 13, 14 and 21. The ubiquity of signals of recombination between heterologous acrocentric chromosomes seen in the HPRC draft pangenome suggests that these shared sequences form the basis for recurrent Robertsonian translocations, providing sequence and population-based confirmation of hypotheses first developed from cytogenetic studies 50 years ago.
Keywords:Chromosomes, DNA Recombination, Genetic Variation, Genome Evolution
Publisher:Nature Publishing Group
Page Range:335-343
Date:11 May 2023
Additional Information:Ashley D. Sanders is a member of the Human Pangenome Reference Consortium
Official Publication:https://doi.org/10.1038/s41586-023-05976-y
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library