TY - JOUR
T1 - Recombination between heterologous human acrocentric chromosomes
AU - Human Pangenome Reference Consortium
AU - Guarracino, Andrea
AU - Buonaiuto, Silvia
AU - de Lima, Leonardo Gomes
AU - Potapova, Tamara
AU - Rhie, Arang
AU - Koren, Sergey
AU - Rubinstein, Boris
AU - Fischer, Christian
AU - Abel, Haley J.
AU - Antonacci-Fulton, Lucinda L.
AU - Asri, Mobin
AU - Baid, Gunjan
AU - Baker, Carl A.
AU - Belyaeva, Anastasiya
AU - Billis, Konstantinos
AU - Bourque, Guillaume
AU - Carroll, Andrew
AU - Chaisson, Mark J.P.
AU - Chang, Pi Chuan
AU - Chang, Xian H.
AU - Cheng, Haoyu
AU - Chu, Justin
AU - Cody, Sarah
AU - Cook, Daniel E.
AU - Cook-Deegan, Robert M.
AU - Cornejo, Omar E.
AU - Diekhans, Mark
AU - Doerr, Daniel
AU - Ebert, Peter
AU - Ebler, Jana
AU - Eichler, Evan E.
AU - Eizenga, Jordan M.
AU - Fairley, Susan
AU - Fedrigo, Olivier
AU - Felsenfeld, Adam L.
AU - Feng, Xiaowen
AU - Flicek, Paul
AU - Formenti, Giulio
AU - Frankish, Adam
AU - Fulton, Robert S.
AU - Gao, Yan
AU - Garg, Shilpa
AU - Garrison, Nanibaa’ A.
AU - Giron, Carlos Garcia
AU - Green, Richard E.
AU - Groza, Cristian
AU - Haggerty, Leanne
AU - Hall, Ira
AU - Harvey, William T.
AU - Haukness, Marina
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/5/11
Y1 - 2023/5/11
N2 - 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 duplications1,2. 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 homology3, 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 Consortium4 (HPRC), we find that contigs from all of the SAACs form a community. A variation graph5 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 recombination6,7. The pseudo-homologous regions include sequences that have previously been shown to lie at the breakpoint of Robertsonian translocations8, 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 ago9.
AB - 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 duplications1,2. 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 homology3, 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 Consortium4 (HPRC), we find that contigs from all of the SAACs form a community. A variation graph5 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 recombination6,7. The pseudo-homologous regions include sequences that have previously been shown to lie at the breakpoint of Robertsonian translocations8, 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 ago9.
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U2 - 10.1038/s41586-023-05976-y
DO - 10.1038/s41586-023-05976-y
M3 - Article
C2 - 37165241
AN - SCOPUS:85158868267
SN - 0028-0836
VL - 617
SP - 335
EP - 343
JO - Nature
JF - Nature
IS - 7960
ER -