Complete genomic and epigenetic maps of human centromeres

Nicolas Altemose; Glennis A. Logsdon; Andrey V. Bzikadze; Pragya Sidhwani; Sasha A. Langley; Gina V. Caldas; Savannah J. Hoyt; Lev Uralsky; Fedor D. Ryabov; Colin J. Shew; Michael E.G. Sauria; Matthew Borchers; Ariel Gershman; Alla Mikheenko; Valery A. Shepelev; Tatiana Dvorkina; Olga Kunyavskaya; Mitchell R. Vollger; Arang Rhie; Ann M. McCartney; Mobin Asri; Ryan Lorig-Roach; Kishwar Shafin; Julian K. Lucas; Sergey Aganezov; Daniel Olson; Leonardo Gomes de Lima; Tamara Potapova; Gabrielle A. Hartley; Marina Haukness; Peter Kerpedjiev; Fedor Gusev; Kristof Tigyi; Shelise Brooks; Alice Young; Sergey Nurk; Sergey Koren; Sofie R. Salama; Benedict Paten; Evgeny I. Rogaev; Aaron Streets; Gary H. Karpen; Abby F. Dernburg; Beth A. Sullivan; Aaron F. Straight; Travis J. Wheeler; Jennifer L. Gerton; Evan E. Eichler; Adam M. Phillippy; Winston Timp; Megan Y. Dennis; Rachel J. O'Neill; Justin M. Zook; Michael C. Schatz; Pavel A. Pevzner; Mark Diekhans; Charles H. Langley; Ivan A. Alexandrov; Karen H. Miga

doi:10.1126/science.abl4178

Complete genomic and epigenetic maps of human centromeres

Nicolas Altemose, Glennis A. Logsdon, Andrey V. Bzikadze, Pragya Sidhwani, Sasha A. Langley, Gina V. Caldas, Savannah J. Hoyt, Lev Uralsky, Fedor D. Ryabov, Colin J. Shew, Michael E.G. Sauria, Matthew Borchers, Ariel Gershman, Alla Mikheenko, Valery A. Shepelev, Tatiana Dvorkina, Olga Kunyavskaya, Mitchell R. Vollger, Arang Rhie, Ann M. McCartneyMobin Asri, Ryan Lorig-Roach, Kishwar Shafin, Julian K. Lucas, Sergey Aganezov, Daniel Olson, Leonardo Gomes de Lima, Tamara Potapova, Gabrielle A. Hartley, Marina Haukness, Peter Kerpedjiev, Fedor Gusev, Kristof Tigyi, Shelise Brooks, Alice Young, Sergey Nurk, Sergey Koren, Sofie R. Salama, Benedict Paten, Evgeny I. Rogaev, Aaron Streets, Gary H. Karpen, Abby F. Dernburg, Beth A. Sullivan, Aaron F. Straight, Travis J. Wheeler, Jennifer L. Gerton, Evan E. Eichler, Adam M. Phillippy, Winston Timp, Megan Y. Dennis, Rachel J. O'Neill, Justin M. Zook, Michael C. Schatz, Pavel A. Pevzner, Mark Diekhans, Charles H. Langley, Ivan A. Alexandrov, Karen H. Miga

Whiting School of Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, and functions, which include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere human genome assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric and centromeric repeats, which constitute 6.2% of the genome (189.9 megabases). Detailed maps of these regions revealed multimegabase structural rearrangements, including in active centromeric repeat arrays. Analysis of centromere-associated sequences uncovered a strong relationship between the position of the centromere and the evolution of the surrounding DNA through layered repeat expansions. Furthermore, comparisons of chromosome X centromeres across a diverse panel of individuals illuminated high degrees of structural, epigenetic, and sequence variation in these complex and rapidly evolving regions.

Original language	English (US)
Article number	eabl4178
Journal	Science
Volume	376
Issue number	6588
DOIs	https://doi.org/10.1126/science.abl4178
State	Published - Apr 1 2022

ASJC Scopus subject areas

General

Access to Document

10.1126/science.abl4178

Cite this

Altemose, N., Logsdon, G. A., Bzikadze, A. V., Sidhwani, P., Langley, S. A., Caldas, G. V., Hoyt, S. J., Uralsky, L., Ryabov, F. D., Shew, C. J., Sauria, M. E. G., Borchers, M., Gershman, A., Mikheenko, A., Shepelev, V. A., Dvorkina, T., Kunyavskaya, O., Vollger, M. R., Rhie, A., ... Miga, K. H. (2022). Complete genomic and epigenetic maps of human centromeres. Science, 376(6588), Article eabl4178. https://doi.org/10.1126/science.abl4178

Altemose, N, Logsdon, GA, Bzikadze, AV, Sidhwani, P, Langley, SA, Caldas, GV, Hoyt, SJ, Uralsky, L, Ryabov, FD, Shew, CJ, Sauria, MEG, Borchers, M, Gershman, A, Mikheenko, A, Shepelev, VA, Dvorkina, T, Kunyavskaya, O, Vollger, MR, Rhie, A, McCartney, AM, Asri, M, Lorig-Roach, R, Shafin, K, Lucas, JK, Aganezov, S, Olson, D, de Lima, LG, Potapova, T, Hartley, GA, Haukness, M, Kerpedjiev, P, Gusev, F, Tigyi, K, Brooks, S, Young, A, Nurk, S, Koren, S, Salama, SR, Paten, B, Rogaev, EI, Streets, A, Karpen, GH, Dernburg, AF, Sullivan, BA, Straight, AF, Wheeler, TJ, Gerton, JL, Eichler, EE, Phillippy, AM, Timp, W, Dennis, MY, O'Neill, RJ, Zook, JM, Schatz, MC, Pevzner, PA, Diekhans, M, Langley, CH, Alexandrov, IA & Miga, KH 2022, 'Complete genomic and epigenetic maps of human centromeres', Science, vol. 376, no. 6588, eabl4178. https://doi.org/10.1126/science.abl4178

@article{4d260e9e52f74b67b7e590aaa55a5ae0,

title = "Complete genomic and epigenetic maps of human centromeres",

abstract = "Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, and functions, which include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere human genome assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric and centromeric repeats, which constitute 6.2% of the genome (189.9 megabases). Detailed maps of these regions revealed multimegabase structural rearrangements, including in active centromeric repeat arrays. Analysis of centromere-associated sequences uncovered a strong relationship between the position of the centromere and the evolution of the surrounding DNA through layered repeat expansions. Furthermore, comparisons of chromosome X centromeres across a diverse panel of individuals illuminated high degrees of structural, epigenetic, and sequence variation in these complex and rapidly evolving regions.",

author = "Nicolas Altemose and Logsdon, {Glennis A.} and Bzikadze, {Andrey V.} and Pragya Sidhwani and Langley, {Sasha A.} and Caldas, {Gina V.} and Hoyt, {Savannah J.} and Lev Uralsky and Ryabov, {Fedor D.} and Shew, {Colin J.} and Sauria, {Michael E.G.} and Matthew Borchers and Ariel Gershman and Alla Mikheenko and Shepelev, {Valery A.} and Tatiana Dvorkina and Olga Kunyavskaya and Vollger, {Mitchell R.} and Arang Rhie and McCartney, {Ann M.} and Mobin Asri and Ryan Lorig-Roach and Kishwar Shafin and Lucas, {Julian K.} and Sergey Aganezov and Daniel Olson and {de Lima}, {Leonardo Gomes} and Tamara Potapova and Hartley, {Gabrielle A.} and Marina Haukness and Peter Kerpedjiev and Fedor Gusev and Kristof Tigyi and Shelise Brooks and Alice Young and Sergey Nurk and Sergey Koren and Salama, {Sofie R.} and Benedict Paten and Rogaev, {Evgeny I.} and Aaron Streets and Karpen, {Gary H.} and Dernburg, {Abby F.} and Sullivan, {Beth A.} and Straight, {Aaron F.} and Wheeler, {Travis J.} and Gerton, {Jennifer L.} and Eichler, {Evan E.} and Phillippy, {Adam M.} and Winston Timp and Dennis, {Megan Y.} and O'Neill, {Rachel J.} and Zook, {Justin M.} and Schatz, {Michael C.} and Pevzner, {Pavel A.} and Mark Diekhans and Langley, {Charles H.} and Alexandrov, {Ivan A.} and Miga, {Karen H.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 The Authors",

year = "2022",

month = apr,

day = "1",

doi = "10.1126/science.abl4178",

language = "English (US)",

volume = "376",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6588",

}

TY - JOUR

T1 - Complete genomic and epigenetic maps of human centromeres

AU - Altemose, Nicolas

AU - Logsdon, Glennis A.

AU - Bzikadze, Andrey V.

AU - Sidhwani, Pragya

AU - Langley, Sasha A.

AU - Caldas, Gina V.

AU - Hoyt, Savannah J.

AU - Uralsky, Lev

AU - Ryabov, Fedor D.

AU - Shew, Colin J.

AU - Sauria, Michael E.G.

AU - Borchers, Matthew

AU - Gershman, Ariel

AU - Mikheenko, Alla

AU - Shepelev, Valery A.

AU - Dvorkina, Tatiana

AU - Kunyavskaya, Olga

AU - Vollger, Mitchell R.

AU - Rhie, Arang

AU - McCartney, Ann M.

AU - Asri, Mobin

AU - Lorig-Roach, Ryan

AU - Shafin, Kishwar

AU - Lucas, Julian K.

AU - Aganezov, Sergey

AU - Olson, Daniel

AU - de Lima, Leonardo Gomes

AU - Potapova, Tamara

AU - Hartley, Gabrielle A.

AU - Haukness, Marina

AU - Kerpedjiev, Peter

AU - Gusev, Fedor

AU - Tigyi, Kristof

AU - Brooks, Shelise

AU - Young, Alice

AU - Nurk, Sergey

AU - Koren, Sergey

AU - Salama, Sofie R.

AU - Paten, Benedict

AU - Rogaev, Evgeny I.

AU - Streets, Aaron

AU - Karpen, Gary H.

AU - Dernburg, Abby F.

AU - Sullivan, Beth A.

AU - Straight, Aaron F.

AU - Wheeler, Travis J.

AU - Gerton, Jennifer L.

AU - Eichler, Evan E.

AU - Phillippy, Adam M.

AU - Timp, Winston

AU - Dennis, Megan Y.

AU - O'Neill, Rachel J.

AU - Zook, Justin M.

AU - Schatz, Michael C.

AU - Pevzner, Pavel A.

AU - Diekhans, Mark

AU - Langley, Charles H.

AU - Alexandrov, Ivan A.

AU - Miga, Karen H.

PY - 2022/4/1

Y1 - 2022/4/1

N2 - Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, and functions, which include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere human genome assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric and centromeric repeats, which constitute 6.2% of the genome (189.9 megabases). Detailed maps of these regions revealed multimegabase structural rearrangements, including in active centromeric repeat arrays. Analysis of centromere-associated sequences uncovered a strong relationship between the position of the centromere and the evolution of the surrounding DNA through layered repeat expansions. Furthermore, comparisons of chromosome X centromeres across a diverse panel of individuals illuminated high degrees of structural, epigenetic, and sequence variation in these complex and rapidly evolving regions.

AB - Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, and functions, which include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere human genome assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric and centromeric repeats, which constitute 6.2% of the genome (189.9 megabases). Detailed maps of these regions revealed multimegabase structural rearrangements, including in active centromeric repeat arrays. Analysis of centromere-associated sequences uncovered a strong relationship between the position of the centromere and the evolution of the surrounding DNA through layered repeat expansions. Furthermore, comparisons of chromosome X centromeres across a diverse panel of individuals illuminated high degrees of structural, epigenetic, and sequence variation in these complex and rapidly evolving regions.

UR - http://www.scopus.com/inward/record.url?scp=85127420501&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85127420501&partnerID=8YFLogxK

U2 - 10.1126/science.abl4178

DO - 10.1126/science.abl4178

M3 - Article

C2 - 35357911

AN - SCOPUS:85127420501

SN - 0036-8075

VL - 376

JO - Science

JF - Science

IS - 6588

M1 - eabl4178

ER -

Complete genomic and epigenetic maps of human centromeres

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this