000303081 001__ 303081 000303081 005__ 20250827124026.0 000303081 0247_ $$2doi$$a10.1038/s41586-025-09140-6 000303081 0247_ $$2pmid$$apmid:40702183 000303081 0247_ $$2ISSN$$a0028-0836 000303081 0247_ $$2ISSN$$a1476-4687 000303081 0247_ $$2altmetric$$aaltmetric:179576794 000303081 037__ $$aDKFZ-2025-01506 000303081 041__ $$aEnglish 000303081 082__ $$a500 000303081 1001_ $$00000-0003-2396-0656$$aLogsdon, Glennis A$$b0 000303081 245__ $$aComplex genetic variation in nearly complete human genomes. 000303081 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2025 000303081 3367_ $$2DRIVER$$aarticle 000303081 3367_ $$2DataCite$$aOutput Types/Journal article 000303081 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1756291170_16150 000303081 3367_ $$2BibTeX$$aARTICLE 000303081 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000303081 3367_ $$00$$2EndNote$$aJournal Article 000303081 500__ $$aDivision of Computational Genomics and Systems Genetics, German Cancer Research Center, Heidelberg, Germany. / 2025 Aug;644(8076):430-441 000303081 520__ $$aDiverse sets of complete human genomes are required to construct a pangenome reference and to understand the extent of complex structural variation. Here we sequence 65 diverse human genomes and build 130 haplotype-resolved assemblies (median continuity of 130 Mb), closing 92% of all previous assembly gaps1,2 and reaching telomere-to-telomere status for 39% of the chromosomes. We highlight complete sequence continuity of complex loci, including the major histocompatibility complex (MHC), SMN1/SMN2, NBPF8 and AMY1/AMY2, and fully resolve 1,852 complex structural variants. In addition, we completely assemble and validate 1,246 human centromeres. We find up to 30-fold variation in α-satellite higher-order repeat array length and characterize the pattern of mobile element insertions into α-satellite higher-order repeat arrays. Although most centromeres predict a single site of kinetochore attachment, epigenetic analysis suggests the presence of two hypomethylated regions for 7% of centromeres. Combining our data with the draft pangenome reference1 significantly enhances genotyping accuracy from short-read data, enabling whole-genome inference3 to a median quality value of 45. Using this approach, 26,115 structural variants per individual are detected, substantially increasing the number of structural variants now amenable to downstream disease association studies. 000303081 536__ $$0G:(DE-HGF)POF4-312$$a312 - Funktionelle und strukturelle Genomforschung (POF4-312)$$cPOF4-312$$fPOF IV$$x0 000303081 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000303081 7001_ $$00000-0001-7441-532X$$aEbert, Peter$$b1 000303081 7001_ $$00000-0002-5187-0415$$aAudano, Peter A$$b2 000303081 7001_ $$00000-0002-6279-6855$$aLoftus, Mark$$b3 000303081 7001_ $$00000-0001-8414-8966$$aPorubsky, David$$b4 000303081 7001_ $$aEbler, Jana$$b5 000303081 7001_ $$00000-0001-8795-5800$$aYilmaz, Feyza$$b6 000303081 7001_ $$00000-0002-0588-3987$$aHallast, Pille$$b7 000303081 7001_ $$00000-0001-7469-6651$$aProdanov, Timofey$$b8 000303081 7001_ $$00000-0003-0033-3721$$aYoo, DongAhn$$b9 000303081 7001_ $$aPaisie, Carolyn A$$b10 000303081 7001_ $$aHarvey, William T$$b11 000303081 7001_ $$aZhao, Xuefang$$b12 000303081 7001_ $$aMartino, Gianni V$$b13 000303081 7001_ $$aHenglin, Mir$$b14 000303081 7001_ $$00000-0001-8413-6498$$aMunson, Katherine M$$b15 000303081 7001_ $$aRabbani, Keon$$b16 000303081 7001_ $$00000-0003-4394-2455$$aChin, Chen-Shan$$b17 000303081 7001_ $$aGu, Bida$$b18 000303081 7001_ $$aAshraf, Hufsah$$b19 000303081 7001_ $$aScholz, Stephan$$b20 000303081 7001_ $$aAustine-Orimoloye, Olanrewaju$$b21 000303081 7001_ $$aBalachandran, Parithi$$b22 000303081 7001_ $$0P:(DE-He78)ed3a2ed903bfbc6b0c33ef7009b141ce$$aBonder, Marc Jan$$b23 000303081 7001_ $$00000-0002-9209-5793$$aCheng, Haoyu$$b24 000303081 7001_ $$00000-0001-5750-1808$$aChong, Zechen$$b25 000303081 7001_ $$00000-0002-7286-5690$$aCrabtree, Jonathan$$b26 000303081 7001_ $$00000-0002-9746-3719$$aGerstein, Mark$$b27 000303081 7001_ $$aGuethlein, Lisbeth A$$b28 000303081 7001_ $$aHasenfeld, Patrick$$b29 000303081 7001_ $$00000-0002-2280-9404$$aHickey, Glenn$$b30 000303081 7001_ $$aHoekzema, Kendra$$b31 000303081 7001_ $$00000-0002-8350-1235$$aHunt, Sarah E$$b32 000303081 7001_ $$aJensen, Matthew$$b33 000303081 7001_ $$00000-0001-8768-0050$$aJiang, Yunzhe$$b34 000303081 7001_ $$00000-0002-1472-8962$$aKoren, Sergey$$b35 000303081 7001_ $$00000-0002-5024-2134$$aKwon, Youngjun$$b36 000303081 7001_ $$aLi, Chong$$b37 000303081 7001_ $$aLi, Heng$$b38 000303081 7001_ $$00000-0002-6796-335X$$aLi, Jiaqi$$b39 000303081 7001_ $$00000-0001-8370-7703$$aNorman, Paul J$$b40 000303081 7001_ $$aOshima, Keisuke K$$b41 000303081 7001_ $$00000-0001-8863-3539$$aPaten, Benedict$$b42 000303081 7001_ $$00000-0003-2983-8934$$aPhillippy, Adam M$$b43 000303081 7001_ $$00000-0003-0114-528X$$aPollock, Nicholas R$$b44 000303081 7001_ $$aRausch, Tobias$$b45 000303081 7001_ $$aRautiainen, Mikko$$b46 000303081 7001_ $$00000-0003-2537-4343$$aSong, Yuwei$$b47 000303081 7001_ $$aSöylev, Arda$$b48 000303081 7001_ $$aSulovari, Arvis$$b49 000303081 7001_ $$00000-0002-0575-7673$$aSurapaneni, Likhitha$$b50 000303081 7001_ $$aTsapalou, Vasiliki$$b51 000303081 7001_ $$00000-0003-4755-1072$$aZhou, Weichen$$b52 000303081 7001_ $$aZhou, Ying$$b53 000303081 7001_ $$aZhu, Qihui$$b54 000303081 7001_ $$00000-0001-6594-7199$$aZody, Michael C$$b55 000303081 7001_ $$00000-0003-3425-6998$$aMills, Ryan E$$b56 000303081 7001_ $$aDevine, Scott E$$b57 000303081 7001_ $$aShi, Xinghua$$b58 000303081 7001_ $$aTalkowski, Michael E$$b59 000303081 7001_ $$00000-0001-5395-1457$$aChaisson, Mark J P$$b60 000303081 7001_ $$aDilthey, Alexander T$$b61 000303081 7001_ $$00000-0002-3190-1667$$aKonkel, Miriam K$$b62 000303081 7001_ $$aKorbel, Jan O$$b63 000303081 7001_ $$00000-0001-7317-6662$$aLee, Charles$$b64 000303081 7001_ $$00000-0001-7821-8489$$aBeck, Christine R$$b65 000303081 7001_ $$00000-0002-8246-4014$$aEichler, Evan E$$b66 000303081 7001_ $$00000-0002-9376-1030$$aMarschall, Tobias$$b67 000303081 773__ $$0PERI:(DE-600)1413423-8$$a10.1038/s41586-025-09140-6$$n8076$$p430-441$$tNature$$v644$$x0028-0836$$y2025 000303081 909CO $$ooai:inrepo02.dkfz.de:303081$$pVDB 000303081 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)ed3a2ed903bfbc6b0c33ef7009b141ce$$aDeutsches Krebsforschungszentrum$$b23$$kDKFZ 000303081 9131_ $$0G:(DE-HGF)POF4-312$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunktionelle und strukturelle Genomforschung$$x0 000303081 9141_ $$y2025 000303081 915__ $$0StatID:(DE-HGF)3003$$2StatID$$aDEAL Nature$$d2025-01-06$$wger 000303081 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)1040$$2StatID$$aDBCoverage$$bZoological Record$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)1060$$2StatID$$aDBCoverage$$bCurrent Contents - Agriculture, Biology and Environmental Sciences$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)1200$$2StatID$$aDBCoverage$$bChemical Reactions$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)1210$$2StatID$$aDBCoverage$$bIndex Chemicus$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNATURE : 2022$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2025-01-06 000303081 915__ $$0StatID:(DE-HGF)9960$$2StatID$$aIF >= 60$$bNATURE : 2022$$d2025-01-06 000303081 9201_ $$0I:(DE-He78)B260-20160331$$kB260$$lB260 Bioinformatik der Genomik und Systemgenetik$$x0 000303081 980__ $$ajournal 000303081 980__ $$aVDB 000303081 980__ $$aI:(DE-He78)B260-20160331 000303081 980__ $$aUNRESTRICTED