Browsing by Author "Porubsky, David"
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Item Open Access Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility.(Science (New York, N.Y.), 2020-12) Warren, Wesley C; Harris, R Alan; Haukness, Marina; Fiddes, Ian T; Murali, Shwetha C; Fernandes, Jason; Fernandes, Jason; Dishuck, Philip C; Storer, Jessica M; Raveendran, Muthuswamy; Hillier, LaDeana W; Porubsky, David; Mao, Yafei; Gordon, David; Vollger, Mitchell R; Lewis, Alexandra P; Munson, Katherine M; DeVogelaere, Elizabeth; Armstrong, Joel; Diekhans, Mark; Walker, Jerilyn A; Tomlinson, Chad; Graves-Lindsay, Tina A; Kremitzki, Milinn; Salama, Sofie R; Audano, Peter A; Escalona, Merly; Maurer, Nicholas W; Antonacci, Francesca; Mercuri, Ludovica; Maggiolini, Flavia AM; Catacchio, Claudia Rita; Underwood, Jason G; O'Connor, David H; Sanders, Ashley D; Korbel, Jan O; Ferguson, Betsy; Kubisch, H Michael; Picker, Louis; Kalin, Ned H; Rosene, Douglas; Levine, Jon; Abbott, David H; Gray, Stanton B; Sanchez, Mar M; Kovacs-Balint, Zsofia A; Kemnitz, Joseph W; Thomasy, Sara M; Roberts, Jeffrey A; Kinnally, Erin L; Capitanio, John P; Skene, JH Pate; Platt, Michael; Cole, Shelley A; Green, Richard E; Ventura, Mario; Wiseman, Roger W; Paten, Benedict; Batzer, Mark A; Rogers, Jeffrey; Eichler, Evan EThe rhesus macaque (Macaca mulatta) is the most widely studied nonhuman primate (NHP) in biomedical research. We present an updated reference genome assembly (Mmul_10, contig N50 = 46 Mbp) that increases the sequence contiguity 120-fold and annotate it using 6.5 million full-length transcripts, thus improving our understanding of gene content, isoform diversity, and repeat organization. With the improved assembly of segmental duplications, we discovered new lineage-specific genes and expanded gene families that are potentially informative in studies of evolution and disease susceptibility. Whole-genome sequencing (WGS) data from 853 rhesus macaques identified 85.7 million single-nucleotide variants (SNVs) and 10.5 million indel variants, including potentially damaging variants in genes associated with human autism and developmental delay, providing a framework for developing noninvasive NHP models of human disease.Item Open Access Telomere-to-telomere assembly of a complete human X chromosome.(Nature, 2020-09) Miga, Karen H; Koren, Sergey; Rhie, Arang; Vollger, Mitchell R; Gershman, Ariel; Bzikadze, Andrey; Brooks, Shelise; Howe, Edmund; Porubsky, David; Logsdon, Glennis A; Schneider, Valerie A; Potapova, Tamara; Wood, Jonathan; Chow, William; Armstrong, Joel; Fredrickson, Jeanne; Pak, Evgenia; Tigyi, Kristof; Kremitzki, Milinn; Markovic, Christopher; Maduro, Valerie; Dutra, Amalia; Bouffard, Gerard G; Chang, Alexander M; Hansen, Nancy F; Wilfert, Amy B; Thibaud-Nissen, Françoise; Schmitt, Anthony D; Belton, Jon-Matthew; Selvaraj, Siddarth; Dennis, Megan Y; Soto, Daniela C; Sahasrabudhe, Ruta; Kaya, Gulhan; Quick, Josh; Loman, Nicholas J; Holmes, Nadine; Loose, Matthew; Surti, Urvashi; Risques, Rosa Ana; Graves Lindsay, Tina A; Fulton, Robert; Hall, Ira; Paten, Benedict; Howe, Kerstin; Timp, Winston; Young, Alice; Mullikin, James C; Pevzner, Pavel A; Gerton, Jennifer L; Sullivan, Beth A; Eichler, Evan E; Phillippy, Adam MAfter two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end to end, and hundreds of unresolved gaps persist1,2. Here we present a human genome assembly that surpasses the continuity of GRCh382, along with a gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome3, we reconstructed the centromeric satellite DNA array (approximately 3.1 Mb) and closed the 29 remaining gaps in the current reference, including new sequences from the human pseudoautosomal regions and from cancer-testis ampliconic gene families (CT-X and GAGE). These sequences will be integrated into future human reference genome releases. In addition, the complete chromosome X, combined with the ultra-long nanopore data, allowed us to map methylation patterns across complex tandem repeats and satellite arrays. Our results demonstrate that finishing the entire human genome is now within reach, and the data presented here will facilitate ongoing efforts to complete the other human chromosomes.