Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility
Wesley C. Warren, R. Alan Harris, Marina Haukness, Ian T. Fiddes, Shwetha C. Murali, Jason D. Fernandes, Philip C. Dishuck, Jessica M. Storer, Muthuswamy Raveendran, LaDeana Hillier, David Porubskỳ, Yafei Mao, David Gordon, Mitchell R. Vollger, Alexandra P. Lewis, Katherine M. Munson, Elizabeth DeVogelaere, Joel Armstrong, Mark Diekhans, Jerilyn A. Walker, Chad Tomlinson, Tina A. Graves-Lindsay, Milinn Kremitzki, Sofie R. Salama, Peter A. Audano, Merly Escalona, Nicholas Maurer, Francesca Antonacci, Ludovica Mercuri, Flavia Angela Maria Maggiolini, Claudia Rita Catacchio, Jason G. Underwood, David H. O’Connor, Ashley D. Sanders, Jan O. Korbel, Betsy Ferguson, H. Michael Kubisch, Louis J. Picker, Ned H. Kalin, Douglas L. Rosene, Jon E. Levine, David H. Abbott, Stanton B. Gray, Mar M. Sánchez, Zsofia A. Kovacs-Balint, Joseph W. Kemnitz, Sara M. Thomasy, Jeffrey A. Roberts, Erin L. Kinnally, John P. Capitanio, J. H. Pate Skene, Michael L. Platt, Shelley A. Cole, Richard E. Green, Mario Ventura, Roger W. Wiseman, Benedict Paten, Mark A. Batzer, Jeffrey Rogers, Evan E. Eichler
Abstract
) 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.