Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility

Warren W. C.; Harris R. A.; Haukness M.; Fiddes I. T.; Murali S. C.; Fernandes J.; Dishuck P. C.; Storer J. M.; Raveendran M.; Hillier L. W.; Porubsky D.; Mao Y.; Gordon D.; Vollger M. R.; Lewis A. P.; Munson K. M.; DeVogelaere E.; Armstrong J.; Diekhans M.; Walker J. A.; Tomlinson C.; Graves-Lindsay T. A.; Kremitzki M.; Salama S. R.; Audano P. A.; Escalona M.; Maurer N. W.; Antonacci F.; Mercuri L.; Maggiolini F. A. M.; Catacchio C. R.; Underwood J. G.; O'Connor D. H.; Sanders A. D.; Korbel J. O.; Ferguson B.; Kubisch H. M.; Picker L.; Kalin N. H.; Rosene D.; Levine J.; Abbott D. H.; Gray S. B.; Sanchez M. M.; Kovacs-Balint Z. A.; Kemnitz J. W.; Thomasy S. M.; Roberts J. A.; Kinnally E. L.; Capitanio J. P.; Skene J. H. P.; Platt M.; Cole S. A.; Green R. E.; Ventura M.; Wiseman R. W.; Paten B.; Batzer M. A.; Rogers J.; Eichler E. E.

doi:10.1126/science.abc6617

The 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.