Copy number variants and fixed duplications among 198 rhesus macaques (Macaca mulatta)

Autoři: Marina Brasó-Vives aff001;  Inna S. Povolotskaya aff004;  Diego A. Hartasánchez aff001;  Xavier Farré aff001;  Marcos Fernandez-Callejo aff005;  Muthuswamy Raveendran aff006;  R. Alan Harris aff006;  Douglas L. Rosene aff008;  Belen Lorente-Galdos aff009;  Arcadi Navarro aff001;  Tomas Marques-Bonet aff001;  Jeffrey Rogers aff006;  David Juan aff001;  Inna S. Povolotskaya aff003;  Marcos Fernandez-Callejo aff004;  Muthuswamy Raveendran aff005;  R. Alan Harris aff005;  Douglas L. Rosene aff007;  Belen Lorente-Galdos aff008;  Jeffrey Rogers aff005
Působiště autorů: Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Parc de Recerca Biomèdica de Barcelona, Barcelona, Catalonia, Spain aff001;  Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain aff002;  Laboratoire de Biométrie et Biologie Évolutive UMR 5558, Université de Lyon, Université Lyon 1, CNRS, Villeurbanne, France aff002;  Laboratoire de Biométrie et Biologie Évolutive UMR 5558, Université de Lyon, Université Lyon 1, CNRS, Villeurbanne, France aff003;  Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Moscow, Russia aff003;  Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Moscow, Russia aff004;  National Centre for Genomic Analysis-Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain aff004;  National Centre for Genomic Analysis-Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain aff005;  Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States of America aff005;  Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States of America aff006;  Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America aff006;  Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America aff007;  Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, United States of America aff007;  Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts, United States of America aff008;  Department of Neuroscience, Yale School of Medicine, New Haven, Connecticut, United States of America aff008;  Department of Neuroscience, Yale School of Medicine, New Haven, Connecticut, United States of America aff009;  National Institute for Bioinformatics (INB), Barcelona, Catalonia, Spain aff009;  National Institute for Bioinformatics (INB), Barcelona, Catalonia, Spain aff010;  Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain aff010;  Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain aff011;  Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Catalonia, Spain aff011;  Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Catalonia, Spain aff012
Vyšlo v časopise: Copy number variants and fixed duplications among 198 rhesus macaques (Macaca mulatta). PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008742
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008742


The rhesus macaque is an abundant species of Old World monkeys and a valuable model organism for biomedical research due to its close phylogenetic relationship to humans. Copy number variation is one of the main sources of genomic diversity within and between species and a widely recognized cause of inter-individual differences in disease risk. However, copy number differences among rhesus macaques and between the human and macaque genomes, as well as the relevance of this diversity to research involving this nonhuman primate, remain understudied. Here we present a high-resolution map of sequence copy number for the rhesus macaque genome constructed from a dataset of 198 individuals. Our results show that about one-eighth of the rhesus macaque reference genome is composed of recently duplicated regions, either copy number variable regions or fixed duplications. Comparison with human genomic copy number maps based on previously published data shows that, despite overall similarities in the genome-wide distribution of these regions, there are specific differences at the chromosome level. Some of these create differences in the copy number profile between human disease genes and their rhesus macaque orthologs. Our results highlight the importance of addressing the number of copies of target genes in the design of experiments and cautions against human-centered assumptions in research conducted with model organisms. Overall, we present a genome-wide copy number map from a large sample of rhesus macaque individuals representing an important novel contribution concerning the evolution of copy number in primate genomes.

Klíčová slova:

Comparative genomics – Copy number variation – Genome-wide association studies – Human genomics – Macaque – Mammalian genomics – Primates – Rhesus monkeys


1. Keeney JG, Davis JM, Siegenthaler J, Post MD, Nielsen BS, Hopkins WD, et al. DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates. Brain Struct Funct. 2015;220: 3053–3060. doi: 10.1007/s00429-014-0814-9 24957859

2. Pouw RB, Brouwer MC, Geissler J, van Herpen LV, Zeerleder SS, Wuillemin WA, et al. Complement Factor H-Related Protein 3 Serum Levels Are Low Compared to Factor H and Mainly Determined by Gene Copy Number Variation in CFHR3. PLOS ONE. 2016;11: e0152164. doi: 10.1371/journal.pone.0152164 27007437

3. Bekpen C, Künzel S, Xie C, Eaaswarkhanth M, Lin YL, Gokcumen O, et al. Segmental duplications and evolutionary acquisition of UV damage response in the SPATA31 gene family of primates and humans. BMC Genomics. 2017;18: 1–12. doi: 10.1186/s12864-016-3406-7

4. Kondrashov F. Gene duplication as a mechanism of genomic adaptation to a changing environment. Proceedings of the Royal Society B: Biological Sciences. 2012; 5048–5057. doi: 10.1098/rspb.2012.1108 22977152

5. Sudmant PH, Huddleston J, Catacchio CR, Malig M, Hillier LW, Baker C, et al. Evolution and diversity of copy number variation in the great ape lineage. Genome Res. 2013;23: 1373–1382. doi: 10.1101/gr.158543.113 23825009

6. Dennis MY, Harshman L, Nelson BJ, Penn O, Cantsilieris S, Huddleston J, et al. The evolution and population diversity of human-specific segmental duplications. Nature Ecology and Evolution. 2017;1: 69. doi: 10.1038/s41559-016-0069 28580430

7. Kronenberg ZN, Fiddes IT, Gordon D, Murali S, Cantsilieris S, Meyerson OS, et al. High-resolution comparative analysis of great ape genomes. Science. 2018;360: aar6343.

8. Gokcumen O, Tischler V, Tica J, Zhu Q, Iskow RC, Lee E, et al. Primate genome architecture influences structural variation mechanisms and functional consequences. Proc Natl Acad Sci U S A. 2013;110: 15764–15769. doi: 10.1073/pnas.1305904110 24014587

9. Zimin AV, Cornish AS, Maudhoo MD, Gibbs RM, Zhang X, Pandey S, et al. A new rhesus macaque assembly and annotation for next-generation sequencing analyses. Biol Direct. 2014;9: 20. doi: 10.1186/1745-6150-9-20 25319552

10. Sato K, Kuroki Y, Kumita W, Fujiyama A, Toyoda A, Kawai J, et al. Resequencing of the common marmoset genome improves genome assemblies and gene-coding sequence analysis. Sci Rep. 2015;5: 16894. doi: 10.1038/srep16894 26586576

11. Larsen PA, Harris RA, Liu Y, Murali SC, Campbell CR, Brown AD, et al. Hybrid de novo genome assembly and centromere characterization of the gray mouse lemur (Microcebus murinus). BMC Biol. 2017;15: 110. doi: 10.1186/s12915-017-0439-6 29145861

12. Rogers J, Raveendran M, Harris RA, Mailund T, Leppälä K, Athanasiadis G, et al. The comparative genomics and complex population history of Papio baboons. Science Advances. 2019;5. doi: 10.1126/sciadv.aau6947 30854422

13. Rigau M, Juan D, Valencia A, Rico D. Intronic CNVs and gene expression variation in human populations. PLoS Genet. 2019;15: e1007902. doi: 10.1371/journal.pgen.1007902 30677042

14. Stankiewicz P, Lupski J. Structural variation in the human genome and its role in disease. Annu Rev Med. 2010;61: 437–455. doi: 10.1146/annurev-med-100708-204735 20059347

15. Shishido E, Aleksic B, Ozaki N. Copy-number variation in the pathogenesis of autism spectrum disorder. Psychiatry and Clinical Neurosciences. 2014;68: 85–95. doi: 10.1111/pcn.12128 24372918

16. Neira-Fresneda J, Potocki L. Neurodevelopmental Disorders Associated with Abnormal Gene Dosage: Smith–Magenis and Potocki–Lupski Syndromes. Journal of Pediatric Genetics. 2015;04: 159–167.

17. Leu C, Coppola A, Sisodiya SM. Progress from genome-wide association studies and copy number variant studies in epilepsy. Curr Opin Neurol. 2016;29: 158–167. doi: 10.1097/WCO.0000000000000296 26886358

18. Hollox EJ, Hoh B-P. Human gene copy number variation and infectious disease. Human Genetics. 2014;133: 1217–1233. doi: 10.1007/s00439-014-1457-x 25110110

19. Liedigk R, Roos C, Brameier M, Zinner D. Mitogenomics of the Old World monkey tribe Papionini. BMC Evol Biol. 2014;14: 176. doi: 10.1186/s12862-014-0176-1 25209564

20. Phillips KA, Bales KL, Capitanio JP, Conley A, Czoty PW, ‘t Hart BA, et al. Why primate models matter. American Journal of Primatology. 2014;76: 801–827. doi: 10.1002/ajp.22281 24723482

21. Peters A, Kemper T. A review of the structural alterations in the cerebral hemispheres of the aging rhesus monkey. Neurobiol Aging. 2012;33: 2357–2372. doi: 10.1016/j.neurobiolaging.2011.11.015 22192242

22. Rogers J, Raveendran M, Fawcett GL, Fox AS, Shelton SE, Oler JA, et al. CRHR1 genotypes, neural circuits and the diathesis for anxiety and depression. Mol Psychiatry. 2013;18: 700. doi: 10.1038/mp.2012.152 23147386

23. Bauman MD, Schumann CM. Advances in nonhuman primate models of autism: Integrating neuroscience and behavior. Exp Neurol. 2018;299: 252–265. doi: 10.1016/j.expneurol.2017.07.021 28774750

24. Janssen P, Verhoef B-E, Premereur E. Functional interactions between the macaque dorsal and ventral visual pathways during three-dimensional object vision. Cortex. 2018;98: 218–227. doi: 10.1016/j.cortex.2017.01.021 28258716

25. Bakken TE, Miller JA, Ding S-L, Sunkin SM, Smith KA, Ng L, et al. A comprehensive transcriptional map of primate brain development. Nature. 2016;535: 367–375. doi: 10.1038/nature18637 27409810

26. Loffredo JT, Friedrich TC, León EJ, Stephany JJ, Rodrigues DS, Spencer SP, et al. CD8+ T cells from SIV elite controller macaques recognize Mamu-B*08-bound epitopes and select for widespread viral variation. PLoS One. 2007;2: e1152. doi: 10.1371/journal.pone.0001152 18000532

27. Hansen SG, Piatak M Jr, Ventura AB, Hughes CM, Gilbride RM, Ford JC, et al. Immune clearance of highly pathogenic SIV infection. Nature. 2013;502: 100–104. doi: 10.1038/nature12519 24025770

28. Sandler NG, Bosinger SE, Estes JD, Zhu RTR, Tharp GK, Boritz E, et al. Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature. 2014;511: 601–605. doi: 10.1038/nature13554 25043006

29. Kuroda MJ, Sugimoto C, Cai Y, Merino KM, Mehra S, Araínga M, et al. High Turnover of Tissue Macrophages Contributes to Tuberculosis Reactivation in Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Infect Dis. 2018;217: 1865–1874. doi: 10.1093/infdis/jix625 29432596

30. Groves C. Primate Taxonomy. Smithsonian Institution Press, Washington, DC; 2001.

31. Xue C, Raveendran M, Harris RA, Fawcett GL, Liu X, White S, et al. The population genomics of rhesus macaques (Macaca mulatta) based on whole genome sequences. Genome Res. 2016;26: 1651–1662. doi: 10.1101/gr.204255.116 27934697

32. Bimber BN, Ramakrishnan R, Cervera-Juanes R, Madhira R, Peterson SM, Norgren RB, et al. Whole genome sequencing predicts novel human disease models in rhesus macaques. Genomics. 2017;109: 214–220. doi: 10.1016/j.ygeno.2017.04.001 28438488

33. Marques-Bonet T, Eichler EE. The evolution of human segmental duplications and the core duplicon hypothesis. Cold Spring Harb Symp Quant Biol. 2009;74: 355–362. doi: 10.1101/sqb.2009.74.011 19717539

34. Lorente-Galdos B, Bleyhl J, Santpere G, Vives L, Ramírez O, Hernandez J, et al. Accelerated exon evolution within primate segmental duplications. Genome Biol. 2013;14: R9. doi: 10.1186/gb-2013-14-1-r9 23360670

35. Marques-Bonet T, Girirajan S, Eichler EE. The origins and impact of primate segmental duplications. Trends in Genetics. 2009. pp. 443–454. doi: 10.1016/j.tig.2009.08.002 19796838

36. Lee AS, Gutiérrez-Arcelus M, Perry GH, Vallender EJ, Johnson WE, Miller GM, et al. Analysis of copy number variation in the rhesus macaque genome identifies candidate loci for evolutionary and human disease studies. Hum Mol Genet. 2008;17: 1127–1136. doi: 10.1093/hmg/ddn002 18180252

37. Degenhardt JD, De Candia P, Chabot A, Schwartz S, Henderson L, Ling B, et al. Copy number variation of CCL3-like genes affects rate of progression to simian-AIDS in rhesus macaques (Macaca mulatta). PLoS Genet. 2009;5. doi: 10.1371/journal.pgen.1000346 19165326

38. Hellmann I, Lim SY, Gelman RS, Letvin NL. Association of activating KIR copy number variation of NK cells with containment of SIV replication in rhesus monkeys. PLoS Pathog. 2011;7: 1–12.

39. Hellmann I, Schmitz JE, Letvin NL. Activating KIR Copy Number Variation Is Associated with Granzyme B Release by NK Cells during Primary Simian Immunodeficiency Virus Infection in Rhesus Monkeys. J Virol. 2012;86: 13103–13107. doi: 10.1128/JVI.00325-12 23015705

40. Hellmann I, Letvin NL, Schmitz JE. KIR2DL4 Copy Number Variation Is Associated with CD4+ T-Cell Depletion and Function of Cytokine-Producing NK Cell Subsets in SIV-Infected Mamu-A*01-Negative Rhesus Macaques. J Virol. 2013;87: 5305–5310. doi: 10.1128/JVI.02949-12 23449795

41. Ottolini B, Hornsby MJ, Abujaber R, MacArthur JAL, Badge RM, Schwarzacher T, et al. Evidence of convergent evolution in humans and macaques supports an adaptive role for copy number variation of the β-defensin-2 gene. Genome Biol Evol. 2014;6: 3025–3038. doi: 10.1093/gbe/evu236 25349268

42. de Groot NG, Blokhuis JH, Otting N, Doxiadis GGM, Bontrop RE. Co-evolution of the MHC class I and KIR gene families in rhesus macaques: Ancestry and plasticity. Immunol Rev. 2015;267: 228–245. doi: 10.1111/imr.12313 26284481

43. Serres-Armero A, Povolotskaya IS, Quilez J, Ramirez O, Santpere G, Kuderna LFK, et al. Similar genomic proportions of copy number variation within gray wolves and modern dog breeds inferred from whole genome sequencing. BMC Genomics. 2017;18: 1–15. doi: 10.1186/s12864-016-3406-7

44. Dobrynin P, Liu S, Tamazian G, Xiong Z, Yurchenko AA, Krasheninnikova K, et al. Genomic legacy of the African cheetah, Acinonyx jubatus. Genome Biol. 2015;16: 277. doi: 10.1186/s13059-015-0837-4 26653294

45. Warren WC, Kuderna L, Alexander A, Catchen J, Pérez-Silva JG, López-Otín C, et al. The Novel Evolution of the Sperm Whale Genome. Genome Biol Evol. 2017;9: 3260–3264. doi: 10.1093/gbe/evx187 28985367

46. Librado P, Gamba C, Gaunitz C, Der Sarkissian C, Pruvost M, Albrechtsen A, et al. Ancient genomic changes associated with domestication of the horse. Science. 2017;356: 442–445. doi: 10.1126/science.aam5298 28450643

47. Tollis M, Robbins J, Webb AE, Kuderna LFK, Caulin AF, Garcia JD, et al. Return to the Sea, Get Huge, Beat Cancer: An Analysis of Cetacean Genomes Including an Assembly for the Humpback Whale (Megaptera novaeangliae). Mol Biol Evol. 2019;36: 1746–1763. doi: 10.1093/molbev/msz099 31070747

48. Alkan C, Kidd JM, Marques-Bonet T, Aksay G, Antonacci F, Hormozdiari F, et al. Personalized copy number and segmental duplication maps using next-generation sequencing. Nat Genet. 2009;41: 1061–1067. doi: 10.1038/ng.437 19718026

49. Bailey JA, Gu Z, Clark RA, Reinert K, Samonte RV, Schwartz S, et al. Recent segmental duplications in the human genome. Science. 2002;297: 1003–1007. doi: 10.1126/science.1072047 12169732

50. Hartasánchez DA, Brasó-Vives M, Heredia-Genestar JM, Pybus M, Navarro A. Effect of collapsed duplications on diversity estimates: what to expect. Genome Biol Evol. 2018;10: 2899–2905. doi: 10.1093/gbe/evy223 30364947

51. Mallick S, Li H, Lipson M, Mathieson I, Gymrek M, Racimo F, et al. The Simons Genome Diversity Project: 300 genomes from 142 diverse populations. Nature. 2016;538: 201–206. doi: 10.1038/nature18964 27654912

52. She X, Horvath JE, Jiang Z, Liu G, Furey TS, Christ L, et al. The structure and evolution of centromeric transition regions within the human genome. Nature. 2004;430: 857–864. doi: 10.1038/nature02806 15318213

53. Bailey JA, Eichler EE. Primate segmental duplications: crucibles of evolution, diversity and disease. Nat Rev Genet. 2006;7: 552–564. 16770338

54. Jiang Z, Tang H, Ventura M, Cardone MF, Marques-Bonet T, She X, et al. Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution. Nat Genet. 2007;39: 1361–1368. doi: 10.1038/ng.2007.9 17922013

55. Karolchik D, Hinrichs AS, Furey TS, Roskin KM, Sugnet CW, Haussler D, et al. The UCSC Table Browser data retrieval tool. Nucleic Acids Res. 2004;32: D493–6. doi: 10.1093/nar/gkh103 14681465

56. Juan D, Rico D, Marques-Bonet T, Fernandez-Capetillo O, Valencia A. Late-replicating CNVs as a source of new genes. Biol Open. 2013;2: 1402–1411. doi: 10.1242/bio.20136924 24285712

57. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, et al. The DNA sequence and biology of human chromosome 19. Nature. 2004;428: 529–535. doi: 10.1038/nature02399 15057824

58. Kim PM, Lam HYK, Urban AE, Korbel JO, Affourtit J, Grubert F, et al. Analysis of copy number variants and segmental duplications in the human genome: Evidence for a change in the process of formation in recent evolutionary history. Genome Res. 2008;18: 1865–1874. doi: 10.1101/gr.081422.108 18842824

59. Iskow RC, Gokcumen O, Lee C. Exploring the role of copy number variants in human adaptation. Trends Genet. 2012;28: 245–257. doi: 10.1016/j.tig.2012.03.002 22483647

60. Zerbino DR, Achuthan P, Akanni W, Amode MR, Barrell D, Bhai J, et al. Ensembl 2018. Nucleic Acids Res. 2018;46: D754–D761. doi: 10.1093/nar/gkx1098 29155950

61. Ezkurdia I, Juan D, Rodriguez JM, Frankish A, Diekhans M, Harrow J, et al. Multiple evidence strands suggest that there may be as few as 19 000 human protein-coding genes. Hum Mol Genet. 2014;23: 5866–5878. doi: 10.1093/hmg/ddu309 24939910

62. Abascal F, Juan D, Jungreis I, Martinez L, Rigau M, Rodriguez JM, et al. Loose ends: almost one in five human genes still have unresolved coding status. Nucleic Acids Res. 2018;46: 7070–7084. doi: 10.1093/nar/gky587 29982784

63. Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, et al. An integrated map of structural variation in 2,504 human genomes. Nature. 2015;526: 75–81. doi: 10.1038/nature15394 26432246

64. MacArthur J, Bowler E, Cerezo M, Gil L, Hall P, Hastings E, et al. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res. 2017;45: D896–D901. doi: 10.1093/nar/gkw1133 27899670

65. Piñero J, Bravo À, Queralt-Rosinach N, Gutiérrez-Sacristán A, Deu-Pons J, Centeno E, et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. 2017;45: D833–D839. doi: 10.1093/nar/gkw943 27924018

66. Alison M, Heron EA, Hughes G, McGrath J, Tansey K, Gallagher L, et al. A genome-wide scan for common alleles affecting risk for autism. Hum Mol Genet. 2010;19: 4072–4082. doi: 10.1093/hmg/ddq307 20663923

67. Zou M, Li S, Klein WH, Xiang M. Brn3a/Pou4f1 regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord. Dev Biol. 2012;364: 114–127. doi: 10.1016/j.ydbio.2012.01.021 22326227

68. Furney SJ, Simmons A, Breen G, Pedroso I, Lunnon K, Proitsi P, et al. Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer’s disease. Mol Psychiatry. 2011;16: 1130–1138. doi: 10.1038/mp.2010.123 21116278

69. Lanni C, Nardinocchi L, Puca R, Stanga S, Uberti D, Memo M, et al. Homeodomain interacting protein kinase 2: a target for Alzheimer’s beta amyloid leading to misfolded p53 and inappropriate cell survival. PLoS One. 2010;5: e10171. doi: 10.1371/journal.pone.0010171 20418953

70. Wiggins AK, Wei G, Doxakis E, Wong C, Tang AA, Zang K, et al. Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival. J Cell Biol. 2004;167: 257–267. doi: 10.1083/jcb.200406131 15492043

71. Salyakina D, Cukier HN, Lee JM, Sacharow S, Nations LD, Ma D, et al. Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk. PLoS One. 2011;6: e26049. doi: 10.1371/journal.pone.0026049 22016809

72. Miyamoto T, Hasuike S, Yogev L, Maduro MR, Ishikawa M, Westphal H, et al. Azoospermia in patients heterozygous for a mutation in SYCP3. The Lancet. 2003;362: 1714–1719.

73. Bollschweiler D, Radu L, Joudeh L, Plitzko JM, Henderson RM, Mela I, et al. Molecular architecture of the SYCP3 fibre and its interaction with DNA. Open Biol. 2019;9: 190094. doi: 10.1098/rsob.190094 31615332

74. Richard AF, Goldstein SJ, Dewar RE. Weed macaques: The evolutionary implications of macaque feeding ecology. Int J Primatol. 1989;10: 569–594.

75. Stratonovich RL. Conditional Markov Processes. Theory Probab Appl. 1960;5: 156–178.

76. Smit AFA. The origin of interspersed repeats in the human genome. Current Opinion in Genetics & Development. 1996;6: 743–748.

77. Benson G. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res. 1999;27: 573–580. doi: 10.1093/nar/27.2.573 9862982

78. Marco-Sola S, Sammeth M, Guigó R, Ribeca P. The GEM mapper: fast, accurate and versatile alignment by filtration. Nat Methods. 2012;9: 1185–1188. doi: 10.1038/nmeth.2221 23103880

79. Rabiner LR. A tutorial on hidden Markov models and selected applications in speech recognition. Proc IEEE. 1989;77: 257–286.

80. Bayes FRSLRM. LII. An essay towards solving a problem in the doctrine of chances. By the late Rev. Mr. Bayes, F. R. S. communicated by Mr. Price, in a letter to John Canton, A. M. F. R. S. Philosophical Transactions. 1763;53: 370–418.

81. Abel HJ, Duncavage E. Detection of structural DNA variation from next generation sequencing data: a review of informatic approaches. Cancer Genet. 2013;206: 432–440. doi: 10.1016/j.cancergen.2013.11.002 24405614

82. Massey FJ Jr. The Kolmogorov-Smirnov Test for Goodness of Fit. J Am Stat Assoc. 1951;46: 68–78.

83. Pearson K. Notes on regression and inheritance in the case of two parents. Proc R Soc Lond. 1895;58: 240–242.

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