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Transposable element-mediated structural variation analysis in dog breeds using whole-genome sequencing

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Abstract

Naturally occurring diseases in dogs provide an important animal model for studying human disease including cancer, heart disease, and autoimmune disorders. Transposable elements (TEs) make up ~ 31% of the dog (Canis lupus familiaris) genome and are one of main drivers to cause genomic variations and alter gene expression patterns of the host genes, which could result in genetic diseases. To detect structural variations (SVs), we conducted whole-genome sequencing of three different breeds, including Maltese, Poodle, and Yorkshire Terrier. Genomic SVs were detected and visualized using BreakDancer program. We identified a total of 2328 deletion SV events in the three breeds compared with the dog reference genome of Boxer. The majority of the genetic variants were found to be TE insertion polymorphism (1229) and the others were TE-mediated deletion (489), non-TE-mediated deletion (542), simple repeat-mediated deletion (32), and other indel (36). Among the TE insertion polymorphism, 286 elements were full-length LINE-1s (L1s). In addition, the 49 SV candidates located in the genic regions were experimentally verified and their polymorphic rates within each breed were examined using PCR assay. Polymorphism analysis of the genomic variants revealed that some of the variants exist polymorphic in the three dog breeds, suggesting that their SV events recently occurred in the dog genome. The findings suggest that TEs have contributed to the genomic variations among the three dog breeds of Maltese, Poodle, and Yorkshire Terrier. In addition, the polymorphic events between the dog breeds indicate that TEs were recently retrotransposed in the dog genome.

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Data availability

The whole-genome sequencing data have been deposited into NCBI Short Read Archive (SRA) under the project SRP159058.

References

  • Ayarpadikannan S, Kim HS (2014) The impact of transposable elements in genome evolution and genetic instability and their implications in various diseases. Genomics Inform 12:98–104

    PubMed  PubMed Central  Google Scholar 

  • Barrio AM, Ekerljung M, Jern P, Benachenhou F, Sperber GO, Bongcam-Rudloff E, Blomberg J, Andersson G (2011) The first sequenced carnivore genome shows complex host-endogenous retrovirus relationships. PLoS ONE 6:e19832

    CAS  PubMed  Google Scholar 

  • Beck CR, Garcia-Perez JL, Badge RM, Moran JV (2011) LINE-1 elements in structural variation and disease. Annu Rev Genomics Hum Genet 12:187–215

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bergman CM, Quesneville H (2007) Discovering and detecting transposable elements in genome sequences. Brief Bioinform 8:382–392

    CAS  PubMed  Google Scholar 

  • Britten RJ (2010) Transposable element insertions have strongly affected human evolution. Proc Natl Acad Sci USA 107:19945–19948

    CAS  PubMed  Google Scholar 

  • Chen K, Wallis JW, McLellan MD, Larson DE, Kalicki JM, Pohl CS, McGrath SD, Wendl MC, Zhang Q, Locke DP et al (2009) BreakDancer: an algorithm for high-resolution mapping of genomic structural variation. Nat Methods 6:677–681

    CAS  PubMed  PubMed Central  Google Scholar 

  • Conrad DF, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y, Aerts J, Andrews TD, Barnes C, Campbell P et al (2010) Origins and functional impact of copy number variation in the human genome. Nature 464:704–712

    CAS  PubMed  Google Scholar 

  • Cordaux R, Batzer MA (2009) The impact of retrotransposons on human genome evolution. Nat Rev Genet 10:691–703

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cost GJ, Feng Q, Jacquier A, Boeke JD (2002) Human L1 element target-primed reverse transcription in vitro. EMBO J 21:5899–5910

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cozar M, Bembi B, Dominissini S, Zampieri S, Vilageliu L, Grinberg D, Dardis A (2011) Molecular characterization of a new deletion of the GBA1 gene due to an inter Alu recombination event. Mol Genet Metab 102:226–228

    CAS  PubMed  Google Scholar 

  • Crooks GE, Hon G, Chandonia JM, Brenner SE (2004) WebLogo: a sequence logo generator. Genome Res 14:1188–1190

    CAS  PubMed  PubMed Central  Google Scholar 

  • Davis AJ, Chen DJ (2013) DNA double strand break repair via non-homologous end-joining. Transl Cancer Res 2:130–143

    CAS  PubMed  PubMed Central  Google Scholar 

  • Deininger PL, Moran JV, Batzer MA, Kazazian HH Jr (2003) Mobile elements and mammalian genome evolution. Curr Opin Genet Dev 13:651–658

    CAS  PubMed  Google Scholar 

  • Dewannieux M, Esnault C, Heidmann T (2003) LINE-mediated retrotransposition of marked Alu sequences. Nat Genet 35:41–48

    CAS  PubMed  Google Scholar 

  • Ewing AD (2015) Transposable element detection from whole genome sequence data. Mob DNA 6:24

    PubMed  PubMed Central  Google Scholar 

  • Fan X, Abbott TE, Larson D, Chen K (2014) BreakDancer: identification of genomic structural variation from paired-end read mapping. Curr Protoc Bioinform 45:15

    Google Scholar 

  • Feng Q, Moran JV, Kazazian HH Jr, Boeke JD (1996) Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. Cell 87:905–916

    CAS  PubMed  Google Scholar 

  • Freedman AH, Gronau I, Schweizer RM, Ortega-Del Vecchyo D, Han E, Silva PM, Galaverni M, Fan Z, Marx P, Lorente-Galdos B et al (2014) Genome sequencing highlights the dynamic early history of dogs. PLoS Genet 10:e1004016

    PubMed  PubMed Central  Google Scholar 

  • Goncalves A, Oliveira J, Coelho T, Taipa R, Melo-Pires M, Sousa M, Santos R (2017) Exonization of an intronic LINE-1 element causing Becker muscular dystrophy as a novel mutational mechanism in dystrophin gene. Genes (Basel) 8(10):253

    Google Scholar 

  • Goodier JL, Ostertag EM, Kazazian HH Jr (2000) Transduction of 3′-flanking sequences is common in L1 retrotransposition. Hum Mol Genet 9:653–657

    CAS  PubMed  Google Scholar 

  • Gu W, Zhang F, Lupski JR (2008) Mechanisms for human genomic rearrangements. Pathogenetics 1:4

    PubMed  PubMed Central  Google Scholar 

  • Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser (Oxf) 41:95–98

    CAS  Google Scholar 

  • Han K, Sen SK, Wang J, Callinan PA, Lee J, Cordaux R, Liang P, Batzer MA (2005) Genomic rearrangements by LINE-1 insertion-mediated deletion in the human and chimpanzee lineages. Nucleic Acids Res 33:4040–4052

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huang XQ, Zhou ZQ, Zhang XF, Chen CL, Tang Y, Zhu Q, Zhang JH, Xia JC (2017) Overexpression of SMOC2 attenuates the tumorigenicity of hepatocellular carcinoma cells and is associated with a positive postoperative prognosis in human hepatocellular carcinoma. J Cancer 8:3812–3827

    PubMed  PubMed Central  Google Scholar 

  • Hulsen T, de Vlieg J, Alkema W (2008) BioVenn–a web application for the comparison and visualization of biological lists using area-proportional Venn diagrams. BMC Genomics 9:488

    PubMed  PubMed Central  Google Scholar 

  • Irion DN, Schaffer AL, Famula TR, Eggleston ML, Hughes SS, Pedersen NC (2003) Analysis of genetic variation in 28 dog breed populations with 100 microsatellite markers. J Hered 94:81–87

    CAS  PubMed  Google Scholar 

  • Ishmukhametova A, Chen JM, Bernard R, de Massy B, Baudat F, Boyer A, Mechin D, Thorel D, Chabrol B, Vincent MC et al (2013) Dissecting the structure and mechanism of a complex duplication-triplication rearrangement in the DMD gene. Hum Mutat 34:1080–1084

    CAS  PubMed  Google Scholar 

  • Jones DT, Taylor WR, Thornton JM (1992) The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci 8:275–282

    CAS  PubMed  Google Scholar 

  • Kazazian HH Jr (2014) Processed pseudogene insertions in somatic cells. Mob DNA 5:20

    PubMed  PubMed Central  Google Scholar 

  • Kazazian HH Jr, Moran JV (1998) The impact of L1 retrotransposons on the human genome. Nat Genet 19:19–24

    CAS  PubMed  Google Scholar 

  • Kim S, Cho CS, Han K, Lee J (2016) Structural variation of Alu element and human disease. Genom Inform 14:70–77

    Google Scholar 

  • Kirkness EF, Bafna V, Halpern AL, Levy S, Remington K, Rusch DB, Delcher AL, Pop M, Wang W, Fraser CM et al (2003) The dog genome: survey sequencing and comparative analysis. Science 301:1898–1903

    PubMed  Google Scholar 

  • Kumar S, Stecher G, Tamura K (2016) MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874

    CAS  PubMed  Google Scholar 

  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    CAS  PubMed  Google Scholar 

  • Lee HE, Ayarpadikannan S, Kim HS (2015) Role of transposable elements in genomic rearrangement, evolution, gene regulation and epigenetics in primates. Genes Genet Syst 90:245–257

    CAS  PubMed  Google Scholar 

  • Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25:1754–1760

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, Clamp M, Chang JL, Kulbokas EJ 3rd, Zody MC et al (2005) Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438:803–819

    CAS  PubMed  Google Scholar 

  • Marchant TW, Johnson EJ, McTeir L, Johnson CI, Gow A, Liuti T, Kuehn D, Svenson K, Bermingham ML, Drogemuller M et al (2017) Canine brachycephaly is associated with a retrotransposon-mediated missplicing of SMOC2. Curr Biol 27(1573–1584):e1576

    Google Scholar 

  • Martin SL (2006) The ORF1 protein encoded by LINE-1: structure and function during L1 retrotransposition. J Biomed Biotechnol 2006:45621

    PubMed  PubMed Central  Google Scholar 

  • Mills RE, Walter K, Stewart C, Handsaker RE, Chen K, Alkan C, Abyzov A, Yoon SC, Ye K, Cheetham RK et al (2011) Mapping copy number variation by population-scale genome sequencing. Nature 470:59–65

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nozu K, Iijima K, Ohtsuka Y, Fu XJ, Kaito H, Nakanishi K, Vorechovsky I (2014) Alport syndrome caused by a COL4A5 deletion and exonization of an adjacent AluY. Mol Genet Genomic Med 2:451–453

    CAS  PubMed  PubMed Central  Google Scholar 

  • O’Donnell KA, Burns KH (2010) Mobilizing diversity: transposable element insertions in genetic variation and disease. Mob DNA 1:21

    PubMed  PubMed Central  Google Scholar 

  • Ostrander EA, Wayne RK (2005) The canine genome. Genome Res 15:1706–1716

    CAS  PubMed  Google Scholar 

  • Parker HG, Kim LV, Sutter NB, Carlson S, Lorentzen TD, Malek TB, Johnson GS, DeFrance HB, Ostrander EA, Kruglyak L (2004) Genetic structure of the purebred domestic dog. Science 304:1160–1164

    CAS  PubMed  Google Scholar 

  • Peeters T, Monteagudo S, Tylzanowski P, Luyten FP, Lories R, Cailotto F (2018) SMOC2 inhibits calcification of osteoprogenitor and endothelial cells. PLoS ONE 13:e0198104

    PubMed  PubMed Central  Google Scholar 

  • Pickeral OK, Makalowski W, Boguski MS, Boeke JD (2000) Frequent human genomic DNA transduction driven by LINE-1 retrotransposition. Genome Res 10:411–415

    CAS  PubMed  PubMed Central  Google Scholar 

  • Quinlan AR, Hall IM (2010) BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26:841–842

    CAS  PubMed  PubMed Central  Google Scholar 

  • Richardson SR, Doucet AJ, Kopera HC, Moldovan JB, Garcia-Perez JL, Moran JV (2015) The influence of LINE-1 and SINE retrotransposons on mammalian genomes. Microbiol Spectr 3:3

    Google Scholar 

  • Robberecht C, Voet T, Zamani Esteki M, Nowakowska BA, Vermeesch JR (2013) Nonallelic homologous recombination between retrotransposable elements is a driver of de novo unbalanced translocations. Genome Res 23:411–418

    CAS  PubMed  PubMed Central  Google Scholar 

  • Segal Y, Peissel B, Renieri A, de Marchi M, Ballabio A, Pei Y, Zhou J (1999) LINE-1 elements at the sites of molecular rearrangements in Alport syndrome-diffuse leiomyomatosis. Am J Hum Genet 64:62–69

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shearin AL, Ostrander EA (2010) Leading the way: canine models of genomics and disease. Dis Model Mech 3:27–34

    CAS  PubMed  PubMed Central  Google Scholar 

  • Swergold GD (1990) Identification, characterization, and cell specificity of a human LINE-1 promoter. Mol Cell Biol 10:6718–6729

    CAS  PubMed  PubMed Central  Google Scholar 

  • Szak ST, Pickeral OK, Landsman D, Boeke JD (2003) Identifying related L1 retrotransposons by analyzing 3′ transduced sequences. Genome Biol 4:R30

    PubMed  PubMed Central  Google Scholar 

  • Temtamy SA, Aglan MS, Valencia M, Cocchi G, Pacheco M, Ashour AM, Amr KS, Helmy SM, El-Gammal MA, Wright M et al (2008) Long interspersed nuclear element-1 (LINE1)-mediated deletion of EVC, EVC2, C4orf6, and STK32B in Ellis-van Creveld syndrome with borderline intelligence. Hum Mutat 29:931–938

    CAS  PubMed  Google Scholar 

  • VanBelzen DJ, Malik AS, Henthorn PS, Kornegay JN, Stedman HH (2017) Mechanism of deletion removing all dystrophin exons in a canine model for DMD implicates concerted evolution of X chromosome pseudogenes. Mol Ther Methods Clin Dev 4:62–71

    CAS  PubMed  Google Scholar 

  • Wang W, Kirkness EF (2005) Short interspersed elements (SINEs) are a major source of canine genomic diversity. Genome Res 15:1798–1808

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wayne RK (1993) Molecular evolution of the dog family. Trends Genet 9:218–224

    CAS  PubMed  Google Scholar 

  • Xing J, Wang H, Belancio VP, Cordaux R, Deininger PL, Batzer MA (2006) Emergence of primate genes by retrotransposon-mediated sequence transduction. Proc Natl Acad Sci USA 103:17608–17613

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (NRF-2016M3A9B6026771) and (NRF-2016M3A9B6026776).

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Authors and Affiliations

  1. Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea

    Songmi Kim, Seyoung Mun & Kyudong Han

  2. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea

    Taemook Kim

  3. Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea

    Kang-Hoon Lee & Je-Yoel Cho

  4. Department of Microbiology, Dankook University, Cheonan, 31116, Republic of Korea

    Keunsoo Kang

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  1. Songmi Kim
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Correspondence to Je-Yoel Cho or Kyudong Han.

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This study was reviewed and approved by the Seoul National University Institutional Animal Care and Use Committee (IACUC# SNU-170602-1).

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Supplementary material 1 (XLSX 10 kb)

335_2019_9812_MOESM2_ESM.xlsx

Supplementary material 2 (XLSX 2607 kb). Raw data of five structural variations in three dog predicted from three dog breeds genome using BreakDancer

Supplementary material 3 (XLSX 205 kb). A list of deletion SV candidates in each dog breed

Supplementary material 4 (XLSX 217 kb). Five different types of deletion SV events

Supplementary material 5 (XLSX 9458 kb). A list of full-length L1s identified in the three dog genome

335_2019_9812_MOESM6_ESM.pdf

Supplementary material 6 (PDF 58 kb). Molecular phylogenetic analysis of 10 mammals based on amino acids of 36 orthologs

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Kim, S., Mun, S., Kim, T. et al. Transposable element-mediated structural variation analysis in dog breeds using whole-genome sequencing. Mamm Genome 30, 289–300 (2019). https://doi.org/10.1007/s00335-019-09812-5

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