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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.

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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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