Pig genome functional annotation enhances the biological interpretation of complex traits and human disease

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Zhangyuan Pan
  • Yuelin Yao
  • Hongwei Yin
  • Zexi Cai
  • Ying Wang
  • Lijing Bai
  • Colin Kern
  • Michelle Halstead
  • Ganrea Chanthavixay
  • Nares Trakooljul
  • Klaus Wimmers
  • Goutam Sahana
  • Guosheng Su
  • Mogens Sandø Lund
  • Catherine W. Ernst
  • Pablo Ross
  • Christopher K. Tuggle
  • Lingzhao Fang
  • Huaijun Zhou

The functional annotation of livestock genomes is crucial for understanding the molecular mechanisms that underpin complex traits of economic importance, adaptive evolution and comparative genomics. Here, we provide the most comprehensive catalogue to date of regulatory elements in the pig (Sus scrofa) by integrating 223 epigenomic and transcriptomic data sets, representing 14 biologically important tissues. We systematically describe the dynamic epigenetic landscape across tissues by functionally annotating 15 different chromatin states and defining their tissue-specific regulatory activities. We demonstrate that genomic variants associated with complex traits and adaptive evolution in pig are significantly enriched in active promoters and enhancers. Furthermore, we reveal distinct tissue-specific regulatory selection between Asian and European pig domestication processes. Compared with human and mouse epigenomes, we show that porcine regulatory elements are more conserved in DNA sequence, under both rapid and slow evolution, than those under neutral evolution across pig, mouse, and human. Finally, we provide biological insights on tissue-specific regulatory conservation, and by integrating 47 human genome-wide association studies, we demonstrate that, depending on the traits, mouse or pig might be more appropriate biomedical models for different complex traits and diseases.

OriginalsprogEngelsk
Artikelnummer5848
TidsskriftNature Communications
Vol/bind12
Udgave nummer1
ISSN2041-1723
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
This study was supported by Agriculture and Food Research Initiative Competitive Grants no. 2018-67015-27501 (C.K.T., H.Z., C.E., and P.R.) and no. 2015-67015-22940 (H.Z. and P.R.) from the USDA National Institute of Food and Agriculture, Multistate Research Project NRSP8 and NC1170 (H.Z.), and the California Agricultural Experimental Station (H.Z.).

Publisher Copyright:
© 2021, The Author(s).

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