Location: Genetics and Animal Breeding
Title: The enigmatic role of host genetics in disease susceptibility: a case study of Porcine circovirus 2Author
WALKER, LIANNA - University Of Nebraska | |
ENGLE, TAYLOR - University Of Nebraska | |
VU, HIEP - University Of Nebraska | |
TOSKY, EMILY - University Of Nebraska | |
Nonneman, Danny - Dan | |
Smith, Timothy - Tim | |
BORZA, TUDOR - Dalhousie University | |
BURKEY, THOMAS - University Of Nebraska | |
PLASTOW, GRAHAM - University Of Alberta | |
KACHMAN, STEPHEN - University Of Nebraska | |
CIOBANU, DANIEL - University Of Nebraska |
Submitted to: Plant and Animal Genome Conference Proceedings
Publication Type: Abstract Only Publication Acceptance Date: 12/21/2018 Publication Date: 1/16/2019 Citation: Walker, L.R., Engle, T.B., Vu, H., Tosky, E.R., Nonneman, D.J., Smith, T.P.L., Borza, T., Burkey, T.E., Plastow, G.S., Kachman, S.D., Ciobanu, D.C. 2019. The enigmatic role of host genetics in disease susceptibility: a case study of Porcine circovirus 2 [abstract]. In: Plant and Animal Genome Conference Proceedings XXVII, 12-16 January 2019, San Diego, CA. pg. 232. W1128. Available: https://www.intlpag.org/2019/images/pdf/2019/PAGXXVII-abstracts-workshops.pdf Interpretive Summary: Technical Abstract: Porcine circovirus 2 (PCV2), the smallest known mammalian virus, is a circular single-stranded DNA virus responsible for a group of diseases collectively known as PCV2 Associated Diseases (PCVAD). Variation in the incidence and severity of PCVAD exists between pigs suggesting a host genetic component involved in pathogenesis. A genome-wide association study based on experimental infection (n=974), provided evidence of a host genetic role in PCV2 viremia, immune response and growth during challenge. Host genotype explained 64% of the phenotypic variation for overall viral load, with two major QTLs identified on chromosome 7 (SSC7) near the SLA class II locus and on the proximal end of chromosome 12 (SSC12). Dissection of the SSC12 QTL based on gene annotation, genomic and RNA-sequencing, suggested that a missense mutation in the SYNGR2 (SYNGR2 p.Arg63Cys) gene is potentially responsible for the variation in viremia. PCV2 titer in PK15 cells decreased when the expression of SYNGR2 was silenced by specific-siRNA or in a PK15 edited clone carrying a partial deletion of the second exon that harbors a key domain and the SYNGR2 p.Arg63Cys. Identification of a non-conservative substitution in this key domain of SYNGR2 suggests that the SYNGR2 p.Arg63Cys substitution may underlie the observed genetic effect on viral load. The knowledge generated by this research will result in a reduction in susceptibility to PCV2 and improvement in the general health and welfare of pigs. |