7:00 am - 8:00 am
Event details: A graduate exam seminar is a presentation of the student’s final research project for their degree. This is an ALES PhD Final Exam Seminar by Haesu Ko. This seminar is open to the general public to attend.
Zoom Link: https://ualberta-ca.zoom.us/j/95263742992?pwd=9v9N5lud1BeU1uwQaZ0Pjzd417XY06.1
PhD with Drs. Graham Plastow and John Harding
Thesis Topic: Identification of genetic variants impacting fetal outcomes following in utero porcine reproductive and respiratory syndrome virus challenge
Abstract:
Porcine reproductive and respiratory syndrome (PRRS) remains one of the most economically damaging viral diseases in swine, causing an estimated annual loss exceeding $1.2 billion in the U.S. alone. While substantial host genetics research has focused on PRRS control in nursery and growing pigs, far less is known about the genetic factors influencing fetal responses during late-gestation PRRSV infection. A previous genome-wide association study (GWAS) (trial-1) identified a significant single nucleotide polymorphism (SNP), DRGA0008048, on pig chromosome 7 linked to fetal viability. This SNP is located near thyroid-related genes DIO2 and TSHR, which are positional candidates potentially affecting fetal resilience through thyroid hormone metabolism, known to be disrupted during severe PRRSV infection. This thesis explores the role of genetic variants in the DIO2–TSHR region and other fetal genomic regions in modulating fetal resilience to maternal PRRSV-2 infection.
An independent maternal PRRSV-2 challenge trial (trial-2) investigated the DRGA SNP near DIO2. The favorable B allele, previously associated with higher fetal viability, was significantly related to lower fetal serum T4 levels, but it did not predict improved fetal viability. A follow-up study identified a missense variant (p.Asn91Ser) in DIO2 via targeted Sanger sequencing. While this mutation was associated with increased DIO2 mRNA expression in fetal heart and kidney tissues, its effect on fetal viability was minimal. To explore discrepancies between the original GWAS finding and these results, pooled whole-genome sequencing of the DIO2–TSHR region was conducted in trial-2 gilts, alongside Sanger sequencing of selected DIO2 SNPs in parental animals across both trials. This revealed shifts in genotype and haplotype frequencies in BB genotyped gilts, suggesting that selection or genetic drift over time may have disrupted linkage between the DRGA SNP and causal variants responsible for fetal viability.
Finally, integrating fetal genotypes with thymic RNA sequencing data in fetuses categorized by PRRS susceptibility demonstrated that severe fetal infection was related to downregulation of early thymocyte development genes and upregulation of interferon-driven pathways. Interaction expression QTL analyses identified genotype by PRRS susceptibility group effects in immune-related genes, such as TMEM98, implicated in T helper 1 (Th1) cell differentiation, highlighting a complex interplay between host genetics and fetal thymic transcriptional responses in reproductive PRRS. These transcriptional responses and associated DNA variants could be applied to predict fetal PRRS susceptibility.
Collectively, current evidence indicates that the DIO2 locus is not yet definitively proven for improving fetal resilience in reproductive PRRS. By combining genomic and transcriptomic analyses, this thesis expanded our understanding of fetal pig responses to PRRSV-2 infection at late gestation, ultimately guiding future efforts to identify causal variants and robust biomarkers for enhanced reproductive outcomes in PRRS-challenged sow herds.
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