Genetic architecture of gene expression underlying variation in host response to porcine reproductive and respiratory syndrome virus infection

Kommadath, Arun; Bao, Hua; Choi, Igseo; Reecy, James M.; Koltes, James E.; Fritz-Waters, Eric R.; Eisley, Christopher J.; Grant, Jason R.; Rowland, R.; Tuggle, Christopher K.; Dekkers, Jack C. M.; Lunney, Joan K.; Guan, Le Luo; Stothard, Paul; Plastow, Graham

doi:10.1038/srep46203

Cited by 26 publications

(19 citation statements)

References 54 publications

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“…We were able to recapitulate the GS stress conditions found in primary MEFs from livers of calorie-restricted mice. Consistent with previous studies, we detected gene expression profile differences associated with caloric restriction (e.g., ADRA2A, CTGF and LAIR1) (Ogawa et al, 2011;Swindell, 2009;Yamamoto et al, 2009), but also new potential markers involved in obesity (NRIP3) (Wen et al, 2019) and immune response (HS3ST4, GBP6) (Kommadath et al, 2017;Stacey et al, 2017).…”

Section: Discussionsupporting

confidence: 90%

SirT7 auto-ADP-ribosylation regulates glucose starvation response through macroH2A1.1

Simonet

Vázquez

Ianni

et al. 2019

Preprint

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Sirtuins are key players in the response to oxidative, metabolic and genotoxic stress, and are involved in genome stability, metabolic homeostasis and aging.Originally described as NAD + -dependent deacetylases, some sirtuins are also characterized by a poorly understood mono-ADP-ribosyltransferase (mADPRT) activity. Here we report that the deacetylase SirT7 is a dual sirtuin as it also features auto-mADPRT activity. Molecular and structural evidence suggests that this novel activity occurs at a second previously undefined active site that is physically separated in another domain. Specific abrogation of this activity alters SirT7 chromatin distribution, suggesting a role for this modification in SirT7 chromatin binding specificity. We uncover an epigenetic pathway by which ADPribosyl-SirT7 is recognized by the ADP-ribose reader macroH2A1.1, a histone variant involved in chromatin organization, metabolism and differentiation. Glucose starvation (GS) boosts this interaction and promotesSirT7 relocalization to intergenic regions in a macroH2A1-dependent manner. Both SirT7 activities are in turn required to promote GS-dependent enrichment of macroH2A1 in a subset of nearby genes, which results in their specific up-or downregulation. Consistently, the expression changes of these genes associated to calorie restriction (CR) or aging are abrogated in SirT7 -/mice, reinforcing the link between Sirtuins, CR and aging. Our work provides a novel perspective about sirtuin duality and suggests a key role for SirT7/macroH2A1.1 axis in mammalian glucose homeostasis, calorie restriction signaling and aging.

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Section: Discussionsupporting

confidence: 90%

SirT7 auto-ADP-ribosylation regulates glucose starvation response through macroH2A1.1

Simonet

Vázquez

Ianni

et al. 2019

Preprint

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“…The unfavorable G allele codes for the truncated GBP5 protein which is not able to inhibit viral entry and replication as quickly as the intact GBP5 protein [ 28 ] thus leading to a poor outcome of homozygous individuals following PRRS virus infection. Moreover, the quoted SNP has been shown to be a cis eQTL [ 30 ]. With the exception of three breeds showing intermediate frequencies (Cinta Senese, Lithuanian indigenous wattle and Mora Romagnola), the unfavorable allele shows very high frequency in all breeds (>0.73), opening potential selection possibilities.…”

Section: Resultsmentioning

confidence: 99%

Diversity across major and candidate genes in European local pig breeds

Muñoz¹,

Bozzi

García³

et al. 2018

PLoS ONE

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The aim of this work was to analyse the distribution of causal and candidate mutations associated to relevant productive traits in twenty local European pig breeds. Also, the potential of the SNP panel employed for elucidating the genetic structure and relationships among breeds was evaluated. Most relevant genes and mutations associated with pig morphological, productive, meat quality, reproductive and disease resistance traits were prioritized and analyzed in a maximum of 47 blood samples from each of the breeds (Alentejana, Apulo-Calabrese, Basque, Bísara, Majorcan Black, Black Slavonian (Crna slavonska), Casertana, Cinta Senese, Gascon, Iberian, Krškopolje (Krškopoljski), Lithuanian indigenous wattle, Lithuanian White Old Type, Mora Romagnola, Moravka, Nero Siciliano, Sarda, Schwäbisch-Hällisches Schwein (Swabian Hall pig), Swallow-Bellied Mangalitsa and Turopolje). We successfully analyzed allelic variation in 39 polymorphisms, located in 33 candidate genes. Results provide relevant information regarding genetic diversity and segregation of SNPs associated to production and quality traits. Coat color and morphological trait-genes that show low level of segregation, and fixed SNPs may be useful for traceability. On the other hand, we detected SNPs which may be useful for association studies as well as breeding programs. For instance, we observed predominance of alleles that might be unfavorable for disease resistance and boar taint in most breeds and segregation of many alleles involved in meat quality, fatness and growth traits. Overall, these findings provide a detailed catalogue of segregating candidate SNPs in 20 European local pig breeds that may be useful for traceability purposes, for association studies and for breeding schemes. Population genetic analyses based on these candidate genes are able to uncover some clues regarding the hidden genetic substructure of these populations, as the extreme genetic closeness between Iberian and Alentejana breeds and an uneven admixture of the breeds studied. The results are in agreement with available knowledge regarding breed history and management, although largest panels of neutral markers should be employed to get a deeper understanding of the population’s structure and relationships.

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“…ATG9B is one of the main genes involved in autophagy and has been found to be associated with initiating autophagy 44 . CMPK2 is believed to be associated with macrophage terminal differentiation and was recently found to be a candidate gene for association with lower weight gain and increased viraemia levels in response to porcine reproductive and respiratory syndrome virus infection while showing evidence of allele specific expression in pigs 45 . These findings suggest mutations associated with immunity have become fixed in the Brahman breed, and could be one reason why the Brahman breed is so resilient and resistant to a range of pathogens that affect Bos taurus breeds.…”

Section: Resultsmentioning

confidence: 99%

Sequencing the mosaic genome of Brahman cattle identifies historic and recent introgression including polled

Koufariotis

Hayes

Kelly³

et al. 2018

Sci Rep

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Brahman cattle have a Bos indicus and Bos taurus mosaic genome, as a result of the process used to create the breed (repeat backcrossing of Bos taurus females to Bos indicus bulls). With the aim of identifying Bos taurus segments in the Brahman genome at sequence level resolution, we sequenced the genomes of 46 influential Brahman bulls. Using 36 million variants identified in the sequences, we searched for regions close to fixation for Bos indicus or Bos taurus segments that were longer than expected by chance (from simulation of the breed formation history of Brahman cattle). Regions close to fixation for Bos indicus content were enriched for protein synthesis genes, while regions of higher Bos taurus content included genes of the G-protein coupled receptor family (including genes implicated in puberty, such as THRS). The region with the most extreme Bos taurus enrichment was on chromosome 14 surrounding PLAG1. The introgressed Bos taurus allele at PLAG1 increases stature and the high frequency of the allele likely reflects strong selection for the trait. Finally, we provide evidence that the polled mutation in Brahmans, a desirable trait under very strong recent selection, is of Celtic origin and is introgressed from Bos taurus.

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Genetic architecture of gene expression underlying variation in host response to porcine reproductive and respiratory syndrome virus infection

Cited by 26 publications

References 54 publications

SirT7 auto-ADP-ribosylation regulates glucose starvation response through macroH2A1.1

SirT7 auto-ADP-ribosylation regulates glucose starvation response through macroH2A1.1

Diversity across major and candidate genes in European local pig breeds

Sequencing the mosaic genome of Brahman cattle identifies historic and recent introgression including polled

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