| 1. |
- da Silva, Arthur Nery, et al.
(författare)
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How Epigenetics Can Enhance Pig Welfare?
- 2022
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Ingår i: Animals. - : MDPI. - 2076-2615. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary In the pig industry, new market trends and consumer demands have emerged over the past decades, which includes increased concerns about how animals are raised on farms. As a consequence of consumers concerns, technologies capable of predicting animal welfare on farms have been explored. One of the technologies that are permeating the frontier of knowledge in this area are epigenetic biomarkers. Epigenetic biomarkers are biochemical markers surrounding the genome, which may be able to predict the exposures that individuals had during their lifetime. These markers represent an advance in the molecular level accuracy to support the current welfare indicators. In this literature review focused on pigs, we show some studies already carried out, we performed an integrative analysis of the already reported genes surrounding epi-biomarkers, and we highlight the benefits of investing efforts in this research field to enhance animal welfare and consumers trust. Epigenetics works as an interface between the individual and its environment to provide phenotypic plasticity to increase individual adaptation capabilities. Recently, a wide variety of epi-genetic findings have indicated evidence for its application in the development of putative epi-biomarkers of stress in farm animals. The purpose of this study was to evaluate previously reported stress epi-biomarkers in swine and encourage researchers to investigate potential paths for the development of a robust molecular tool for animal welfare certification. In this literature review, we report on the scientific concerns in the swine production chain, the management carried out on the farms, and the potential implications of these practices for the animals welfare and their epigenome. To assess reported epi-biomarkers, we identified, from previous studies, potentially stress-related genes surrounding epi-biomarkers. With those genes, we carried out a functional enrichment analysis of differentially methylated regions (DMRs) of the DNA of swine subjected to different stress-related conditions (e.g., heat stress, intrauterine insult, and sanitary challenges). We identified potential epi-biomarkers for target analysis, which could be added to the current guidelines and certification schemes to guarantee and certify animal welfare on farms. We believe that this technology may have the power to increase consumers trust in animal welfare.
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| 2. |
- Guerrero Bosagna, Carlos, et al.
(författare)
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DNA methylation variation in the brain of laying hens in relation to differential behavioral patterns
- 2020
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Ingår i: Comparative Biochemistry and Physiology - Part D. - : ELSEVIER SCIENCE INC. - 1744-117X .- 1878-0407. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Domesticated animals are unique to investigate the contribution of genetic and non-genetic factors to specific phenotypes. Among non-genetic factors involved in phenotype formation are epigenetic mechanisms. Here we aimed to identify whether relative DNA methylation differences in the nidopallium between groups of individuals are among the non-genetic factors involved in the emergence of differential behavioral patterns in hens. The nidopallium was selected due to its important role in complex cognitive function (i.e., decision making) in birds. Behavioral patterns that spontaneously emerge in hens living in a highly controlled environment were identified with a unique tracking system that recorded their transitions between pen zones. Behavioral activity patterns were characterized through three classification schemes: (i) daily specific features of behavioral routines (Entropy), (ii) daily spatio-temporal activity patterns (Dynamic Time Warping), and (iii) social leading behavior (Leading Index). Unique differentially methylated regions (DMRs) were identified between behavioral patterns emerging within classification schemes, with entropy having the higher number. Functionally, DTW had double the proportion of affected promoters and half of the distal intergenic regions. Pathway enrichment analysis of DMR-associated genes revealed that Entropy relates mainly to cell cycle checkpoints, Leading Index to mitochondrial function, and DTW to gene expression regulation. Our study suggests that different biological functions within neurons (particularly in the nidopallium) could be responsible for the emergence of distinct behavior patterns and that epigenetic variation within brain tissues would be an important factor to explain behavioral variation.
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| 3. |
- Lees, John, 1986-, et al.
(författare)
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The mitoepigenome responds to stress, suggesting novel mito-nuclear interactions in vertebrates
- 2023
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Ingår i: BMC Genomics. - : BMC. - 1471-2164. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- The mitochondria are central in the cellular response to changing environmental conditions resulting from disease states, environmental exposures or normal physiological processes. Although the influences of environmental stressors upon the nuclear epigenome are well characterized, the existence and role of the mitochondrial epigenome remains contentious. Here, by quantifying the mitochondrial epigenomic response of pineal gland cells to circadian stress, we confirm the presence of extensive cytosine methylation within the mitochondrial genome. Furthermore, we identify distinct epigenetically plastic regions (mtDMRs) which vary in cytosinic methylation, primarily in a non CpG context, in response to stress and in a sex-specific manner. Motifs enriched in mtDMRs contain recognition sites for nuclear-derived DNA-binding factors (ATF4, HNF4A) important in the cellular metabolic stress response, which we found to be conserved across diverse vertebrate taxa. Together, these findings suggest a new layer of mito-nuclear interaction in which the nuclear metabolic stress response could alter mitochondrial transcriptional dynamics through the binding of nuclear-derived transcription factors in a methylation-dependent context.
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| 4. |
- Nunes, J. R. S., et al.
(författare)
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Genome-wide association study reveals genes associated with the absence of intermuscular bones in tambaqui (Colossoma macropomum)
- 2020
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Ingår i: Animal Genetics. - : WILEY. - 0268-9146 .- 1365-2052. ; 51:6, s. 899-909
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Tidskriftsartikel (refereegranskat)abstract
- The presence of intermuscular bones in fisheries products limits the consumption and commercialization potential of many fish species, including tambaqui (Colossoma macropomum). These bones have caused medical emergencies and are an undesirable characteristic for fish farming because their removal is labor-intensive during fish processing. Despite the difficulty in identifying genes related to the lack of intermuscular bone in diverse species of fish, the discovery of individuals lacking intermuscular bones in a Neotropical freshwater characiform fish has provided a unique opportunity to delve into the genetic mechanisms underlying the pathways of intermuscular bone formation. In this study, we carried out a GWAS among boneless and wt tambaqui populations to identify markers associated with a lack of intermuscular bone. After analyzing 11 416 SNPs in 360 individuals (12 boneless and 348 bony), we report 675 significant (P-adj < 0.003) associations for this trait. Of those, 13 associations were located near candidate genes related to the reduction of bone mass, promotion of bone formation, inhibition of bone resorption, central control of bone remodeling, bone mineralization and other related functions. To the best of our knowledge, for the first time, we have successfully identified genes related to a lack of intermuscular bones using GWAS in a non-model species.
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| 5. |
- Pertille, Fabio, et al.
(författare)
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DNA methylation profiles in red blood cells of adult hens correlate with their rearing conditions
- 2017
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Ingår i: Journal of Experimental Biology. - : COMPANY OF BIOLOGISTS LTD. - 0022-0949 .- 1477-9145. ; 220:19, s. 3579-3587
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Tidskriftsartikel (refereegranskat)abstract
- Stressful conditions are common in the environment where production animals are reared. Stress in animals is usually determined by the levels of stress-related hormones. A big challenge, however, is in determining the history of exposure of an organism to stress, because the release of stress hormones can show an acute (and recent) but not a sustained exposure to stress. Epigenetic tools provide an alternative option to evaluate past exposure to long-termstress. Chickens provide a unique model to study stress effects in the epigenome of red blood cells (RBCs), a cell type of easy access and nucleated in birds. The present study investigated whether two different rearing conditions in chickens can be identified by looking at DNA methylation patterns in their RBCs later in life. These conditions were rearing in open aviaries versus in cages, which are likely to differ regarding the amount of stress they generate. Our comparison revealed 115 genomic windows with significant changes in RBC DNA methylation between experimental groups, which were located around 53 genes and within 22 intronic regions. Our results set the ground for future detection of long-term stress in live production animals by measuring DNA methylation in a cell type of easy accessibility.
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| 6. |
- Pértille, Fábio, et al.
(författare)
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High-throughput and Cost-effective Chicken Genotyping Using Next-Generation Sequencing
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Chicken genotyping is becoming common practice in conventional animal breeding improvement.Despite the power of high-throughput methods for genotyping, their high cost limits large scale use inanimal breeding and selection. In the present paper we optimized the CornellGBS, an efficient and costeffectivegenotyping by sequence approach developed in plants, for its application in chickens. Herewe describe the successful genotyping of a large number of chickens (462) using CornellGBS approach.Genomic DNA was cleaved with the PstI enzyme, ligated to adapters with barcodes identifyingindividual animals, and then sequenced on Illumina platform. After filtering parameters were applied,134,528 SNPs were identified in our experimental population of chickens. Of these SNPs, 67,096 hada minimum taxon call rate of 90% and were considered ‘unique tags’. Interestingly, 20.7% of theseunique tags have not been previously reported in the dbSNP. Moreover, 92.6% of these SNPs wereconcordant with a previous Whole Chicken-genome re-sequencing dataset used for validation purposes.The application of CornellGBS in chickens showed high performance to infer SNPs, particularly inexonic regions and microchromosomes. This approach represents a cost-effective (~US$50/sample)and powerful alternative to current genotyping methods, which has the potential to improve wholegenomeselection (WGS), and genome-wide association studies (GWAS) in chicken production.
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| 7. |
- Pértille, Fábio, et al.
(författare)
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Mutation dynamics of CpG dinucleotides during a recent event of vertebrate diversification.
- 2019
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Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 14:7, s. 685-707
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation in CpGs dinucleotides is associated with high mutability and disappearance of CpG sites during evolution. Although the high mutability of CpGs is thought to be relevant for vertebrate evolution, very little is known on the role of CpG-related mutations in the genomic diversification of vertebrates. Our study analysed genetic differences in chickens, between Red Junglefowl (RJF; the living closest relative to the ancestor of domesticated chickens) and domesticated breeds, to identify genomic dynamics that have occurred during the process of their domestication, focusing particularly on CpG-related mutations. Single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) between RJF and these domesticated breeds were assessed in a reduced fraction of their genome. Additionally, DNA methylation in the same fraction of the genome was measured in the sperm of RJF individuals to identify possible correlations with the mutations found between RJF and the domesticated breeds. Our study shows that although the vast majority of CpG-related mutations found relate to CNVs, CpGs disproportionally associate to SNPs in comparison to CNVs, where they are indeed substantially under-represented. Moreover, CpGs seem to be hotspots of mutations related to speciation. We suggest that, on the one hand, CpG-related mutations in CNV regions would promote genomic 'flexibility' in evolution, i.e., the ability of the genome to expand its functional possibilities; on the other hand, CpG-related mutations in SNPs would relate to genomic 'specificity' in evolution, thus, representing mutations that would associate with phenotypic traits relevant for speciation.
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| 8. |
- Pértille, Fábio, et al.
(författare)
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Putative Epigenetic Biomarkers of Stress in Red Blood Cells of Chickens Reared Across Different Biomes
- 2020
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Production animals are constantly subjected to early adverse environmental conditionsthat influence the adult phenotype and produce epigenetic effects. CpG dinucleotidemethylation in red blood cells (RBC) could be a useful epigenetic biomarker to identifyanimals subjected to chronic stress in the production environment. Here we compareda reduced fraction of the RBC methylome of chickens exposed to social isolation tonon-exposed. These experiments were performed in two different locations: Brazil andSweden. The aim was to identify stress-associated DNA methylation profiles in RBC across these populations, in spite of the variable conditions to which birds are exposedin each facility and their different lineages. Birds were increasingly exposed to a socialisolation treatment, combined with food and water deprivation, at random periods of theday from weeks 1–4 after hatching. We then collected the RBC DNA from individualsand compared a reduced fraction of their methylome between the experimental groupsusing two bioinformatic approaches to identify differentially methylated regions (DMRs):one using fixed-size windows and another that preselected differential peaks with MACS2. Three levels of significance were used (P ≤ 0.05, P ≤ 0.005, and P ≤ 0.0005) to identify DMRs between experimental groups, which were then used for differentanalyses. With both of the approaches more DMRs reached the defined significancethresholds in BR individuals compared to SW. However, more DMRs had higher foldchange values in SW compared to BR individuals. Interestingly, ChrZ was enrichedabove expectancy for the presence of DMRs. Additionally, when analyzing the locationsof these DMRs in relation to the transcription starting site (TSS), we found threepeaks with high DMR presence: 10 kb upstream, the TSS itself, and 20–40 kbdownstream. Interestingly, these peaks had DMRs with a high presence (>50%) ofspecific transcription factor binding sites. Three overlapping DMRs were found betweenthe BR and SW population using the most relaxed p-value (P ≤ 0.05). With the most stringent p-value (P ≤ 0.0005), we found 7 and 4 DMRs between treatmentsin the BR and SW populations, respectively. This study is the first approximation toidentify epigenetic biomarkers of long-term exposure to stress in different lineages ofproduction animals.
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| 9. |
- Pértille, Fábio, et al.
(författare)
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Sperm Methylome Profiling Can Discern Fertility Levels in the Porcine Biomedical Model
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:5
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Tidskriftsartikel (refereegranskat)abstract
- A combined Genotyping By Sequencing (GBS) and methylated DNA immunoprecipitation (MeDIP) protocol was used to identify-in parallel-genetic variation (Genomic-Wide Association Studies (GWAS) and epigenetic differences of Differentially Methylated Regions (DMR) in the genome of spermatozoa from the porcine animal model. Breeding boars with good semen quality (n = 11) and specific and well-documented differences in fertility (farrowing rate, FR) and prolificacy (litter size, LS) (n = 7) in artificial insemination programs, using combined FR and LS, were categorized as High Fertile (HF, n = 4) or Low Fertile (LF, n = 3), and boars with Unknown Fertility (UF, n = 4) were tested for eventual epigenetical similarity with those fertility-proven. We identified 165,944 Single Nucleotide Polymorphisms (SNPs) that explained 14-15% of variance among selection lines. Between HF and LF individuals (n = 7, 4 HF and 3 LF), we identified 169 SNPs with p <= 0.00015, which explained 58% of the variance. For the epigenetic analyses, we considered fertility and period of ejaculate collection (late-summer and mid-autumn). Approximately three times more DMRs were observed in HF than in LF boars across these periods. Interestingly, UF boars were clearly clustered with one of the other HF or LF groups. The highest differences in DMRs between HF and LF experimental groups across the pig genome were located in the chr 3, 9, 13, and 16, with most DMRs being hypermethylated in LF boars. In both HF and LF boars, DMRs were mostly hypermethylated in late-summer compared to mid-autumn. Three overlaps were detected between SNPs (p <= 0.0005, n = 1318) and CpG sites within DMRs. In conclusion, fertility levels in breeding males including FR and LS can be discerned using methylome analyses. The findings in this biomedical animal model ought to be applied besides sire selection for andrological diagnosis of idiopathic sub/infertility.
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| 10. |
- Rezaei, Shiva, et al.
(författare)
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GBS-MeDIP : A protocol for parallel identification of genetic and epigenetic variation in the same reduced fraction of genomes across individuals
- 2022
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Ingår i: STAR protocols. - : Cell Press. - 2666-1667. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The GBS-MeDIP protocol combines two previously described techniques, Geno-type-by-Sequencing (GBS) and Methylated-DNA- Immunoprecipitation (MeDIP). Our method allows for parallel and cost-efficient interrogation of genetic and methylomic variants in the DNA of many reduced genomes, taking advantage of the barcoding of DNA samples performed in the GBS and the subsequent creation of DNA pools, then used as an input for the MeDIP. The GBS-MeDIP is particularly suitable to identify genetic and methylomic biomarkers when resources for whole genome interrogation are lacking.
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