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Mayo, L. M., Asratian, A., Lindé, J., Holm, L., Nätt, D., Augier, G., . . . Heilig, M. (2018). Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice. Molecular Psychiatry
Open this publication in new window or tab >>Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice
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2018 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578Article in journal (Refereed) Epub ahead of print
Abstract [en]

Post-traumatic stress disorder (PTSD) is a common, debilitating condition with limited treatment options. Extinction of fear memories through prolonged exposure therapy, the primary evidence-based behavioral treatment for PTSD, has only partial efficacy. In mice, pharmacological inhibition of fatty acid amide hydrolase (FAAH) produces elevated levels of anandamide (AEA) and promotes fear extinction, suggesting that FAAH inhibitors may aid fear extinction-based treatments. A human FAAH 385C-greater thanA substitution encodes an FAAH enzyme with reduced catabolic efficacy. Individuals homozygous for the FAAH 385A allele may therefore offer a genetic model to evaluate the impact of elevations in AEA signaling in humans, helping to inform whether FAAH inhibitors have the potential to facilitate fear extinction therapy for PTSD. To overcome the challenge posed by low frequency of the AA genotype (appr. 5%), we prospectively genotyped 423 individuals to examine the balanced groups of CC, AC, and AA individuals (n = 25/group). Consistent with its loss-of-function nature, the A allele was dose dependently associated with elevated basal AEA levels, facilitated fear extinction, and enhanced the extinction recall. Moreover, the A-allele homozygotes were protected against stress-induced decreases in AEA and negative emotional consequences of stress. In a humanized mouse model, AA homozygous mice were similarly protected against stress-induced decreases in AEA, both in the periphery, and also in the amygdala and prefrontal cortex, brain structures critically involved in fear extinction and regulation of stress responses. Collectively, these data suggest that AEA signaling can temper aspects of the stress response and that FAAH inhibition may aid the treatment for stress-related psychiatric disorders, such as PTSD.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-154914 (URN)10.1038/s41380-018-0215-1 (DOI)30120421 (PubMedID)2-s2.0-85052287102 (Scopus ID)
Available from: 2019-03-05 Created: 2019-03-05 Last updated: 2019-05-01Bibliographically approved
Elfwing, M., Nätt, D., Goerlich-Jansson, V. C., Persson, M., Hjelm, J. & Jensen, P. (2015). Early stress causes sex-specific, life-long changes in behaviour, levels of gonadal hormones, and gene expression in chickens. PLoS ONE, 10(5), Article ID e0125808.
Open this publication in new window or tab >>Early stress causes sex-specific, life-long changes in behaviour, levels of gonadal hormones, and gene expression in chickens
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0125808Article in journal (Refereed) Published
Abstract [en]

Early stress can have long-lasting phenotypic effects. Previous research shows that male and female chickens differ in many behavioural aspects, and respond differently to chronic stress. The present experiment aimed to broadly characterize long-term sex differences in responses to brief events of stress experienced during the first weeks of life. Chicks from a commercial egg-laying hybrid were exposed to stress by inducing periods of social isolation during their first three weeks of life, followed by a broad behavioural, physiological and genomic characterization throughout life. Early stressed males, but not females, where more anxious in an open field-test, stayed shorter in tonic immobility and tended to have delayed sexual maturity, as shown by a tendency for lower levels of testosterone compared to controls. While early stressed females did not differ from non-stressed in fear and sexual maturation, they were more socially dominant than controls. The differential gene expression profile in hypothalamus was significantly correlated from 28 to 213 days of age in males, but not in females. In conclusion, early stress had a more pronounced long-term effect on male than on female chickens, as evidenced by behavioral, endocrine and genomic responses. This may either be attributed to inherent sex differences due to evolutionary causes, or possibly to different stress related selection pressures on the two sexes during commercial chicken breeding.

Place, publisher, year, edition, pages
Public Library of Science, 2015
National Category
Biological Sciences
Identifiers
urn:nbn:se:liu:diva-117423 (URN)10.1371/journal.pone.0125808 (DOI)000354916100036 ()
Available from: 2015-04-27 Created: 2015-04-27 Last updated: 2019-03-05Bibliographically approved
Nätt, D., Johansson, I., Faresjö, T., Ludvigsson, J. & Thorsell, A. (2015). High cortisol in 5-year-old children causes loss of DNA methylation in SINE retrotransposons: a possible role for ZNF263 in stress-related diseases. Clinical Epigenetics, 7(1), Article ID 91.
Open this publication in new window or tab >>High cortisol in 5-year-old children causes loss of DNA methylation in SINE retrotransposons: a possible role for ZNF263 in stress-related diseases
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2015 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, ISSN 1868-7083, Vol. 7, no 1, article id 91Article in journal (Refereed) Published
Abstract [en]

Background: Childhood stress leads to increased risk of many adult diseases, such as major depression and cardiovascular disease. Studies show that adults with experienced childhood stress have specific epigenetic changes, but to understand the pathways that lead to disease, we also need to study the epigenetic link prospectively in children. Results: Here, we studied a homogenous group of 48 5-year-old children. By combining hair cortisol measurements (a well-documented biomarker for chronic stress), with whole-genome DNA-methylation sequencing, we show that high cortisol associates with a genome-wide decrease in DNA methylation and targets short interspersed nuclear elements (SINEs; a type of retrotransposon) and genes important for calcium transport: phenomena commonly affected in stress-related diseases and in biological aging. More importantly, we identify a zinc-finger transcription factor, ZNF263, whose binding sites where highly overrepresented in regions experiencing methylation loss. This type of zinc-finger protein has previously shown to be involved in the defense against retrotransposons. Conclusions: Our results show that stress in preschool children leads to changes in DNA methylation similar to those seen in biological aging. We suggest that this may affect future disease susceptibility by alterations in the epigenetic mechanisms that keep retrotransposons dormant. Future treatments for stress-and age-related diseases may therefore seek to target zinc-finger proteins that epigenetically control retrotransposon reactivation, such as ZNF263.

Place, publisher, year, edition, pages
BioMed Central, 2015
Keywords
Stress; DNA methylation; ZNF263; Children; Retrotransposon; Cortisol; Transcription factor; EGR1; Blood; Hair
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-122055 (URN)10.1186/s13148-015-0123-z (DOI)000360619500001 ()26339299 (PubMedID)
Note

Funding Agencies|Centre for Systems Neurobiology at Linkoping University; Swedish Research Council [K2005-72X-11242-11A, K2008-69X-20826-01-4]; Swedish Child Diabetes Foundation; JDRF Wallenberg Foundation [K 98-99D-12813-01A]; Medical Research Council of Southeast Sweden (FORSS); Swedish Council for Working Life and Social Research [FAS2004-1775]

Available from: 2015-12-18 Created: 2015-10-19 Last updated: 2019-03-05
Nätt, D., Agnvall, B. & Jensen, P. (2014). Large Sex Differences in Chicken Behavior and Brain Gene Expression Coincide with Few Differences in Promoter DNA-Methylation. PLoS ONE, 9(4), e96376
Open this publication in new window or tab >>Large Sex Differences in Chicken Behavior and Brain Gene Expression Coincide with Few Differences in Promoter DNA-Methylation
2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 4, p. e96376-Article in journal (Refereed) Published
Abstract [en]

While behavioral sex differences have repeatedly been reported across taxa, the underlying epigenetic mechanisms in thebrain are mostly lacking. Birds have previously shown to have only limited dosage compensation, leading to high sex bias ofZ-chromosome gene expression. In chickens, a male hyper-methylated region (MHM) on the Z-chromosome has beenassociated with a local type of dosage compensation, but a more detailed characterization of the avian methylome islimiting our interpretations. Here we report an analysis of genome wide sex differences in promoter DNA-methylation andgene expression in the brain of three weeks old chickens, and associated sex differences in behavior of Red Junglefowl(ancestor of domestic chickens). Combining DNA-methylation tiling arrays with gene expression microarrays we show that aspecific locus of the MHM region, together with the promoter for the zinc finger RNA binding protein (ZFR) gene onchromosome 1, is strongly associated with sex dimorphism in gene expression. Except for this, we found few differences inpromoter DNA-methylation, even though hundreds of genes were robustly differentially expressed across distantly relatedbreeds. Several of the differentially expressed genes are known to affect behavior, and as suggested from their functionalannotation, we found that female Red Junglefowl are more explorative and fearful in a range of tests performed throughouttheir lives. This paper identifies new sites and, with increased resolution, confirms known sites where DNA-methylationseems to affect sexually dimorphic gene expression, but the general lack of this association is noticeable and strengthensthe view that birds do not have dosage compensation.

Place, publisher, year, edition, pages
Public Library of Science, 2014
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-106374 (URN)10.1371/journal.pone.0096376 (DOI)000335504900030 ()
Available from: 2014-05-06 Created: 2014-05-06 Last updated: 2019-03-05Bibliographically approved
Nätt, D., Rubin, C.-J., Wright, D., Johnsson, M., Beltéky, J., Andersson, L. & Jensen, P. (2012). Heritable genome-wide variation of gene expression and promoter methylation between wild and domesticated chickens. BMC Genomics, 13(59)
Open this publication in new window or tab >>Heritable genome-wide variation of gene expression and promoter methylation between wild and domesticated chickens
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2012 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 13, no 59Article in journal (Refereed) Published
Abstract [en]

Variations in gene expression, mediated by epigenetic mechanisms, may cause broad phenotypic effects in animals. However, it has been debated to what extent expression variation and epigenetic modifications, such as patterns of DNA methylation, are transferred across generations, and therefore it is uncertain what role epigenetic variation may play in adaptation. Here, we show that in Red Junglefowl, ancestor of domestic chickens, gene expression and methylation profiles in thalamus/hypothalamus differ substantially from that of a domesticated egg laying breed. Expression as well as methylation differences are largely maintained in the offspring, demonstrating reliable inheritance of epigenetic variation. Some of the inherited methylation differences are tissue-specific, and the differential methylation at specific loci are little changed after eight generations of intercrossing between Red Junglefowl and domesticated laying hens. There was an over-representation of differentially expressed and methylated genes in selective sweep regions associated with chicken domestication. Hence, our results show that epigenetic variation is inherited in chickens, and we suggest that selection of favourable epigenomes, either by selection of genotypes affecting epigenetic states, or by selection of methylation states which are inherited independently of sequence differences, may have been an important aspect of chicken domestication.

Place, publisher, year, edition, pages
BioMed Central, 2012
Keywords
Domestication, gene expression, tiling array, behaviour, methylation
National Category
Biological Sciences
Identifiers
urn:nbn:se:liu:diva-70159 (URN)10.1186/1471-2164-13-59 (DOI)000301440800001 ()
Note

funding agencies|Swedish Research Council| 2008-14496-59340-36 |Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning| 221 2007 838 |

Available from: 2011-08-22 Created: 2011-08-22 Last updated: 2019-03-05Bibliographically approved
Goerlich, V. C., Nätt, D., Elfwing, M., Macdonald, B. & Jensen, P. (2012). Transgenerational effects of early experience on acute stress reactions in behaviour, steroid hormones and gene expression in the precocial chicken. Hormones and Behavior, 61(5), 711-718
Open this publication in new window or tab >>Transgenerational effects of early experience on acute stress reactions in behaviour, steroid hormones and gene expression in the precocial chicken
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2012 (English)In: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 61, no 5, p. 711-718Article in journal (Refereed) Published
Abstract [en]

Stress during early life can profoundly influence an individual’s phenotype. Effects can manifest in the short-term as well as later in life and even in subsequent generations. Transgenerational effects of stress are potentially mediated via modulation of the hypothalamic-pituitary-adrenal axis (HPA) as well as epigenetic mechanisms causing heritable changes in gene expression. To investigate these pathways we subjected domestic chicks (Gallus gallus) to intermittent social isolation, food restriction, and temperature stress for the first three weeks of life. The early life stress resulted in a dampened corticosterone response to restraint stress in the parents and male offspring. Stress-specific genes, such as early growth response 1 (EGR1) and corticotropin releasing hormone receptor 1 (CRHR1), were upregulated when chicks were tested in the context of restraint stress, but not under baseline conditions. Treatment differences in gene expression were also correlated across generations which indicate transgenerational epigenetic inheritance, possibly mediated by differences in maternal yolk estradiol and testosterone. In an associative learning test early stressed birds made more correct choices suggesting a higher coping ability in stressful situations. This study is the first to show transgenerational effects of early life stress in a precocial species by combining behavioural, endocrinological, and transcriptomic measurements.

Keywords
Early growth response, corticotropin releasing hormone receptor, postnatal stress, behaviour, epigenetics, transgenerational effects, steroid hormones, gene expression
National Category
Biological Sciences
Identifiers
urn:nbn:se:liu:diva-70157 (URN)10.1016/j.yhbeh.2012.03.006 (DOI)000304339800007 ()
Note
funding agencies|Swedish Research Council||Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning||Available from: 2011-08-22 Created: 2011-08-22 Last updated: 2019-03-05
Nätt, D. (2011). Heritable epigenetic responses to environmental challenges: Effects on behaviour, gene expression and DNA-methylation in the chicken. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Heritable epigenetic responses to environmental challenges: Effects on behaviour, gene expression and DNA-methylation in the chicken
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Phenotypic variation within populations is a crucial factor in evolution and is mainly thought to be driven by heritable changes in the base sequence of DNA. Among our domesticated species we find some of the most variable species on earth today. This variety of breeds has appeared during a relatively short evolutionary time, and so far genetic studies have been unable to explain but a small portion of this variation, which indicates more novel mechanisms of inheritance and phenotypic plasticity. The aim of this study was therefore to investigate some of these alternative routes in the chicken, especially focusing on transgenerational effects of environmental challenges on behaviour and gene expression in relation to domestication. In two experiments a chronically unpredictable environment induced phenotypic changes in the parents that were mirrored in the unexposed offspring raised without parental contact. This transmission was especially clear in domesticated birds. A third experiment showed that repeated stress events very early in life could change the developmental program making the birds more resistant to stress later in life. Here, the phenotypic changes were also mirrored in the unexposed offspring and associated with inheritance of gene expression. Epigenetic factors, such as DNA-methylation, could play an important role in the mechanism of these transgenerational effects. A fourth experiment showed that wild types and domesticated chickens differed substantially in their patterns of DNA-methylation, where the domesticated breed had increased amount of promoter DNA-methylation. In line with the previous experiments, this breed also showed increased transmission of methylation marks to their  offspring. Conclusively, parental exposure of environmental challenges that introduce changes in behaviour, physiology and gene expression can under both chronic and temporal conditions be heritably programmed in the parent and transmitted to the unexposed offspring. Since heritable epigenetic variation between wild type and domesticated chickens is stable and numerous, it is possible that selection for favourable epigenomes could add another level to the evolutionary processes and therefore might explain some of the rapid changes in the history of the domesticated chicken. 

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. p. 53
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1383
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-70155 (URN)978-91-7393-123-6 (ISBN)
Public defence
2011-09-16, Planck, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 09:15 (English)
Opponent
Supervisors
Available from: 2011-08-22 Created: 2011-08-22 Last updated: 2019-12-19Bibliographically approved
Jöngren, M., Westander, J., Nätt, D. & Jensen, P. (2010). Brain gene expression in relation to fearfulness in female red junglefowl (Gallus gallus). Genes, Brain and Behavior, 9(7), 751-758
Open this publication in new window or tab >>Brain gene expression in relation to fearfulness in female red junglefowl (Gallus gallus)
2010 (English)In: Genes, Brain and Behavior, ISSN 1601-1848, E-ISSN 1601-183X, Vol. 9, no 7, p. 751-758Article in journal (Refereed) Published
Abstract [en]

The biology of fear is central to animal welfare and hasbeen a major target for selection during domestication.Fear responses were studied in female red junglefowl(RJF), the ancestor of domesticated chickens. A totalof 31 females were tested in a ground predator test,an aerial predator test and a tonic immobility (TI)test, in order to assess their level of fearfulnessacross different situations. Two to six variables fromeach test were entered into a principal component(PC) analysis, which showed one major fearfulnesscomponent (explaining 27% of the variance). Based onthe PC scores, four high- and four low-fearful birds werethen selected for gene expression analysis. From eachof these birds, the midbrain region (including thalamus,hypothalamus, pituitary, mesencephalon, pons, nucleustractus solitarii and medulla oblongata), was collectedand global gene expression compared between groupsusing a 14k chicken cDNA microarray. There were 13significantly differentially expressed (DE) genes (basedonM > 1 andB > 0; FDR-adjusted P < 0.05) between thefearful and non-fearful females. Among the DE genes,we identified the neuroprotein Axin1, two potentialDNA/RNA regulating proteins and a retrotransposontranscript situated in a well-studied quantitative traitloci (QTL) region on chromosome 1, known to affectseveral domestication-related traits. The differentiallyexpressed genes may be part of a possible molecularmechanism controlling fear responses in fowl.

Place, publisher, year, edition, pages
International and Neural genetics Society, 2010
Keywords
Chicken, domestication, fear, gene expression, microarray
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-59967 (URN)10.1111/j.1601-183X.2010.00612.x (DOI)000282634300009 ()
Available from: 2010-10-01 Created: 2010-10-01 Last updated: 2019-03-05Bibliographically approved
Nätt, D., Lindqvist, N., Stranneheim, H., Lundeberg, J., Torjesen, P. A. & Jensen, P. (2009). Inheritance of Acquired Behaviour Adaptions and Brain Gene Expression in Chickens. PLoS ONE, 4(7), e6405
Open this publication in new window or tab >>Inheritance of Acquired Behaviour Adaptions and Brain Gene Expression in Chickens
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2009 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, no 7, p. e6405-Article, review/survey (Other academic) Published
Abstract [en]

Background: Environmental challenges may affect both the exposed individuals and their offspring. We investigated possible adaptive aspects of such cross-generation transmissions, and hypothesized that chronic unpredictable food access would cause chickens to show a more conservative feeding strategy and to be more dominant, and that these adaptations would be transmitted to the offspring.

Methodology/Principal Findings: Parents were raised in an unpredictable (UL) or in predictable diurnal light rhythm (PL, 12:12 h light:dark). In a foraging test, UL birds pecked more at freely available, rather than at hidden and more attractive food, compared to birds from the PL group. Female offspring of UL birds, raised in predictable light conditions without parental contact, showed a similar foraging behavior, differing from offspring of PL birds. Furthermore, adult offspring of UL birds performed more food pecks in a dominance test, showed a higher preference for high energy food, survived better, and were heavier than offspring of PL parents. Using cDNA microarrays, we found that the differential brain gene expression caused by the challenge was mirrored in the offspring. In particular, several immunoglobulin genes seemed to be affected similarly in both UL parents and their offspring. Estradiol levels were significantly higher in egg yolk from UL birds, suggesting one possible mechanism for these effects.

Conclusions/Significance: Our findings suggest that unpredictable food access caused seemingly adaptive responses in feeding behavior, which may have been transmitted to the offspring by means of epigenetic mechanisms, including regulation of immune genes. This may have prepared the offspring for coping with an unpredictable environment.

Citation: Nätt D, Lindqvist N, Stranneheim H, Lundeberg J, Torjesen PA, et al. (2009) Inheritance of Acquired Behaviour Adaptations and Brain Gene Expression in Chickens. PLoS ONE 4(7): e6405. doi:10.1371/journal.pone.0006405

Editor: Tom Pizzari, University of Oxford, United Kingdom

Received: March 26, 2009; Accepted: June 30, 2009; Published: July 28, 2009

Copyright: © 2009 Nätt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This project was funded by the Swedish Research Council (VR; www.vr.se; grant nrs 50280101 and 50280102) and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas; www.formas.se; grant no 221-2005-270). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the mauscript.

Competing interests: The authors have declared that no competing interests exist.

 

National Category
Biological Sciences
Identifiers
urn:nbn:se:liu:diva-19948 (URN)10.1371/journal.pone.0006405 (DOI)
Note
Original Publication: Daniel Nätt, Niclas Lindqvist, Henrik Stranneheim, Joakim Lundeberg, Peter A. Torjesen and Per Jensen, Inheritance of Acquired Behaviour Adaptions and Brain Gene Expression in Chickens, 2009, PLoS ONE, (4), 7, e6405. http://dx.doi.org/10.1371/journal.pone.0006405 Copyright: Authors Available from: 2009-08-25 Created: 2009-08-19 Last updated: 2019-03-05Bibliographically approved
Nätt, D. (2008). Stress and the Offspring: Adaptive Transgenerational Effects of Unpredictability on Behaviour and Gene Expression in Chickens (Gallus gallus). (Licentiate dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Stress and the Offspring: Adaptive Transgenerational Effects of Unpredictability on Behaviour and Gene Expression in Chickens (Gallus gallus)
2008 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Environmental stress has shown to affect both the exposed individuals and the development of their offspring. Generally, it is thought that the stressed organism responds to stress by trying to adapt to it. This thesis investigates possible evolutionary consequences of cross-generational transmissions of stress, where the parent has been stressed but the offspring has not. In two studies we have exposed chicken parents of different breeds to an unpredictable circadian light rhythm, to investigate the influence of genetic background on the transmission of behaviour and patterns of genome-wide gene expression across generations. In Paper I, we can show that the domesticated chicken, by means of epigenetic factors, transmit their behaviours as well as their gene expression profiles to their offspring to a higher extent than their wild ancestor, the red junglefowl. Furthermore, in Paper II, even though the offspring never experienced the stress or had any contact with their stressed parents, they seemed to have adapted to it, which suggests that the parents might have prepared (or pre-adapted) them for living in the unpredictable environment. Additionally, eggs of stressed hens showed increased levels of estradiol that might have affected gene expression of specific immune genes, which were up-regulated in the offspring of stressed parents. It is possible that the traditional distinction between stress responses and evolutionary adaptation may be reevaluated, since our results indicate that they could be parts of the same evolutionary event.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2008. p. 22
Series
Linköping Studies in Science and Technology. Thesis, ISSN 0280-7971 ; 1385
Keywords
Chicken, Red junglefowl, Domestication, Epigenetics, Transgenerational, Inheritance, Gene expression, Microarray, qRT-PCR, Immunogenetics, Immunoglobulin, Estradiol, Steriod hormones, Prenatal stress, Epigenetic inheritance, Adaptation, Stress, Behaviour
Identifiers
urn:nbn:se:liu:diva-15518 (URN)978-91-7393-753-5 (ISBN)
Presentation
2008-12-04, Schrödinger E324, Linköpings Universitet, Department of Physics, Chemistry and Biology, 58183 Linköping, Sweden , Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2008-11-14 Created: 2008-11-13 Last updated: 2019-03-05Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-9182-9401

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