Probabilité et temps de fixation à l’aide de processus ancestraux

Ce mémoire analyse l’espérance du temps de fixation conditionnellement à ce qu’elle se produise et la probabilité de fixation d’un nouvel allèle mutant dans des populations soumises à différents phénomènes biologiques en uti- lisant l’approche des processus ancestraux. Tout d’abord, l’article de Tajima (1990) est analysé et les différentes preuves y étant manquantes ou incomplètes sont détaillées, dans le but de se familiariser avec les calculs du temps de fixa- tion. L’étude de cet article permet aussi de démontrer l’importance du temps de fixation sur certains phénomènes biologiques. Par la suite, l’effet de la sé- lection naturelle est introduit au modèle. L’article de Mano (2009) cite un ré- sultat intéressant quant à l’espérance du temps de fixation conditionnellement à ce que celle-ci survienne qui utilise une approximation par un processus de diffusion. Une nouvelle méthode utilisant le processus ancestral est présentée afin d’arriver à une bonne approximation de ce résultat. Des simulations sont faites afin de vérifier l’exactitude de la nouvelle approche. Finalement, un mo- dèle soumis à la conversion génique est analysé, puisque ce phénomène, en présence de biais, a un effet similaire à celui de la sélection. Nous obtenons finalement un résultat analytique pour la probabilité de fixation d’un nouveau mutant dans la population. Enfin, des simulations sont faites afin de détermi- nerlaprobabilitédefixationainsiqueletempsdefixationconditionnellorsque les taux sont trop grands pour pouvoir les calculer analytiquement.The expected time for fixation given its occurrence, and the probability of fixa- tion of a new mutant allele in populations subject to various biological phe- nomena are analyzed using the approach of the ancestral process. First, the paper of Tajima (1990) is analyzed, and the missing or incomplete proofs are fully worked out in this Master thesis in order to familiarize ourselves with calculations of fixation times. Our study of Tajima’s paper helps to show the importance of the fixation time in some biological phenomena. Thereafter, we extend the work of Tajima (1990) by introducing the effect of natural selec- tion in the model. Using a diffusion approximation, the work of Mano (2009) provides an interesting result about the expected time of fixation given its oc- currence. We derived an alternative method that uses an ancestral process that approximates well Mani’s result. Simulations are made to verify the accuracy ofthenewapproach.Finally,onemodelsubjecttogeneconversionisanalyzed, since this phenomenon, in the presence of bias, has a similar effect as selection. We deduce an analytical result for the probability of fixation of a new mutant in the population. Finally, simulations are made to determine the probability of fixation and the time of fixation given its occurrence when rates are too large to be calculated analytically

Prenatal Stress due to a Natural Disaster Predicts Adiposity in Childhood: The Iowa Flood Study

Prenatal stress can affect lifelong physical growth, including increased obesity risk. However, human studies remain limited. Natural disasters provide models of independent stressors unrelated to confounding maternal characteristics. We assessed degree of objective hardship and subjective distress in women pregnant during severe flooding. At ages 2.5 and 4 years we assessed body mass index (BMI), subscapular plus triceps skinfolds (SS + TR, an index of total adiposity), and SS: TR ratio (an index of central adiposity) in their children (n=106). Hierarchical regressions controlled first for several potential confounds. Controlling for these, flood exposure during early gestation predicted greater BMI increase from age 2.5 to 4, as well as total adiposity at 2.5. Greater maternal hardship and distress due to the floods, as well as other nonflood life events during pregnancy, independently predicted greater increase in total adiposity between 2.5 and 4 years. These results support the hypothesis that prenatal stress increases adiposity beginning in childhood and suggest that early gestation is a sensitive period. Results further highlight the additive effects of maternal objective and subjective stress, life events, and depression, emphasizing the importance of continued studies on multiple, detailed measures of maternal mental health and experience in pregnancy and child growth

Prenatal maternal stress was not associated with birthweight or gestational age at birth during COVID-19 restrictions in Australia : the BITTOC longitudinal cohort study

Background: Various forms of prenatal maternal stress (PNMS) have been reported to increase risk for preterm birth and low birthweight. However, the associations between specific components of stress – namely objective hardship and subjective distress - and birth outcomes are not well understood. Aims: Here, we aimed to determine the relationship between birthweight and gestational age at birth and specific prenatal factors (infant gender and COVID-19 pandemic-related objective hardship, subjective distress, change in diet), and to determine whether effects of hardship are moderated by maternal subjective distress, change in diet, or infant gender. Materials and methods: As part of the Birth in the Time of COVID (BITTOC study), women (N = 2285) who delivered in Australia during the pandemic were recruited online between August 2020 and February 2021. We assessed objective hardship and subjective distress related to the COVID pandemic and restrictions, and birth outcomes through questionnaires that were completed at recruitment and two months post-partum. Analyses included hierarchical multiple regressions. Results: No associations between maternal objective hardship or subjective distress and gestational age at birth or birthweight were identified. Lower birthweight was significantly associated with female gender (adjusted β = 0.083, P < 0.001) and with self-reported improvement in maternal diet (adjusted β = 0.059, P = 0.015). Conclusions: In a socioeconomically advantaged sample, neither objective hardship nor subjective distress related to COVID-19 were associated with birth outcomes. Further research is warranted to understand how other individual factors influence susceptibility to PNMS and how these findings are applicable to women with lower socioeconomic status

Le stress prénatal maternel d'une catastrophe naturelle réduit le niveau d'ARNm de GR-β placentaire

Le placenta humain régule le transfert du stress maternel au foetus, notamment via l’activité de l’enzyme 11β-hydroxystéroïde déshydrogénase de type 2 (11β-HSD2). La 11β-HSD2 convertit le cortisol maternel en cortisone, protégeant le foetus d’un excès de cortisol. Le stress maternel prénatal (PNMS) est associé à une diminution de l’activité de la 11β-HSD2 placentaire et avec une augmentation du cortisol foetal ce qui peut affecter le développement du foetus. La 11β- HSD2 placentaire joue un rôle direct dans la modulation des effets de l’exposition prénatale aux glucocorticoïdes endogènes, mais aussi un action indirect via l’activation des récepteurs aux glucorticoïdes (GR) ainsi que le transporteur placentaire de glucose de type 1 (GLUT-1). En outre, le PNMS a été associé à une diminution de l’expression de GLUT-1 et du transfert de glucose au foetus. L’objectif est de déterminer si les effets d’une exposition au PNMS (ex: une inondation) sont associés à une altération de l’expression et/ou de l’activité de la 11β-HSD2, de l’expression de GR, GLUT-1 au niveau du placenta. Le niveau d’ARNm a été évalué par RTqPCR sur les placentas issus d’une cohorte de femmes enceinte lors d’une inondation. Les résultats démontrent que le stress subjectif causé par une inondation réduit l’expression du GR-β, mais pas la 11β-HSD2. Cette étude est la première à mettre en lien le PNMS et le niveau de GR- β, ce qui implique une augmentation de réponse au cortisol en ne modifiant pas l’expression de la 11β-HSD2.</p

The effects of prenatal stress on early temperament: the 2011 Queensland flood study

This study examined the effects of disaster-related prenatal maternal stress on infant temperament and whether the sex of the infant or the timing of the stressor in pregnancy would moderate the effects.Mothers' objective experiences of a sudden-onset flood in Queensland, Australia, their subjective emotional reactions, and cognitive appraisal of the event were assessed. At 6 months postpartum, 121 mothers reported their infant's temperament on the 5 dimensions of the Short Temperament Scale for Infants.When controlling for postnatal maternal factors, subjective prenatal maternal stress and cognitive appraisal of the disaster were associated with easier aspects of infant temperament. However, several interesting interactions emerged showing negative effects of the flood. With higher levels of objective hardship in pregnancy, boys (but not girls) received more irritable temperament ratings. When the flood occurred early in pregnancy, higher levels of objective hardship predicted more arrhythmic infant temperament. Finally, mothers whose emotional response to the flood exceeded the hardship they endured reported significantly more active-reactive infants.Prenatal maternal stress from a natural disaster predicted more difficult temperament ratings that were moderated by infant sex, timing of the flood in gestation, and mother's emotional response to the disaster

Epigenetic modifications associated with maternal anxiety during pregnancy and children's behavioral measures

Epigenetic changes are associated with altered behavior and neuropsychiatric disorders and they modify the trajectory of aging. Maternal anxiety during pregnancy is a common environmental challenge for the fetus, causing changes in DNA methylation. Here, we determined the mediating role of DNA methylation and the moderating role of offspring sex on the association between maternal anxiety and children’s behavioral measures. In 83 mother–child dyads, maternal anxiety was assessed in each trimester of pregnancy when the child was four years of age. Children’s behavioral measures and children’s buccal DNA methylation levels (NR3C1, IGF2/H19 ICR, and LINE1) were examined. Higher maternal anxiety during the third trimester was associated with more methylation levels of the NR3C1. Moderating effects of sex on the association between maternal anxiety and methylation were found for IGF2/H19 and LINE1 CpGs. Mediation analysis showed that methylation of NR3C1 could buffer the effects of maternal anxiety on children’s behavioral measures, but this effect did not remain significant after controlling for covariates. In conclusion, our data support an association between maternal anxiety during pregnancy and DNA methylation. The results also underscore the importance of sex differences and timing effects. However, DNA methylation as underlying mechanism of the effect of maternal anxiety during pregnancy on offspring’s behavioral measures was not supported

Larger Amygdala Volume Mediates the Association Between Prenatal Maternal Stress and Higher Levels of Externalizing Behaviors: Sex Specific Effects in Project Ice Storm

Introduction: The amygdala is a brain structure involved in emotional regulation. Studies have shown that larger amygdala volumes are associated with behavioral disorders. Prenatal maternal depression is associated with structural changes in the amygdala, which in turn, is predictive of an increase in behavioral problems. Girls may be particularly vulnerable. However, it is not known whether disaster-related prenatal maternal stress (PNMS), or which aspect of the maternal stress experience (i.e., objective hardship, subjective distress, and cognitive appraisal), influences amygdala volumes. Nor is it known whether amygdala volumes mediate the effect of PNMS on behavioral problems in girls and boys.Aims: To assess whether aspects of PNMS are associated with amygdala volume, to determine whether timing of exposure moderates the effect, and to test whether amygdala volume mediates the association between PNMS and internalizing and externalizing problems in 11½ year old children exposed in utero, to varying levels of disaster-related PNMS.Methods: Bilateral amygdala volumes (AGV) and total brain volume (TBV) were acquired using magnetic resonance imaging, from 35 boys and 33 girls whose mothers were pregnant during the January 1998 Quebec Ice Storm. The mothers' disaster-related stress was assessed in June 1998. Child internalizing and externalizing problems were assessed at 11½ years using the Child Behavior Checklist (CBCL). Hierarchical regression analyses and mediation analyses were conducted on boys and girls separately, controlling for perinatal and postnatal factors.Results: In boys, subjective distress was associated with larger right AGV/TBV when mothers where exposed during late pregnancy, which in turn explained higher levels of externalizing behavior. However, when adjusting for postnatal factors, the effect was no longer significant. In girls, later gestational exposure to the ice storm was associated with larger AGV/TBV, but here, higher levels of objective PNMS were associated with more externalizing problems, which was, in part, mediated by larger AGV/TBV. No effects were detected on internalizing behaviors.Conclusion: These results suggest that the effects of PNMS on amygdala development and externalizing symptoms, as assessed in boys and girls in early adolescence, can be influenced by the timing of the stress in pregnancy, and the particular aspect of the mother's stress experience

Longitudinal associations between paternal mental health and child behavior and cognition in middle childhood

IntroductionPaternal mental health has been associated with adverse consequences on offspring psychosocial development, and family environmental factors may partly explain those associations. To clarify this, we need comprehensive prospective studies, particularly in middle-childhood when the child enters school and is expected to make use of behavioral and cognitive skills as part of their interactions and learning.MethodUsing data from a sub-sample of the prospective 3D birth cohort study comprised of mother-father-child triads, and a follow-up of the parents and the children at 6–8 years of age (n = 61; 36 boys, 25 girls), we examined whether paternal anxious and depressive symptoms measured during the pregnancy period (i.e., prenatally) or concurrently when the child was assessed at 6–8 years old were associated with children's cognition/behavior.ResultsIn contrast to our hypotheses, we found that greater prenatal paternal depressive symptoms predicted fewer child behavioral difficulties; and that greater concurrent childhood paternal depression or anxiety symptoms were associated with higher child full-scale IQ, controlling for the equivalent maternal mental health assessment and parental education. Father parenting perception did not mediate these associations, nor were they moderated by maternal mental health at the concurrent assessment, or paternal ratings of marital relationship quality.DiscussionThese findings suggest that higher symptoms of paternal mental health symptoms are associated with fewer child behavioral difficulties and higher cognitive performance in middle childhood. Potential clinical implications and future research directions are discussed

A trajectory analysis of childhood motor development following stress in pregnancy: the QF2011 flood study

This prospective, longitudinal cohort study examined the effects of flood-related stress in pregnancy on the trajectory of children's motor development; and the moderating effects of gestational timing of the flood or sex of the child. Women who were pregnant during a severe flood reported on their objective flood-related experiences, emotional reactions, and cognitive appraisal of the disaster. At 2-, 6-, 16-months, 2½- and 4-years postpartum, mothers' assessed their children's fine and gross motor development using the Ages and Stages-3 Questionnaire. High objective flood-exposure, or a negative appraisal, especially in later pregnancy, predicted poorer gross motor skills which rapidly improved across early childhood. Children's fine motor skill was influenced by the sex of the child with improvements in girls' fine motor skills over time, but not boys'. This demonstrates that stress in pregnancy has enduring influences on gross, but not fine, motor skills. Results are discussed in relation to fetal programming and stress appraisal theory

Positive cognitive appraisal “buffers” the long-term effect of peritraumatic distress on maternal anxiety: the Queensland Flood Study

Background: Limited research has evaluated distinct aspects of disaster experience as predictors of affective symptoms. In this study, we examined the extent to which maternal depression and anxiety over time were predicted by (1) objective hardship from a flood during pregnancy, (2) peritraumatic distress and (3) cognitive appraisal of the flood's consequences. Methods: Data were drawn from the 2011 Queensland Flood Study, a prospective, longitudinal study of pregnancy (n = 183). Mothers’ disaster experience was measured within 1 year after the flood. Their levels of depression, anxiety and stress were measured at 16 months, 30 months, 4 years and 6 years after childbirth. Linear mixed models were employed to evaluate symptom trajectories. Results: There were no time-dependent effects of disaster-related variables. Objective hardship did not predict outcomes. Peritraumatic distress significantly predicted depression and anxiety symptoms when cognitive appraisal was negative. Conversely, when cognitive appraisal was neutral or positive, the effect of peritraumatic distress was “buffered”. For anxiety, but not depression, this interaction survived Bonferroni correction. Neutral/ positive cognitive appraisal similarly moderated the effect of peritraumatic dissociation. Limitations: The generalizability of our findings is limited by overall low levels of depression and anxiety, along with a predominantly Caucasian, higher socioeconomic status sample. Potential confounders such as pre-disaster anxiety were not controlled for. Conclusion: In line with previous evidence, this study supports the predictive validity of peritraumatic distress for post-disaster depression and anxiety. Our findings suggest that cognitive appraisal could be a relevant target for interventions aimed at fostering maternal resilience