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Coping-Style Behavior Identified by a Survey of Parent-of-Origin Effects in the Rat.

ABSTRACT: In this study we investigate the effects of parent of origin on complex traits in the laboratory rat, with a focus on coping style behavior in stressful situations. We develop theory, based on earlier work, to partition heritability into a component due to a combination of parent of origin, maternal, paternal and shared environment, and another component that estimates classical additive genetic variance. We use this theory to investigate the effects on heritability of the parental origin of alleles in 798 outbred heterogeneous stock rats across 199 complex traits. Parent-of-origin-like heritability was on average 2.7fold larger than classical additive heritability. Among the phenotypes with the most enhanced parent-of-origin heritability were 10 coping style behaviors, with average 3.2 fold heritability enrichment. To confirm these findings on coping behavior, and to eliminate the possibility that the parent of origin effects are due to confounding with shared environment, we performed a reciprocal F1 cross between the behaviorally divergent RHA and RLA rat strains. We observed parent-of-origin effects on F1 rat anxiety/coping-related behavior in the Elevated Zero Maze test. Our study is the first to assess genetic parent-of-origin effects in rats, and confirm earlier findings in mice that such effects influence coping and impulsive behavior, and suggest these effects might be significant in other mammals, including humans.

SUBMITTER: Mont C

PROVIDER: S-EPMC6169385 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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Coping-Style Behavior Identified by a Survey of Parent-of-Origin Effects in the Rat.

Mont Carme C Hernandez-Pliego Polinka P Cañete Toni T Oliveras Ignasi I Río-Álamos Cristóbal C Blázquez Gloria G López-Aumatell Regina R Martínez-Membrives Esther E Tobeña Adolf A Flint Jonathan J Fernández-Teruel Alberto A Mott Richard R

G3 (Bethesda, Md.) 20181003 10

In this study we investigate the effects of parent of origin on complex traits in the laboratory rat, with a focus on coping style behavior in stressful situations. We develop theory, based on earlier work, to partition heritability into a component due to a combination of parent of origin, maternal, paternal and shared environment, and another component that estimates classical additive genetic variance. We use this theory to investigate the effects on heritability of the parental origin of all ...[more]

PMID: 30135107

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Project description:PurposeSex determining region Y (SRY)-box 2 (SOX2) anophthalmia syndrome is an autosomal dominant disorder manifesting as severe developmental eye malformations associated with brain, esophageal, genital, and kidney abnormalities. The syndrome is usually caused by de novo mutations or deletions in the transcription factor SOX2. To investigate any potential parental susceptibility factors, we set out to determine the parent of origin of the mutations or deletions, and following this, to determine if birth order or parental age were significant factors, as well as whether mutation susceptibility was related to any sequence variants in cis with the mutant allele.MethodsWe analyzed 23 cases of de novo disease to determine the parental origin of SOX2 mutations and deletions using informative single nucleotide polymorphisms and a molecular haplotyping approach. We examined parental ages for SOX2 mutation and deletion cases, compared these with the general population, and adjusted for birth order.ResultsAlthough the majority of subjects had mutations or deletions that arose in the paternal germline (5/7 mutation and 5/8 deletion cases), there was no significant paternal bias for new mutations (binomial test, p=0.16) or deletions (binomial test, p=0.22). For both mutation and deletion cases, there was no significant association between any single nucleotide polymorphism allele and the mutant chromosome (p>0.05). Parents of the subjects with mutations were on average older at the birth of the affected child than the general population by 3.8 years (p=0.05) for mothers and 3.3 years (p=0.66) for fathers. Parents of the subjects with deletions were on average younger than the general population by 3.0 years (p=0.17) for mothers and 2.1 years (p=0.19) for fathers. Combining these data, the difference in pattern of parental age between the subjects with deletions and mutations was evident, with a difference of 6.5 years for mothers (p=0.05) and 5.0 years for fathers (p=0.22), with the mothers and fathers of subjects with mutations being older than the mothers and fathers of subjects with deletions. We observed that 14 of the 23 (61%) affected children were the first-born child to their mother, with 10/15 of the mutation cases (66%) and 4/8 deletion cases (50%) being first born. This is in comparison to 35% of births with isolated congenital anomalies overall who are first born (p=0.008).ConclusionsSporadic SOX2 mutations and deletions arose in both the male and female germlines. In keeping with several genetic disorders, we found that SOX2 mutations were associated with older parental age and the difference was statistically significant for mothers (p=0.05), whereas, although not statistically significant, SOX2 deletion cases had younger parents. With the current sample size, there was no evidence that sequence variants in cis surrounding SOX2 confer susceptibility to either mutations or deletions.

Project description:BackgroundNonsuicidal self-injury (NSSI) behaviors-an important factor that profoundly affects the physical and mental health of young people-are induced by complex and diverse factors, while showing significant differences at the gender level. We examined mediating behaviors among parenting styles, students' coping styles, and endogenous and exogenous influencing variables of adolescents' NSSI behaviors.MethodsIn this cross-sectional study, Secondary school students in Ningbo, Zhejiang Province, China (n = 2,689; F/M:1532/1157) were surveyed for basic attributes, parenting styles, coping styles, and NSSI behaviors. After the initial screening of the sample data, several external derivatives were screened based on the single factor analysis method. On this basis, the construction of path analysis models under multivariate multiple elicitations was carried out.ResultsThe overall prevalence of NSSI was 15.16%, and the incidence of NSSI in boys was lower than that in girls (OR = 0.334, 95% CI [0.235-0.474]). The path analysis model data fit well; the indicators of female and male part are: CFI = 0.913/0.923, GFI = 0.964/0.977, SRMR = 0.055/0.047, RMSEA = 0.097/0.069 with 90% confidence interval (CI) [0.084-0.111]/[0.054-0.084]. For female, when negative coping style and extreme education affect NSSI respectively, the standardized path coefficient values are 0.478 (z = 20.636, P = 0.000 < 0.01) and 0.151 (z = 6.524, P = 0.000 < 0.01) respectively, while for male, the corresponding values become 0.225 (z = 7.057, P < 0.001) and 0.104 (z = 3.262, P < 0.001).ConclusionIn particular, we investigated the mediating effects of gender-specific NSSI influences and found that NSSI behaviors were strongly associated with environmental variables and individual factors, especially family parenting style and adolescent coping style, which influenced NSSI in a gender-specific manner. The results showed that males were the target of both positive and negative parenting styles, whereas females were more likely to choose negative coping styles directed towards emotions in response to external stimuli, and instead showed a more significant predisposition towards NSSI behaviors. This phenomenon seems to be influenced by multilevel factors such as sociocultural, individual value identity, and physiological structure differences. In the path analysis model with the introduction of mediating effects, the influence of gender differences on NSSI behavior becomes more pronounced under the interaction of multiple factors: women seem to be more significantly influenced by the external derivatives in the internal derivatives than male subjects, and are more likely to trigger NSSI behavior under the interaction of multiple factors. These findings effectively reveal the significant role of different end-influencing factors in NSSI behaviors at the level of gender differences, which can provide effective theoretical support to prevent and treat NSSI behaviors in adolescents.

Dataset Information

Coping-Style Behavior Identified by a Survey of Parent-of-Origin Effects in the Rat.

Publications

Coping-Style Behavior Identified by a Survey of Parent-of-Origin Effects in the Rat.

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