Biology subjects

Hunter, M. D.

Publications and source records attributed to Hunter, M. D..

3 recordsLinked to original sources

bioRxiv2024

Detecting mtDNA effects with an Extended Pedigree Model: An Analysis of Statistical Power and Estimation Bias

Mitochondrial DNA (mtDNA) plays a crucial role in numerous cellular processes, yet its impact on human behavior remains underexplored. The current paper proposes a novel covariance structure model with seven parameters to specifically isolate and quantify mtDNA effects on human behavior. This approach uses extended pedigrees to obtain estimates of mtDNA variance while controlling for other genetic and environmental influences. Our Monte-Carlo simulations indicate that a sample size of approximately 5,000 individuals is sufficient to detect medium mtDNA effects (mt2 = 5%), while a more substantial cohort of around 30,000 is required for small effects (mt2 = 1%). We show that deeper pedigrees increase power to detect the mtDNA effect while wider pedigrees decrease power, given the equal total sample size. We evaluated how missing kinship records and mtDNA mutations impact bias. Both lead to underestimation of mtDNA variance, and an overestimation of the interaction between nuclear DNA and mtDNA. In addition, the false positive rate of mtDNA effect estimation is low when fitting the model with data generated without mtDNA effects. Collectively, we demonstrate that using extended pedigrees to quantify the influence of mtDNA on human behavior is robust and powerful.

genetics↗

bioRxiv2020

Multilevel Twin Models: Geographical Region as a Third Level Variable

The classical twin model can be reparametrized as an equivalent multilevel model. The multilevel parameterization has underexplored advantages, such as the possibility to include higher-level clustering variables in which lower levels are nested. When this higher-level clustering is not modeled, its variance is captured by the common environmental variance component. In this paper we illustrate the application of a 3-level multilevel model to twin data by analyzing the regional clustering of 7-year-old childrens height in the Netherlands. Our findings show that 1.8%, of the phenotypic variance in childrens height is attributable to regional clustering, which is 7% of the variance explained by between-family or common environmental components. Since regional clustering may represent ancestry, we also investigate the effect of region after correcting for genetic principal components, in a subsample of participants with genome-wide SNP data. After correction, region did no longer explain variation in height. Our results suggest that the phenotypic variance explained by region actually represent ancestry effects on height.

genetics↗

bioRxiv2019

Transcriptomics of monarch butterflies (Danaus plexippus) reveals strong differential gene expression in response to host plant toxicity, but weak response to parasite infection

Herbivorous insects have evolved many mechanisms to overcome plant chemical defenses, including detoxification and sequestration. Herbivores may also use toxic plants to reduce parasite infection. Plant toxins could directly interfere with parasites or could enhance endogenous immunity. Alternatively, plant toxins could favor down-regulation of endogenous immunity by providing an alternative (exogenous) defense against parasitism. However, studies on genome-wide transcriptomic responses to plant defenses and the interplay between host plant toxicity and parasite infection remain rare. Monarch butterflies (Danaus plexippus) are specialist herbivores that feed on milkweeds (Asclepias spp.), which contain toxic cardenolides. Monarchs have adapted to cardenolides through multiple resistance mechanisms and can sequester cardenolides to defend against bird predators. In addition, high-cardenolide milkweeds confer medicinal effects to monarchs against a specialist protozoan parasite (Ophryocystis elektroscirrha). We used this system to study the interplay between the effects of plant toxicity and parasite infection on global gene expression. Our results demonstrate that monarch larvae differentially express several hundred genes when feeding on A. curassavica and A. incarnata, two species that are similar in nutritional content but differ substantially in cardenolide concentrations. These differentially expressed genes include genes within multiple families of canonical insect detoxification genes, suggesting that they play a role in monarch toxin resistance and sequestration. Interestingly, we found little transcriptional response to infection. However, parasite growth was reduced in monarchs reared on A. curassavica, and in these monarchs, a small number of immune genes were down-regulated, consistent with the hypothesis that medicinal plants can reduce reliance on endogenous immunity.

genomics↗