Genetic variability | EPFL Graph Search

Genetic variability is either the presence of, or the generation of, genetic differences. It is defined as "the formation of individuals differing in genotype, or the presence of genotypically different individuals, in contrast to environmentally induced differences which, as a rule, cause only temporary, nonheritable changes of the phenotype". Genetic variability in a population is important for biodiversity. Causes There are many sources of genetic variability in a population: *Homologous recombination is a significant source of variability. During meiosis in sexual organisms, two homologous chromosomes cross over one another and exchange genetic material. The chromosomes then split apart and are ready to contribute to forming an offspring. Recombination is random and is governed by its own set of genes. Being controlled by genes means that recombination is variable in frequency. *Immigration, emigration, and translocation – each of these is the movement of an indi

The role and transcriptional regulation of FAM46A in adipocyte differentiation

Ann-Kristin Hov

Obesity is currently a leading global health concern. Treatments include undergoing a weight-loss regimen. However, successful weight-loss is variable, where the heritability of obesity is considered part of the cause. This patient variability to weight-loss was addressed by Carayol et al. (2017), where protein plasma level changes was associated to genetic variability and changes in BMI under a low-calorie diet intervention. A highly significant association region was found to regulate downstream gene FAM46A; coding for a nucleotidyl-transferase protein. Loss of function mutations in FAM46A have previously been discovered in multiple human diseases, such as osteogenesis imperfecta. However, there is a lack of understanding of FAM46Aâs function, especially in the context of adipose tissue and metabolism. This thesis aimed to follow up on the Carayol et al. study by investigating the transcriptional regulation of FAM46A and how the associated region is influencing this regulation, as well as how FAM46A is involved in adipose tissue function. When mapping the physical DNA interaction network around the associated region using chromosome conformation capture (3C) in human subcutaneous adipocytes (SGBS cells), no interactions between the FAM46A promoter and selected loci of the associated region were found. Interestingly, significant interaction peaks downstream of the promoter overlapped with regions of open chromatin and were enriched for transcription factor (TF) motifs that are involved in stem cell differentiation and TGFÎ² signalling. SMAD4, part of the TGFÎ² signalling pathway, binds to this region, indicating a potential regulator of FAM46A. To address FAM46Aâs potential role in adipocyte function, FAM46A expression was disrupted in vitro in differentiating adipocytes. Reduction of FAM46A expression in SGBS cells resulted in decreased expression of PPARG and CEBPA, the master regulators of adipogenesis, complemented by a reduction in lipid accumulation. Follow up studies in murine mesenchymal stem cells where Fam46a was over-expressed were controversial as this led to a decrease in adipogenic markers (Adipoq and PPARðŸ). Overall, disruption of FAM46A expression led to opposing changes in adipogenic potential, suggesting the requirement for a more stable cell system to study FAM46A in vitro. To further characterise the role of Fam46a, metabolic phenotyping of a Fam46a knockout (KO) mouse model under hyper-caloric stress was performed in collaboration with the IMG in Prague. This model revealed a significantly smaller mouse, and increased plasma alkaline phosphatase, as previously observed. When fed a high-fat diet, KO mice had reduced overall fat mass, improved glucose clearance and reduced adipocyte size in both subcutaneous and visceral white adipose tissue (subWAT/visWAT) depots. Transcriptomic analysis of these two depots revealed an up-regulation of genes expressed in ribosome related pathways in the subWAT, whereas the visWAT showed the up-regulation of fatty acid metabolism pathways, suggesting that the KO adipose tissue is more metabolically active. Other down-regulated pathways involved stem cell differentiation and BMP/TGFÎ²-signalling. In conclusion, this study found the possible regulation of the FAM46A promoter by TFs involved in adipogenesis regulation, such as SMAD proteins, as well as strengthening its possible functional involvement in TGFÎ² signalling by enrichment of this pathway in KO studies.

EPFL2021

Intraspecific trait variability mediates the response of subalpine grassland communities to extreme drought events

Vincent Jung, Thomas Spiegelberger

Climate change is expected to increase the magnitude and the frequency of extreme climatic events such as droughts. Better understanding how plant communities will respond to these droughts is a major challenge. We expect the response to be a shift in functional trait values resulting from both species turnover and intraspecific trait variability, but little research has addressed the relative contribution of both components. We analysed the short-term functional response of subalpine grassland communities to a simulated drought by focusing on four leaf traits (LDMC: leaf dry matter content, SLA: specific leaf area, LNC: leaf nitrogen concentration and LCC: leaf carbon concentration). After evaluating species turnover and intraspecific variability separately, we determined their relative contribution in the community functional response to drought, reflected by changes in community-weighted mean traits. We found significant species turnover and intraspecific variability, as well as significant changes in community-weighted mean for most of the traits. The relative contribution of intraspecific variability to the changes in community mean traits was more important (42-99%) than the relative contribution of species turnover (1-58%). Intraspecific variability either amplified (for LDMC, SLA and LCC) or dampened (for LNC) the community functional response mediated by species turnover. We demonstrated that the small contribution of species turnover to the changes in community mean LDMC and LCC was explained by a lack of covariation between species turnover and interspecific trait differences.Synthesis. These results highlight the need for a better consideration of intraspecific variability to understand and predict the effect of climate change on plant communities. While both species turnover and intraspecific variability can be expected following an extreme drought, we report new evidence that intraspecific variability can be a more important driver of the short-term functional response of plant communities.

Wiley-Blackwell2014

Variability of Muscle Synergies in Hand Grasps: Analysis of Intra- and Inter-Session Data

Una Pale

Background. Muscle synergy analysis is an approach to understand the neurophysiological mechanisms behind the hypothesized ability of the Central Nervous System (CNS) to reduce the dimensionality of muscle control. The muscle synergy approach is also used to evaluate motor recovery and the evolution of the patients’ motor performance both in single-session and longitudinal studies. Synergy-based assessments are subject to various sources of variability: natural trial-by-trial variability of performed movements, intrinsic characteristics of subjects that change over time (e.g., recovery, adaptation, exercise, etc.), as well as experimental factors such as different electrode positioning. These sources of variability need to be quantified in order to resolve challenges for the application of muscle synergies in clinical environments. The objective of this study is to analyze the stability and similarity of extracted muscle synergies under the effect of factors that may induce variability, including inter- and intra-session variability within subjects and inter-subject variability differentiation. The analysis was performed using the comprehensive, publicly available hand grasp NinaPro Database, featuring surface electromyography (EMG) measures from two EMG electrode bracelets. Methods. Intra-session, inter-session, and inter-subject synergy stability was analyzed using the following measures: variance accounted for (VAF) and number of synergies (NoS) as measures of reconstruction stability quality and cosine similarity for comparison of spatial composition of extracted synergies. Moreover, an approach based on virtual electrode repositioning was applied to shed light on the influence of electrode position on inter-session synergy similarity. Results. Inter-session synergy similarity was significantly lower with respect to intra-session similarity, both considering coefficient of variation of VAF (approximately 0.2–15% for inter vs. approximately 0.1% to 2.5% for intra, depending on NoS) and coefficient of variation of NoS (approximately 6.5–14.5% for inter vs. approximately 3–3.5% for intra, depending on VAF) as well as synergy similarity (approximately 74–77% for inter vs. approximately 88–94% for intra, depending on the selected VAF). Virtual electrode repositioning revealed that a slightly different electrode position can lower similarity of synergies from the same session and can increase similarity between sessions. Finally, the similarity of inter-subject synergies has no significant difference from the similarity of inter-session synergies (both on average approximately 84–90% depending on selected VAF). Conclusion. Synergy similarity was lower in inter-session conditions with respect to intra-session. This finding should be considered when interpreting results from multi-session assessments. Lastly, electrode positioning might play an important role in the lower similarity of synergies over different sessions.

2020