SEARCH · bioRxiv Science

Results for “genetics”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,513 records · Page 84Linked to original sources

bioRxiv2024

Associations between common genetic variants and income provide insights about the socioeconomic health gradient

We conducted a genome-wide association study (GWAS) on income among individuals of European descent and leveraged the results to investigate the socio-economic health gradient (N=668,288). We found 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes. Our GWAS-derived polygenic index captures 1 - 4% of income variance, with only one-fourth attributed to direct genetic effects. A phenome-wide association study using this polygenic index showed reduced risks for a broad spectrum of diseases, including hypertension, obesity, type 2 diabetes, coronary atherosclerosis, depression, asthma, and back pain. The income factor showed a substantial genetic correlation (0.92, s.e. = .006) with educational attainment (EA). Accounting for EAs genetic overlap with income revealed that the remaining genetic signal for higher income related to better mental health but reduced physical health benefits and increased participation in risky behaviours such as drinking and smoking.

genetics↗

bioRxiv2024

Quantitative genetics of natural S. cerevisiae strains upon sexual mating reveals heritable determinants of cellular fitness

Quantitative genetics requires large datasets of diverse phenotyped-genotyped strains from the same species. A special need is for such archived biological material and computerized data in sexually reproducing individuals from a species. Here we leverage sexual mating among close to 100 diverse natural isolates of the yeast S. cerevisiae that form about 4,000 hybrids combinations in several ecologically relevant growth conditions. In a first genetic study of this new resource we focus on fitness measurements and its modes of inheritance as a quantitative trait from parents to offspring hybrids. We employ genomic barcoding of all strains and a barcode recombination technique to follow hybrids of each successful mate combination. For all parents, and separately for all offspring hybrids we measure fitness under each condition. We focus on the inheritance of fitness, the ultimate evolutionary trait, and its inheritance as a quantitative trait upon sexual mating. Predicting hybrid fitness given parental parameters is a major challenge as it is likely multi-factorial. We find that hybrids fitness in fermentable carbon source correlates positively, yet modestly, with parental fitness, while on non-fermentable carbon, hybrid fitness shows no detectable correlation with parental fitness. Instead, the non-fermentable condition, hybrid fitness increases sharply with genetic distance between their parents, suggesting that outbreeding maximizes fitness irrespective of parental fitness at that condition. The number of minor alleles in the genome of each hybrid, analogous to polygenic risk score in classical genetics, negatively correlates with fitness in both conditions. Fitness inheritance can be explained by either a dominance or a co-dominance modes of inheritance, in the non-fermentable and fermentable conditions respectively. Our newly suggested biological resource and data provide new foundations for a quantitative research in genetics and evolution upon sexual mating. Furthermore, our barcoded strains and mating tracking method provide an important research resource for the yeast community.

genetics↗

bioRxiv2024

Genetic diversity within a tree and alternative indexes for different evolutionary effects

Trees, living for centuries, accumulate somatic mutations in their growing trunks and branches, causing genetic divergence within a single tree. Stem cell lineages in a shoot apical meristem accumulate mutations independently and diverge from each other. In plants, somatic mutations can alter the genetic composition of reproductive organs and gametes, impacting future generations. To evaluate the genetic variation among a trees reproductive organs, we consider three indexes: mean pairwise phylogenetic distance [Formula], phylogenetic diversity (PD; sum of branch lengths in molecular phylogeny), and parent-offspring phylogenetic distance (DPO). The tissue architecture of trees facilitated the accumulation of somatic mutations, which have various evolutionary effects, including enhancing fitness under strong sib competition and intense host-pathogen interactions, efficiently eliminating deleterious mutations through epistasis, and increasing genetic variance in the population. Choosing appropriate indexes for the genetic diversity of somatic mutations depends on the specific aspect of evolutionary influence being assessed.

genetics↗

bioRxiv2024

Complex genetic architecture underlying the plasticity of tobacco leaf width provides insight into across-environment genomic prediction

Phenotypic plasticity refers to the ability of a given genotype to produce multiple phenotypes in response to changing environmental conditions. Understanding the genetic basis of phenotypic plasticity and developing predictive models for agronomic traits are crucial for future agricultural adaptation to climate change. In this study, we investigated the genetic basis of leaf width mean (LWm) and plasticity (LWp) in a tobacco multiparent advanced generation inter-cross (MAGIC) population which consisting of 594 individuals. We identified 14 quantitative trait loci (QTLs) significantly associated with LWm, 43 with LWp. Our findings suggest that dynamic changes in QTL effects across environments, along with polygenic effects, may underlie the genetic basis of leaf width plasticity. Among them, qLW14 was narrowed down to a 3 Mb structural variation region. When this fragment was deleted in tobacco, plants exhibited increased leaf width, but only under specific environmental conditions. This finding suggests that the key gene within qLW14 may act as a negative regulator of leaf width through interactions with specific environmental factors. By integrating genetic diversity, environments variation, and their interactions into a GEAI model, we were able to build a framework for cross-environment prediction, improving prediction accuracy by 8.7% when compared to traditional model. Overall, this study highlights the complex genetic basis underlying LWp, involving multiple alleles and genotype-environment interactions. These findings provide valuable insights into the role of phenotypic plasticity in plant adaptation to environmental changes.

genetics↗

bioRxiv2024

Confounding of indirect genetic and epigenetic effects

An individuals phenotype reflects a complex interplay of the direct effects of their DNA, epigenetic modifications of their DNA induced by their parents, and indirect effects of their parents DNA. Here, we derive how the genetic variance within a population is changed under the influence of indirect maternal, paternal and parent-of-origin effects under random mating. We also consider indirect effects of a sibling, in particular how the genetic variance is altered when looking at the phenotypic difference between two siblings. The calculations are then extended to include assortative mating (AM), which alters the variance by inducing increased homozygosity and correlations within and across loci. AM likely leads to covariance of parental genetic effects, a measure of the similarity of parents in the indirect effects they have on their children. We propose that this assortment for parental characteristics, where biological parents create similar environments for their children, can create shared parental effects across traits and the appearance of cross-trait AM. Interestingly, the genetic variances is increased under AM for the childmother-father design, while it is decreased for the sibling difference. Our results demonstrate that it is not possible to get unbiased estimates of direct genetic effects without controlling for parental and parent-of-origin effects.

genetics↗

bioRxiv2024

Chromosome X Dosage Modulates Development of Aneuploidy in Genetically Diverse Mouse Embryonic Stem Cells

The genetic integrity of pluripotent stem cells (PSC) is critical to their applications in research and therapy, but it is compromised by frequent development of structural chromosome variants associated with malignancy. Many cell lines exhibit remarkable genetic stability, but little is known about the basis of the known variation in genomic integrity amongst different PSC isolates. Here we identify aneuploidies using RNA-seq and proteomics data from a panel of mouse embryonic stem cell (mESC) lines derived from 170 Diversity Outbred mice. We found 62 lines with detectable aneuploid subpopulations and a subset of originally XX lines that lost one Chromosome X (XO). Strikingly, a much lower proportion of XX lines were aneuploid, compared to XY or XO lines. Two single-cell RNA-seq data sets demonstrated that aneuploid XY DO mESC also show lower Chromosome X gene expression, and a prospective study confirmed that XY mESC accumulate higher aneuploid proportions in culture than isogenic XX lines. We identify potential mechanisms for this protective effect of X chromosome dosage, including our findings that the lines with two active X Chromosomes have a higher proportion of 2-cell-like cells, a state associated with maintenance of genetic integrity of mESC, and that they show differential expression of X-linked tumor suppressor genes associated with the DNA damage response. HighlightsO_LIFirst genetic analysis of predisposition to aneuploidy in pluripotent stem cell cultures C_LIO_LIChromosomal regions duplicated in aneuploid mouse embryonic stem cells are syntenic with regions overrepresented in human pluripotent stem cell lines bearing recurrent genetic abnormalities C_LIO_LIX-Chromosome dosage strongly influences susceptibility to aneuploidy in mouse embryonic stem cells and to a lesser degree in human pluripotent stem cells C_LIO_LIXX mouse embryonic stem cell lines show a higher proportion of cells in 2 cell-like state and higher expression of tumor suppressor genes associated with DNA damage response C_LI

genetics↗

bioRxiv2024

Hierarchical population genetic structure and signatures of adaptation in Lates calcarifer

ContextLates calcarifer is a widespread Indo-Pacific fish that is important in aquaculture, recreational and commercial fisheries. Genetic divergences from different data sources and sampling schemes have been reported. AimsTo conduct phylogenetic and population genetic analyses from a geographically and phylogenetically representative data set to identify hierarchical divisions within L. calcarifer. We further test the evolutionary significance of genetic units in terms of signatures of adaptation. MethodsUsing a whole-genome sequence data set of 61 fish including an outgroup, we conducted phylogenetic and population genetic analyes. We also generated measures of Fst, nucleotide diversity ({pi}) and Tajimas D (D). Key ResultsWe identify three main lineages of L. calcarifer corresponding to the Indian subcontinent, Southeast Asia and Australasia. Subdivision within each of the three main lineages is also identified and characterized. Adaptively significant differences are indicated within and between the three main lineages. ConclusionsL. calcarifer exhibits genetic divergences at different levels that originate before and during the Pleistocene. These divergences are associated with adaptive divergence but unclear phenotypic changes. ImplicationsThis study highlights the need for comprehensive sampling and integrative study of genotypes and phenotypes across the range of L. calcarifer.

genetics↗

bioRxiv2024

Not like other conifers: evaluation of phenotypic diversity in British common juniper, Juniperus communis, indicates genetic isolation and local adaptations among remnant populations

Habitat fragmentation and genetic isolation pose threats to the genetic diversity and resilience of natural populations. Protecting the genetic diversity of populations, and the processes that sustain it, optimises their ability to adapt to changing conditions and new threats: conservation efforts with this specific goal are known as "dynamic conservation." The common juniper, Juniperus communis, is a keystone species that provides habitat and resources for many plants and animals. It is a highly polymorphic species, and across its natural range it grows in a variety of habitats and growth forms. Juniper populations have been shrinking and becoming increasingly fragmented for over a century in the UK and elsewhere in Europe, raising concerns about the genetic diversity present in juniper populations and their ability to adapt to changing conditions, or their adaptive potential. This paper presents an analysis of the partitioning of phenotypic diversity among regions, populations and families from 16 UK populations assessed in a common garden trial. Our findings suggest high phenotypic variation among populations compared to the variation among families within populations, indicating barriers to gene flow between juniper populations, relatively homogenous populations and, consequently, potentially reduced adaptive potential. This information is a useful baseline for conservation managers and can also help to infer the genetic diversity and adaptive potential of populations.

genetics↗

bioRxiv2024

Understanding genetic diversity and phylogeography of Common Teal and its phylogenetic relationship with other water bird species in the wetlands of Kashmir Himalayas.

Understanding the genetic diversity and phylogeography of migratory species is critical for biodiversity conservation and the effective management of wetland ecosystems. The Kashmir Himalayas, an integral part of the Central Asian Flyway, host several key wetlands that provide critical wintering grounds for a variety of migratory birds. This study focuses on assessing the genetic characteristics and phylogenetic relationships of the Common Teal (Anas crecca) in comparison to other species within the families Anatidae and Rallidae. We analysed 149 blood samples, including 71 from A. crecca and 78 from other species in the two families, collected from wetlands in the Kashmir region. Using four mitochondrial markers--cytochrome oxidase subunit I (COI), cytochrome b (Cyt b), 16S rRNA, and the control region--we evaluated the genetic diversity and lineage connectivity of these species. Our findings reveal that the mitochondrial DNA haplotypes of A. crecca in the Kashmir Himalayas are shared with European populations, indicating strong maternal gene flow and connectivity between distant populations. A minimum spanning haplotype network analysis showed minimal nucleotide differences among haplotypes, particularly in the Cyt b and control regions, suggesting low genetic differentiation and a high degree of similarity among individuals. Notably, we identified at least four distinct maternal lineages of A. crecca in the Kashmir wetlands, reflecting diverse migratory sources. Our results also highlight that DNA barcoding using COI exhibited both high and low species resolution, with significant intraspecific variation, making it a valuable tool for further phylogeographic studies. The observed genetic diversity and haplotype sharing with distant populations underscore the ecological importance of Kashmirs wetlands as crucial habitats for migratory species. Our study emphasizes the need for targeted conservation and management strategies to preserve these vital ecosystems and the biodiversity they support.

genetics↗

bioRxiv2024

Multidimensional variable dose analysis (mVDA) is a novel method for high-throughput mapping of genetic interactions

The mapping of genetic interactions is a powerful tool to determine gene functions, assemble the structures of biological pathways and to identify therapeutic targets for disease. However, while there have been significant advances in the screening techniques used to identify genetic interactions over the past decade, methods that are sufficiently scalable to test genetic interactions on a genome level are still far from our current capabilities. Here, we describe an approach to genetic interaction screening in Drosophila cells that overcomes the scaling issues associated with most other methods. This method, called multidimensional Variable Dose Analysis (mVDA), allows multiple, random genes to be inhibited within each cell of a mixed population and the relative phenotypes caused by each gene or pair of genes to be deconvoluted. This means that reagent library size and cell population size do not scale exponentially with the number of genes to be tested, unlike previous methods. This method therefore has the potential to allow genome wide mapping of genetic interactions in Drosophila cells for the first time.

genetics↗

bioRxiv2024

Genetic Diversity of Hippophae rhamnoides Varieties with Different Fruit Characteristics

Hippophae rhamnoides is a valuable crop whose fruits are rich in bioactive compounds with health benefits. To date, there is a lack of genetic data for varieties of sea buckthorn. This fact hinders the identification of genetic determinants of valuable traits and limits the efficiency of breeding. In the present study, we analyzed a representative set of 55 valuable H. rhamnoides varieties of Russian breeding with different fruit characteristics and diverse lineages. Whole-genome sequencing was performed on the Illumina platform and at least 25x genome coverage was obtained for each accession. Based on the sequencing data, DNA polymorphisms were identified in genome regions corresponding to genes. These polymorphisms were used to evaluate the genetic relationships of the studied sea buckthorn varieties. We revealed genetically distinct groups of accessions that mostly corresponded to the lineages of the genotypes. Our data are important for assessing the effect of selection on sea buckthorn diversity and for evaluating the genetic relationship of different varieties, which is useful for breeders when selecting parental forms for crosses. The obtained information on DNA polymorphisms is also necessary to study the diversity of genes, including those that may determine valuable sea buckthorn traits, including fruit characteristics. Thus, our data can benefit both basic and applied research on sea buckthorn.

genetics↗

bioRxiv2025

Robustness of Selection and Timing Inference under Model Variation in Population Genetics

1In population genetics, accurately inferring the selection coefficient and the time of onset of advantageous mutations from genetic data is fundamental for understanding evolutionary processes. Here, we investigate how mismatches between the true evolutionary process and the inference model--specifically in the reproductive variance ({sigma}2) and the number of generations (L)--affect the posterior distributions of the selection coefficient and the time of onset. Using the Kolmogorov forward and backward equations, we model the stochastic dynamics of gene frequencies under selection and drift. We show that while the posterior distribution of the selection coefficient remains unaffected by changes in{sigma} 2 and L, this invariance does not apply to the time of onset. By framing the problem as a first passage time issue, we derive explicit expressions for the offsets in the posterior mean and variance of the time of onset that result from incorrect assumptions about{sigma} 2 and L. Our analysis reveals that these offsets are related to the mean and variance of the first passage time required for the allele frequency to reach a certain threshold, starting from an initial frequency determined by the model parameters. Under the assumption of a uniform prior for the time of onset, we find that the offset in the inferred mean is given by the difference in the effective generation duration ({Delta} = 1/{sigma}2) between the true process and the inference model. We validate our theoretical findings through simulations, demonstrating that the empirical offsets closely match our predictions. Furthermore, we generalize our results to accommodate non-uniform prior distributions, such as exponential priors, and provide numerical methods for calculating offsets under arbitrary priors. Stochastic fluctuations due to genetic drift, which are influenced by the reproductive variance and generational structure, can introduce significant biases in the posterior distribution of time of onset of advantageous mutations. By quantifying these biases, our framework enables more accurate adjustments to inferences drawn from genetic data, thereby enhancing our understanding of evolutionary dynamics and improving the reliability of population genetic analyses.

genetics↗

bioRxiv2025

The Role of Genetic Variation in Shaping Phenotypic Responses to Diet in Aging Drosophila melanogaster

Nutrition plays a central role in healthy living, however, extensive variability in individual responses to dietary interventions complicates our understanding of its effects. Here we present a comprehensive study utilizing the Drosophila Genetic Reference Panel (DGRP), investigating how genetic variation influences responses to diet and aging. Quantitative genetic analyses of the impact of dietary restriction on lifespan, locomotor activity, dry weight, and heat knockdown time were performed. Locomotor activity, dry weight and heat knockdown time were measured on the same individual flies. We found significant genotype-by-diet interaction (GDI) and genotype-by-age interaction (GAI) for all traits. Therefore, environmental factors play a crucial role in shaping trait variation at different ages and diets, and/or distinct genetic variation influences these traits at different ages and diets. Our genome wide association study also identified a quantitative trait locus for age-dependent dietary response. The observed GDI and GAI indicates that susceptibility to environmental influences changes as organisms age, which could have significant implications for dietary recommendations and interventions aimed at promoting healthy aging in humans. The identification of associations between DNA sequence variation and age-dependent dietary responses opens new avenues for research into the genetic mechanisms underlying these interactions.

genetics↗

bioRxiv2025

A Murine Database of Structural Variants Enables the Genetic Architecture of a Spontaneous Murine Lymphoma to be Characterized

A more complete map of the pattern of genetic variation among inbred mouse strains is essential for characterizing the genetic architecture of the many available mouse genetic models of important biomedical traits. Although structural variants (SVs) are a major component of genetic variation, they have not been adequately characterized among inbred strains due to methodological limitations. To address this, we generated high-quality long-read sequencing data for 40 inbred strains; and designed a pipeline to optimally identify and validate different types of SVs. This generated a database for 40 inbred strains with 573,191SVs, which included 10,815 duplications and 2,115 inversions, which also has 70 million SNPs and 7.5 million insertions/deletions. Analysis of this SV database identified an SV that is one component of a bi-genic model for lymphoma susceptibility in SJL mice, which provides mechanistic insight into the genetic basis for susceptibility to murine (and potentially human) lymphomas.

genetics↗

bioRxiv2025

Distinct Genetic Populations and Resistance Backgrounds of the Malaria Vector Anopheles funestus in Tanzania

Population genetic analysis of mosquitoes is becoming increasingly important for understanding the distribution of insecticide resistance alleles, devising sustainable insecticide-based vector control approaches, and how malaria vector populations are structured in space. Anopheles funestus is the dominant malaria vector in Tanzania and most parts of East and Southern Africa. To better understand its population genomic structure in Tanzania, we sequenced the genomes of 334 individual An. funestus mosquitoes from 11 administrative regions. We found two genetically differentiated populations; one inland and at high altitude (found in Katavi, Kagera, Kigoma, and Mwanza) and a second coastal, at low altitude (found in Pwani, Morogoro, Tanga, Ruvuma, Mtwara, Dodoma, and Lindi), with differences in genetic diversity and inbreeding. We found asynchronous selective sweeps, associated with insecticide resistance phenotypes, at the Cyp9k1 gene, and Cyp6p gene cluster, with distinct copy number-variant profiles between the coastal and inland populations. These results suggest that inland and coastal An. funestus populations have divergent histories, with the arid, central region of Tanzania, which also contains the Rift Valley being a possible barrier to gene flow. Such population disconnectedness should be considered for insecticide deployment, resistance management, and the rollout of novel genetic- based vector control approaches. These findings provide the most detailed study of Tanzanian An. funestus population structure and resistance genetics to date. Future research should examine the epidemiological relevance of this discontinuity in gene flow and whether these populations have different malaria transmission abilities.

genetics↗

bioRxiv2025

Wild and farmed Saccharina latissima in Europe: genetic insights for sustainable cultivation, traceability and environmental challenges

Kelp cultivation is expanding rapidly worldwide, although the aquaculture of Saccharina latissima (sugar kelp) in Europe remains in its early stages. However, major concerns have emerged about the potential impact of selected cultivars of the species on native populations of S. latissima which are already vulnerable to stressors including climate change. To address these concerns and support sustainable cultivation, it is essential to characterise genetic diversity and structure of wild kelp populations to monitor potential farm-to-wild gene flow. In this study we used 21 microsatellite loci to characterise the genetic structure of 24 natural and 3 farmed populations of S. latissima along European coasts. Results confirmed strong genetic differentiation between the northern and southern coasts, refining the boundaries between these two clusters compared to previous studies. Within each cluster, a clear genetic substructure was detected, with population differentiation being far more pronounced in the southern cluster. Cultivated sporophytes exhibited pedigrees that were all traced back to the local parent populations. Bayesian model-based structure analysis, discriminant analysis of principal components and assignment tests revealed no significant genetic differentiation between the farms and their wild populations. This indicates that farmed populations and neighbouring populations share the same gene pool, reflecting current cultivation practices. These findings contribute to understanding risks of gene flow between wild and farmed populations and demonstrate that strain traceability is feasible. Additionally, the study highlights the challenge European seaweed farmers face in securing reliable seedling stock, especially in the context of global change.

genetics↗

bioRxiv2025

Genetics in the ocean's twilight zone: Population structure of the Mueller's pearlside across its distribution range

The large estimates of mesopelagic fish biomass have fuelled harvesting interests in the relatively untouched oceans twilight zone. The Muellers pearlside, one of the most abundant species inhabiting the north Atlantic mesopelagic layer, is a candidate to such fisheries despite its enormous ecological importance and the insufficient knowledge about its population genetic structure. To shed light on the latter, 863 individuals sampled across the North Atlantic and Mediterranean were genotyped using 170 genome-wide SNPs. Analyses revealed habitat-driven differentiation in three units: Mediterranean Sea, oceanic samples, and Norwegian fjords. These groups were not completely isolated to each other as a cline of Mediterranean admixture was detected in the Eastern Atlantic facade up to 47{degrees}N in an otherwise genetically homogeneous oceanic cluster. Temperature seemed to modulate the differentiation patterns, and in the Mediterranean added to the complicated topography of the Greek Seas to shape genetic structure. In the Norwegian coastline, sills did not hamper genetic exchange among fjords ranging 200 km apart, probably due to the position of the species in the water column together with its swimming capacity. This genetic information should be combined with demographic properties to outline the management of this species prior to any eventual fishery attempt.

genetics↗

bioRxiv2025

Unravelling the genetic architecture of persistence in production, quality, and efficiency traits in laying hens at late production stages

BackgroundThe laying hen industry aims to extend production for the economic and environmental benefits it offers, while at the same time facing the challenges of declining egg production and quality in aging hens. To explore trait persistence, we studied 998 Rhode Island Red purebred hens from the Novogen nucleus. We recorded daily egg production from 70 to 92 weeks of age and measured individual feed intake twice a week for three weeks, starting at 70, 80, and 90 weeks, as well as body weight at the start and at the end of each feed intake recording period. Random regression models were used to study trait trajectories over time, and PCA and hierarchical clustering were applied to identify groups of hens based on estimated breeding values for the intercept and slope of traits trajectory. ResultsResults showed different aging trajectories among traits. Daily body weight variation, Feed conversion ratio, Haugh unit and yolk percentage showed persistence (i.e., stability) over the measured period. On the contrary, daily feed intake, residual feed intake, laying rate, egg mass, eggshell breaking strength and stiffness decreased over time, while body weight, mean egg weight and eggshell colour increased. To assess the feasibility of selecting for trait persistence, we estimated the genetic variance of the slope and its correlation with the intercept. We found that, for egg weight and eggshell colour, genetic variance of the slope was negligible, indicating that selection for persistence on these traits requires other means. On the contrary, the slope for other traits such as laying rate and residual feed intake showed significant additive genetic variance. Strong genetic correlations between trait estimates at different ages were also observed and heritabilities estimates were low to high depending of the traits and period. ConclusionThe study explores hens trait persistence from 70 to 92 weeks, suggesting potential for improved egg production persistence. Challenges arise from low genetic variances impacting the efficiency of the potential selection on persistence. Clustering analysis reveals distinctive response patterns to elongation of production and underlined that selecting for enhanced persistence of different traits will necessitate compromises in breeding goals.

genetics↗