During range expansion, differences in traits can evolve between populations at the core and expanding edge of a range. While theory and experimental work have focused on range expansions across uniform environments, natural range expansions often occur over environmental gradients, which present novel selection pressures. We study phenotypic evolution at the core and edge of an active range expansion across an environmental gradient, and how adaptation may be constrained if the expression of genetic variation in novel environments is reduced. We focus on the timing of winter dormancy in a beetle (Diorhabda carinulata), expanding from northern areas with cold winters to southern areas with milder, shorter winters. We examine, first, the pattern of evolution of winter dormancy timing in core and edge environments, and second, how heritable genetic variation of a core population is expressed in local and edge environments. Phenotypes of core populations are consistent with adaptation to northern environments and maladaptation to southern ones. However, phenotypes of edge populations varied, indicating potential adaptation to more variable conditions across the southern sites. Clear shifts in phenotype at the expanding edge relative to the core suggest rapid evolution at the edge in response to southern climates. Heritability in a core population was high in a local environment but undetectable in a novel (edge) environment. These results show that core populations have adapted to their local environments, likely fueled by high heritability, but that long-distance movement into novel environments may reduce the heritable genetic variation on which selection can act, and thus hinder adaptation.

Orf virus (ORFV), a member of the Poxviridae family, causes contagious ecthyma (CE), a viral skin disease in small ruminants. Due to its self-limiting nature, low mortality rate and economic consequences, CE is considered as a neglected disease, resulting in underreporting in Thailand. Despite its global presence, the genetic characterization of ORFV in Thailand, especially in the southern region where there is high density of goat farming, is largely unknown. To address the knowledge gap, we conducted genetic and evolutionary analysis including phylogenetic, BEAST, and discriminant analysis of principal components (DAPC), on ORFV isolated from Southern Thailand, utilizing conserved B2L gene (major envelope protein) and A32L gene (C-terminal ATPase protein). All suspected CE meat goats across 2 farms in Songkhla and Pattani provinces in 2024 tested ORFV positive via PCR using ORFV-specific primers. These isolates along with a positive control isolate (Pattani 2020) were used for molecular characterization and genetic analysis. The 2024 isolates clustered with Malaysian strains based on phylogenetic and population analysis. BEAST analysis of these isolates further indicated a shared evolutionary origin around 2007, suggesting transboundary spread. Although the 2024 isolates were highly related, some differentiation observed for both genes and they evolved separately from 2020 Pattani isolate suggesting ongoing local evolution and genetic variation in the regional population. Moreover, the Pattani 2020 isolate was phylogenetically distinct and revealed a distinct ancestral origin, suggesting a separate introduction event into the region. Notably, heterogeneity in C-terminal region of ATPase gene was observed, including 4 amino acid deletions in Songkhla 2024 and Pattani 2020 isolates, and unique substitutions (G258S and G260S) in Pattani 2024 which may cause a distinct cluster based on DAPC analysis. Collectively, our findings indicate diverse ORFV evolution in Southern Thailand, necessitating continued molecular surveillance and genetic characterization to improve national control strategies.

The aim of the present study was to test the central-periphery hypothesis (CPH) of evolutionary genetics in terms of genetic diversity and differentiation in Alnus glutinosa (L.) Gaertn., 1790 and Picea abies (L.) H. Karst. populations. A total of 18 nuclear SSR loci were used to evaluate genetic diversity and differentiation of two rear-edge populations of each tree species from the south-eastern edges of their distribution ranges in Greece, and two populations of each species from the core distribution area in Lithuania. Peripheral populations of A. glutinosa exhibited high genetic diversity (mean Ar = 7.99, mean He = 0.72) and low genetic differentiation (peripheral and core population FST were 0.031 and 0.008, respectively). The genetic diversity values were even higher in the peripheral populations of P. abies (mean Ar = 12.27, mean He = 0.78), while genetic differentiation was also low (peripheral and core population FST was 0.013 and 0.011, respectively). Genetic differentiation between the peripheral and core regions was also low (FST = 0.038 and G″ST = 0.262 for A. glutinosa and FST = 0.023 and G″ST = 0.172 for P. abies). Observed heterozygosity was found to be higher in peripheral populations (0.80 on average for alder and 0.84 for spruce) than in core ones (0.72 and 0.83 on average for A. glutinosa and P. abies, respectively). On the other hand, expected heterozygosity was higher in A. glutinosa core populations than in its peripheral ones (0.73 vs. 0.72 on average for core and peripheral alder populations), while spruce populations were less heterozygous in the core area (0.78 vs. 0.75 on average for peripheral and core spruce populations, respectively). These results indicate only partial agreement with CPH. Rear-edge populations showed higher genetic differentiation, while their lower genetic diversity was not significantly different from that of core populations. The investigated rear-edge populations of A. glutinosa and P. abies present valuable genetic reserves of European importance. They show local adaptation and present ample genetic variation, and their effective population size will likely be sufficient for adaptive evolution in the future. Their long-term conservation status should be prioritized.

ABSTRACTPrevious epidemiological evidence has demonstrated that cheese, dried fruit, oily fish, and raw vegetables intake is inversely associated with the risk of cholelithiasis. Nevertheless, the underlying genetic mechanisms responsible for this relationship remain elusive, warranting a genomic‐level investigation into the molecular pathways mediating these associations. To investigate potential genetic linkages, genome‐wide association study (GWAS) datasets pertaining to cholelithiasis and four specific dietary patterns (cheese, dried fruit intake, oily fish, and raw vegetables) were employed within a multi‐stage analytical framework. Initially, genome‐wide genetic correlations were assessed through a combination of linkage disequilibrium score regression, genetic covariance analysis, and high‐definition likelihood methodologies. Concurrently, local genetic variation analyses were conducted to pinpoint relevant genomic loci. Mendelian randomization (MR) was employed to assess causal effects. Subsequently, conditional/conjunctional false discovery rate (cond/conjFDR) approaches were utilized to evaluate the genetic overlap between cholelithiasis and dietary traits. Integration of conjFDR with multi‐trait analysis of GWAS (MTAG) facilitated the identification of shared genetic loci. Significant inverse genome‐wide genetic correlations were identified between cholelithiasis and all four dietary patterns. Analyses of local genetic variation revealed overlapping genetic signals across several chromosomal regions. The application of cond/conjFDR approaches provided further validation of genetic commonality between the traits. Integration of conjFDR with MTAG led to the successful identification and validation of several key shared genetic loci. This investigation represents the first genomic‐level analysis establishing genetic associations between cholelithiasis and cheese, dried fruit intake, oily fish, and raw vegetable intake. The elucidated shared genetic loci offer novel molecular insights supporting dietary strategies for cholelithiasis prevention.

Abstract Introduction: Aberrant pre-mRNA splicing is a hallmark of many cancers, yet the underlying genetic mechanisms driving these alterations remain incompletely understood. While splice-altering variants can explain a subset of events, many tumor-specific splicing changes arise in the absence of nearby sequence variants. This study aims to systematically dissect the contribution of proximal splice-altering variants to tumor-specific splicing in pediatric brain tumors and to define the residual cohort likely driven by regulatory mechanisms such as mutations affecting splicing factors or the spliceosome machinery. We hypothesized that some fraction of tumor-specific splice events in pediatric brain tumors are not associated with nearby genetic variants, and that these may highlight broader disruptions to splicing regulation. Methods: We applied replicate Multivariate Analysis of Transcript Splicing (rMATS-turbo) to stranded total RNA-seq data (N=635) from the Pediatric Brain Tumor Atlas (PBTA). Tumor-specific single exon (SE) splicing events were defined as a change in percent spliced in (| ΔPSI |) > 0.3 between tumors and healthy brain samples sourced from GTEx (<40 years, n=2,642) and pediatric normals (n=7). Tumor-normal matched whole genome sequencing data were used to identify somatic and rare (<0.1% Allele Frequency in gnomad) germline SNVs/Indels proximal (<250nt) to rMATS-defined splice junctions. Results: Across the cohort (N=635), we identified 107,827 tumor-specific SE alternative splicing events. Only 44 tumors harbored a variant proximal to the affected splice site (11 germline, 39 somatic), leaving most events without a clear cause. We are now investigating this variant-negative subgroup as a preliminary cohort. Current efforts focus on excluding structural drivers before turning to potential regulatory mechanisms, including the disruption of spliceosome components. Preliminary findings suggest some tumors show altered expression or mutations in spliceosome components, though further validation is needed. Conclusion: This dual-ended analysis of tumor-specific splicing events reveals that while a subset can be attributed to local genetic variation, the majority likely arise from broader disruptions in splicing regulation. These findings underscore the importance of integrating RNA- and DNA-based analyses to fully capture the molecular basis of splicing dysregulation in cancer. Moreover, the variant-negative cohort may serve as a rich resource to uncover novel regulatory mechanisms and potential therapeutic targets in splicing-driven pediatric brain tumors. Citation Format: Patricia J Sullivan, Ryan J Corbett, Ammar S Naqvi, Alexander Sickler, Rebecca Kaufman, Bo Zhang, Chuwei Zhong, Sharon J Diskin, Jo Lynne Rokita. Uncovering genetic and regulatory drivers of tumor-specific splicing in pediatric brain tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Discovery and Innovation in Pediatric Cancer— From Biology to Breakthrough Therapies; 2025 Sep 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_2):Abstract nr B031.

Investigating genetic variability and differentiation in target populations of conservation concern is key, as poor genetic variability may further threaten their survival and persistence over time. Here we present the first genetic data for the Italian breeding population of the Montagu’s Harrier Circus pygargus, a declining migratory raptor species typical of steppe and agricultural landscapes, ranked as vulnerable at the national level. We analyzed four mitochondrial genes, the cytochrome oxidase gene (COXI), control region (D-loop), 16S RNA subunit gene (16S), and NADH dehydrogenase 2 gene (ND2), in six individuals from central Italy to estimate their phylogenetic relationships with European populations and assess local genetic variation. We recorded low genetic nucleotide diversity (π = 0.0009), but relatively high haplotype diversity (h = 0.8) compared to Central European populations and a close phylogenetic relationship of Italian Montagu’s Harriers with both western and eastern European populations. This study can serve as a baseline to study genetic variability and conservation of this vulnerable raptor species in Italy.

As organisms adapt to environmental changes, natural selection modifies the frequency of nonneutral alleles. For beneficial mutations, the outcome of this process may be a selective sweep, in which an allele rapidly increases in frequency and perhaps reaches fixation within a population. Selective sweeps have well-studied effects on patterns of local genetic variation in panmictic populations, but much less is known about the dynamics of sweeps in continuous space. In particular, because limited movement across a landscape leads to unique patterns of population structure, spatial dynamics may influence the trajectory of selected mutations. Here, we use forward-in-time, individual-based simulations in continuous space to study the impact of space on beneficial mutations as they sweep through a population. In particular, we show that selection changes the joint distribution of allele frequency and geographic range occupied by a focal allele and demonstrate that this signal can be used to identify selective sweeps. We then leverage this signal to identify in-progress selective sweeps within the malaria vector Anopheles gambiae, a species under strong selection pressure from vector control measures. By considering space, we identify multiple previously undescribed variants with potential phenotypic consequences, including mutations impacting known IR-associated genes and altering protein structure and properties. Our results demonstrate a novel signal for detecting selection in spatial population genetic data that may have implications for genomic surveillance and understanding geographic patterns of genetic variation.

Molecular characterization and phylogenetic analysis of babA gene of Helicobacter pylori isolated from Indian patients with gastrointestinal diseases

Gene expression is known to be affected by interactions between local genetic variation and DNA accessibility, with the latter organized into three-dimensional chromatin structures. Analyses of these interactions have previously been limited, obscuring their regulatory context, and the extent to which they occur throughout the genome. Here, we undertake a genome-scale analysis of these interactions in a genetically diverse population to systematically identify global genetic–epigenetic interaction, and reveal constraints imposed by chromatin structure. We establish the extent and structure of genotype-by-epigenotype interaction using embryonic stem cells derived from Diversity Outbred mice. This mouse population segregates millions of variants from eight inbred founders, enabling precision genetic mapping with extensive genotypic and phenotypic diversity. With 176 samples profiled for genotype, gene expression, and open chromatin, we used regression modeling to infer genetic–epigenetic interactions on a genome-wide scale. Our results demonstrate that statistical interactions between genetic variants and chromatin accessibility are common throughout the genome. We found that these interactions occur within the local area of the affected gene, and that this locality corresponds to topologically associated domains (TADs). The likelihood of interaction was most strongly defined by the three-dimensional (3D) domain structure rather than linear DNA sequence. We show that stable 3D genome structure is an effective tool to guide searches for regulatory elements and, conversely, that regulatory elements in genetically diverse populations provide a means to infer 3D genome structure. We confirmed this finding with CTCF ChIP-seq that revealed strain-specific binding in the inbred founder mice. In stem cells, open chromatin participating in the most significant regression models demonstrated an enrichment for developmental genes and the TAD-forming CTCF-binding complex, providing an opportunity for statistical inference of shifting TAD boundaries operating during early development. These findings provide evidence that genetic and epigenetic factors operate within the context of 3D chromatin structure.

Gene expression is known to be affected by interactions between local genetic variation and DNA accessibility, with the latter organized into three-dimensional chromatin structures. Analyses of these interactions have previously been limited, obscuring their regulatory context, and the extent to which they occur throughout the genome. Here, we undertake a genome-scale analysis of these interactions in a genetically diverse population to systematically identify global genetic-epigenetic interaction, and reveal constraints imposed by chromatin structure. We establish the extent and structure of genotype-by-epigenotype interaction using embryonic stem cells derived from Diversity Outbred mice. This mouse population segregates millions of variants from eight inbred founders, enabling precision genetic mapping with extensive genotypic and phenotypic diversity. With 176 samples profiled for genotype, gene expression, and open chromatin, we used regression modeling to infer genetic-epigenetic interactions on a genome-wide scale. Our results demonstrate that statistical interactions between genetic variants and chromatin accessibility are common throughout the genome. We found that these interactions occur within the local area of the affected gene, and that this locality corresponds to topologically associated domains (TADs). The likelihood of interaction was most strongly defined by the three-dimensional (3D) domain structure rather than linear DNA sequence. We show that stable 3D genome structure is an effective tool to guide searches for regulatory elements and, conversely, that regulatory elements in genetically diverse populations provide a means to infer 3D genome structure. We confirmed this finding with CTCF ChIP-seq that revealed strain-specific binding in the inbred founder mice. In stem cells, open chromatin participating in the most significant regression models demonstrated an enrichment for developmental genes and the TAD-forming CTCF-binding complex, providing an opportunity for statistical inference of shifting TAD boundaries operating during early development. These findings provide evidence that genetic and epigenetic factors operate within the context of 3D chromatin structure.

Extreme low pH events in estuaries and upwelling areas can modulate the phenotypic and genetic diversity of natural populations. To test this hypothesis, we explored the linkage between local scale extreme low pH events, genetic diversity, and variation in fecundity-related traits (body size, egg size, and egg production rate) in the broad-dispersal copepod Acartia tonsa. We assessed genetic and phenotypic characteristics of populations by contrasting extreme low pH environments (upwelling and temperate estuary) in the coastal Southeast Pacific, under natural and experimental conditions. These populations showed significant genetic differentiation with higher diversity in mitochondrial and nuclear loci (encoding mtCOI and 18S rRNA) in the estuarine population. Copepods from this population are exposed to more frequent extreme low pH events (< 7.7), and the adult females exhibit consistent phenotypic variation in body size, egg size, and egg production rate across different cohorts. Experimental acclimation to extreme low pH conditions revealed no significant differences in fecundity-related traits between A. tonsa populations. Although these results partially support our hypothesis, the experimental findings suggest other drivers might also influence phenotypic differences in the local environments.

Macrophyte habitats exhibit remarkable heterogeneity, encompassing the spatial variation of abiotic and biotic components such as changes in water conditions and weather as well as anthropogenic stressors. Environmental factors are thought to be important drivers shaping the genetic and epigenetic variation of aquatic plants. However, the links among genetic diversity, epigenetic variation, and environmental variables remain largely unclear, especially for clonal aquatic plants. Here, we performed population genetic and epigenetic analyses in conjunction with habitat discrimination to elucidate the environmental factors driving intraspecies genetic and epigenetic variation in hornwort (Ceratophyllum demersum) in a subtropical lake. Environmental factors were highly correlated with the genetic and epigenetic variation of C. demersum, with temperature being a key driver of the genetic variation. Lower temperature was detected to be correlated with greater genetic and epigenetic variation. Genetic and epigenetic variation were positively driven by water temperature, but were negatively affected by ambient air temperature. These findings indicate that the genetic and epigenetic variation of this clonal aquatic herb is not related to the geographic feature but is instead driven by environmental conditions, and demonstrate the effects of temperature on local genetic and epigenetic variation in aquatic systems.

Heavily urbanized areas can hinder dispersal and gene flow between amphibian populations. Given the growth potential of urbanization, it is important to examine how this specific environment shapes their genetic patterns at the local scale. The ability of the European green toad to successfully colonize large human settlements has been convincingly confirmed in the recent past, but little is known about its population genetics under these new conditions. In this study, we examined the effects of the environment on genetic variation, population structure, and the level of gene flow in populations of this amphibian in the city of Košice and the adjacent rural area (eastern Slovakia) using a set of neutral genetic markers. We found that urban populations had lower genetic variability than populations in adjacent rural areas; however, the degree of inbreeding was relatively low in all samples. Genetic differentiation was higher, and gene flow was more restricted in urban area, although geographic distances between sites were significantly less than in rural area (2–4 km versus 6–13 km). Our analyses suggested genetic isolation of urban populations at sites with less suitable habitat for green toads. In contrast, admixture of the population inhabiting the large city park, established on a former floodplain, with all rural populations was likely the result of an intense historical gene flow. The densely developed environment of the other urban sites likely presents a strong barrier to gene flow. The lack of suitable wetland habitat prior to development suggests that these sites were only recently colonized by a limited number of founders. Thus, we found differential effects of the city on the population structure of the green toad. Understanding current local genetic variation and structure is important for future conservation plans in urban environments.

Many genes are co‐expressed and form genomic domains of coordinated gene activity. However, the regulatory determinants of domain co‐activity remain unclear. Here, we leverage human individual variation in gene expression to characterize the co‐regulatory processes underlying domain co‐activity and systematically quantify their effect sizes. We employ transcriptional decomposition to extract from RNA expression data an expression component related to co‐activity revealed by genomic positioning. This strategy reveals close to 1,500 co‐activity domains, covering most expressed genes, of which the large majority are invariable across individuals. Focusing specifically on domains with high variability in co‐activity reveals that contained genes have a higher sharing of eQTLs, a higher variability in enhancer interactions, and an enrichment of binding by variably expressed transcription factors, compared to genes within non‐variable domains. Through careful quantification of the relative contributions of regulatory processes underlying co‐activity, we find transcription factor expression levels to be the main determinant of gene co‐activity. Our results indicate that distal trans effects contribute more than local genetic variation to individual variation in co‐activity domains.

Transvection, a type of trans-regulation of gene expression in which regulatory elements on one chromosome influence elements on a paired homologous chromosome, is itself a complex biological phenotype subject to modification by genetic background effects. However, relatively few studies have explored how transvection is affected by distal genetic variation, perhaps because it is strongly influenced by local regulatory elements and chromosomal architecture. With the emergence of the "hub" model of transvection and a series of studies showing variation in transvection effects, it is becoming clear that genetic background plays an important role in how transvection influences gene transcription. We explored the effects of genetic background on transvection by performing two independent genome wide association studies (GWASs) using the Drosophila genetic reference panel (DGRP) and a suite of Malic enzyme (Men) excision alleles. We found substantial variation in the amount of transvection in the 149 DGRP lines used, with broad-sense heritability of 0.89 and 0.84, depending on the excision allele used. The specific genetic variation identified was dependent on the excision allele used, highlighting the complex genetic interactions influencing transvection. We focussed primarily on genes identified as significant using a relaxed P-value cutoff in both GWASs. The most strongly associated genetic variant mapped to an intergenic single nucleotide polymorphism (SNP), located upstream of Tiggrin (Tig), a gene that codes for an extracellular matrix protein. Variants in other genes, such transcription factors (CG7368 and Sima), RNA binding proteins (CG10418, Rbp6, and Rig), enzymes (AdamTS-A, CG9743, and Pgant8), proteins influencing cell cycle progression (Dally and Eip63E) and signaling proteins (Atg-1, Axo, Egfr, and Path) also associated with transvection in Men. Although not intuitively obvious how many of these genes may influence transvection, some have been previously identified as promoting or antagonizing somatic homolog pairing. These results identify several candidate genes to further explore in the understanding of transvection in Men and in other genes regulated by transvection. Overall, these findings highlight the complexity of the interactions involved in gene regulation, even in phenotypes, such as transvection, that were traditionally considered to be primarily influenced by local genetic variation.

Simple SummaryThe risk of developing colorectal cancer (CRC) is partially associated with genetics. Different studies have provided valuable genetic information to understand the biology behind CRC and to build models of genetic risk. However, the study of the applicability of such genetic information within the Basque population is limited. Thus, our objectives were to find out if the genetic variants associated with CRC in other populations are the same in the Basque population and to assess the performance of the use of genetic information to calculate the risk of developing CRC. We found that the available genetic information can be applied to the Basque population, although local genetic variation can affect its use. Our findings will help to refine the use of CRC genetic risk calculation in the Basque population, and we expect that our findings could be useful for other populations.Although the genetic contribution to colorectal cancer (CRC) has been studied in various populations, studies on the applicability of available genetic information in the Basque population are scarce. In total, 835 CRC cases and 940 controls from the Basque population were genotyped and genome-wide association studies were carried out. Mendelian Randomization analyses were used to discover the effect of modifiable risk factors and microbiota on CRC. In total, 25 polygenic risk score models were evaluated to assess their performance in CRC risk calculation. Moreover, 492 inflammatory bowel disease cases were used to assess whether that genetic information would not confuse both conditions. Five suggestive (p < 5 × 10−6) loci were associated with CRC risk, where genes previously associated with CRC were located (e.g., ABCA12, ATIC or ERBB4). Moreover, the analyses of CRC locations detected additional genes consistent with the biology of CRC. The possible contribution of cholesterol, BMI, Firmicutes and Cyanobacteria to CRC risk was detected by Mendelian Randomization. Finally, although polygenic risk score models showed variable performance, the best model performed correctly regardless of the location and did not misclassify inflammatory bowel disease cases. Our results are consistent with CRC biology and genetic risk models and could be applied to assess CRC risk in the Basque population.

Inflammatory bowel disease (IBD) is characterised by chronic inflammation of the gastrointestinal tract. Although its aetiology remains unknown, environmental and genetic factors are involved in its development. Regarding genetics, more than 200 loci have been associated with IBD but the transferability of those signals to the Basque population living in Northern Spain, a population with distinctive genetic background, remains unknown. We have analysed 5,411,568 SNPs in 498 IBD cases and 935 controls from the Basque population. We found 33 suggestive loci (p < 5 × 10−6) in IBD and its subtypes, namely Crohn’s Disease (CD) and Ulcerative Colitis (UC), detecting a genome-wide significant locus located in HLA region in patients with UC. Those loci contain previously associated genes with IBD (IL23R, JAK2 or HLA genes) and new genes that could be involved in its development (AGT, BZW2 or FSTL1). The overall genetic correlation between European populations and Basque population was high in IBD and CD, while in UC was lower. Finally, the use of genetic risk scores based on previous GWAS findings reached area under the curves > 0.68. In conclusion, we report on the genetic architecture of IBD in the Basque population, and explore the performance of European-descent genetic risk scores in this population.

BackgroundGenome-wide association studies have identified statistical associations between various diseases, including cancers, and a large number of single-nucleotide polymorphisms (SNPs). However, they provide no direct explanation of the mechanisms underlying the association. Based on the recent discovery that changes in three-dimensional genome organization may have functional consequences on gene regulation favoring diseases, we investigated systematically the genome-wide distribution of disease-associated SNPs with respect to a specific feature of 3D genome organization: topologically associating domains (TADs) and their borders.ResultsFor each of 449 diseases, we tested whether the associated SNPs are present in TAD borders more often than observed by chance, where chance (i.e., the null model in statistical terms) corresponds to the same number of pointwise loci drawn at random either in the entire genome, or in the entire set of disease-associated SNPs listed in the GWAS catalog. Our analysis shows that a fraction of diseases displays such a preferential localization of their risk loci. Moreover, cancers are relatively more frequent among these diseases, and this predominance is generally enhanced when considering only intergenic SNPs. The structure of SNP-based diseasome networks confirms that localization of risk loci in TAD borders differs between cancers and non-cancer diseases. Furthermore, different TAD border enrichments are observed in embryonic stem cells and differentiated cells, consistent with changes in topological domains along embryogenesis and delineating their contribution to disease risk.ConclusionsOur results suggest that, for certain diseases, part of the genetic risk lies in a local genetic variation affecting the genome partitioning in topologically insulated domains. Investigating this possible contribution to genetic risk is particularly relevant in cancers. This study thus opens a way of interpreting genome-wide association studies, by distinguishing two types of disease-associated SNPs: one with an effect on an individual gene, the other acting in interplay with 3D genome organization.

Rye (Secale cereale ssp. cereale L.) is a secondary domesticate, considered to have originated as a weed in wheat fields and to have developed traits of domestication by evolving similar physiological and morphological characteristics to those of wheat. Although it migrated into Europe as a weed possessing domestication traits, it became one of the most significant crops grown in large parts of Europe from the medieval period onward. Within the modern borders of Germany, rye was grown using at least two divergent cultivation practices: eternal rye monoculture and three-field rotation. The straw of rye was used to produce Wellerhölzer, which are construction components in traditional half-timbered houses that have enabled a desiccated preservation of the plant remains. In order to assess the impact of cultivation practices, local environmental conditions and genetic variation on the genetic diversification of rye, we seek to integrate well-established archaeobotanical methods with aDNA sequencing of desiccated plant remains obtained from Wellerhölzer from Germany. In the current contribution, we present a proof of concept, based on the analysis of plant remains from a Wellerholz from the Old Town Hall of Göttingen. We use arable weed ecology to reconstruct cultivation practices and local environmental conditions and present a phylogenetic analysis based on targeted loci of the chloroplast and nuclear genome. Our results emphasise that the study of desiccated remains of plants from Wellerhölzer offer a unique opportunity for an integration of archaeobotanical reconstructions of cultivation practices and local environment and the sequencing of aDNA.

Abstract Expression QTL mapping provides information about genetic variant with modulatory effects on gene expression which are useful for understanding the genetic architecture of complex phenotypes. This mapping allows for uncovering of genomic regions associated with transcription regulation of genes which can be related to phenotypic variation when they colocalize with QTLs (cis and trans effects), providing a molecular basis for the phenotype-genotype association. The objectives of the present research were to perform eQTL mapping for meat quality traits in longissimus dorsi muscle and to uncover genes whose expression is influenced by local or distant genetic variation. A total of 120 steers from the University of Florida Beef Unit multibreed Angus-Brahman herd born between 2013 and 2014 were used in this study. The first three principal components from a principal component analysis for all meat quality phenotypes were used to construct a meat quality index. Eighty animals were selected based on extreme meat quality index for mRNA sequencing and 100 bp paired-end reads were mapped against to the Btau_4.6.1 reference genome. eQTL mapping was performed using 112,042 SNPs and 8,588 genes. A cis QTL was defined as an SNP located no more than 1 Mb upstream of the transcription start site or downstream of the transcription end site of an annotated gene. Polymorphisms associated with expression of at least 20 genes in the case of eQTL were considered hot spots. The harboring or adjacent gene was defined as master regulators. Multiple cis eQTLs and sQTLs effects were identified and genes such as LSM2, SOAT1, TTN and TEK are a few examples of potential expression and splicing regulatory genes. A total of 27 expression and 13 splicing master regulator genes were uncovered, mainly cytoskeletal or membrane-associated proteins, transcription factors and DNA methylases.