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Background: Carcass weight (HCW) and marbling (MARB) are critical for meat quality and market value in beef cattle. In composite breeds like Brangus, which meld the genetics of Angus and Brahman, SNP-based analyses have illuminated some genetic influences on these traits, but they fall short in fully capturing the nuanced effects of breed of origin alleles (BOA) on these traits. Focus on the impacts of BOA on phenotypic features within Brangus populations can result in a more profound understanding of the specific influences of Angus and Brahman genetics. Moreover, the consideration of BOA becomes particularly significant when evaluating dominance effects contributing to heterosis in crossbred populations. BOA provides a more comprehensive measure of heterosis due to its ability to differentiate the distinct genetic contributions originating from each parent breed. This detailed understanding of genetic effects is essential for making informed breeding decisions to optimize the benefits of heterosis in composite breeds like Brangus. Objective: This study aims to identify quantitative trait loci (QTL) influencing HCW and MARB by utilizing SNP and BOA information, incorporating additive, dominance, and overdominance effects within a multi-generational Brangus commercial herd. Methods: We analyzed phenotypic data from 1,066 genotyped Brangus steers. BOA inference was performed using LAMP-LD software using Angus and Brahman reference sets. SNP-based and BOA-based GWAS were then conducted considering additive, dominance, and overdominance models. Results: The study identified numerous QTLs for HCW and MARB. A notable QTL for HCW was associated to the SGCB gene, pivotal for muscle growth, and was identified solely in the BOA GWAS. Several BOA GWAS QTLs exhibited a dominance effect underscoring their importance in estimating heterosis. Conclusions: Our findings demonstrate that SNP-based methods may not detect all genetic variation affecting economically important traits in composite breeds. BOA inclusion in genomic evaluations is crucial for identifying genetic regions contributing to trait variation and for understanding the dominance value underpinning heterosis. By considering BOA, we gain a deeper understanding of genetic interactions and heterosis, which is integral to advancing breeding programs. The incorporation of BOA is recommended for comprehensive genomic evaluations to optimize trait improvements in crossbred cattle populations. [ABSTRACT FROM AUTHOR]

Background: Heterosis breeding is one of the most important breeding methods for chrysanthemum. To date, the genetic mechanisms of heterosis for waterlogging tolerance in chrysanthemum are still unclear. This study aims to analyze the expression profiles and potential heterosis-related genes of two hybrid lines and their parents with extreme differences in waterlogging tolerance under control and waterlogging stress conditions by RNA-seq. Results: A population of 140 F1 progeny derived from Chrysanthemum indicum (Nanchang) (waterlogging-tolerant) and Chrysanthemum indicum (Nanjing) (waterlogging-sensitive) was used to characterize the extent of genetic variation in terms of seven waterlogging tolerance-related traits across two years. Lines 98 and 95, respectively displaying positive and negative overdominance heterosis for the waterlogging tolerance traits together with their parents under control and waterlogging stress conditions, were used for RNA-seq. In consequence, the maximal number of differentially expressed genes (DEGs) occurred in line 98. Gene ontology (GO) enrichment analysis revealed multiple stress-related biological processes for the common up-regulated genes. Line 98 had a significant increase in non-additive genes under waterlogging stress, with transgressive up-regulation and paternal-expression dominant patterns being the major gene expression profiles. Further, GO analysis identified 55 and 95 transgressive up-regulation genes that overlapped with the up-regulated genes shared by two parents in terms of responses to stress and stimulus, respectively. 6,640 genes in total displaying maternal-expression dominance patterns were observed in line 95. In addition, 16 key candidate genes, including SAP12, DOX1, and ERF017 which might be of significant importance for the formation of waterlogging tolerance heterosis in line 98, were highlighted. Conclusion: The current study provides a comprehensive overview of the root transcriptomes among F1 hybrids and their parents under waterlogging stress. These findings lay the foundation for further studies on molecular mechanisms underlying chrysanthemum heterosis on waterlogging tolerance. [ABSTRACT FROM AUTHOR]

Background: As a unique biological phenomenon, heterosis has been concerned with the superior performance of the heterosis than either parents. Despite several F1 hybrids, containing supernal nicotine content, had been discovered and applied to heterosis utilization in Nicotiana tabacum L., nevertheless, the potential molecular mechanism revealing nicotine heterosis has not been illustrated clearly. Result: Phenotypically, the F1 hybrids (Vall6 × Basma) show prominent heterosis in nicotine content by 3 years of field experiments. Transcriptome analysis revealed that genes participating in nicotine anabolism (ADC, PMT, MPO, QPT, AO, QS, QPT, A622, BBLs) and nicotine transport (JAT2, MATE1 and 2, NUP1 and 2) showed an upregulated expression in the hybrid, a majority of which demonstrated an overdominant performance. RT-PCR confirmed that nicotine anabolism was induced in the hybrid. Conclusions: These findings strongly suggest that nicotine synthesis and transport efficiency improved in hybrid and overdominance at gene-expression level played a critical role in heterosis of nicotine metabolism. [ABSTRACT FROM AUTHOR]

Background: Doherty and Zinkernagel, who discovered that antigen presentation is restricted by the major histocompatibility complex (MHC, called HLA in humans), hypothesized that individuals heterozygous at particular MHC loci might be more resistant to particular infectious diseases than the corresponding homozygotes because heterozygotes could present a wider repertoire of antigens. The superiority of heterozygotes over either corresponding homozygote, which we term allele-specific overdominance, is of direct biological interest for understanding the mechanisms of immune response; it is also a leading explanation for the observation that MHC loci are extremely polymorphic and that these polymorphisms have been maintained through extremely long evolutionary periods. Recent studies have shown that in particular viral infections, heterozygosity at HLA loci was associated with a favorable disease outcome, and such findings have been interpreted as supporting the allele-specific overdominance hypothesis in humans. Methods: An algebraic model is used to define the expected population-wide findings of an epidemiologic study of HLA heterozygosity and disease outcome as a function of allele-specific effects and population genetic parameters of the study population. Results: We show that overrepresentation of HLA heterozygotes among individuals with favorable disease outcomes (which we term population heterozygote advantage) need not indicate allele-specific overdominance. On the contrary, partly due to a form of confounding by allele frequencies, population heterozygote advantage can occur under a very wide range of assumptions about the relationship between homozygote risk and heterozygote risk. In certain extreme cases, population heterozygote advantage can occur even when every heterozygote is at greater risk of being a case than either corresponding homozygote. Conclusion: To demonstrate allele-specific overdominance for specific infections in human populations, improved analytic tools and/or larger studies (or studies in populations with limited HLA diversity) are necessary. [ABSTRACT FROM AUTHOR]

Background: Breeding rubber tree seedling with growth heterosis is vital for natural rubber production. It is the prerequisites for effectively utilizing growth heterosis to elucidate its molecular mechanisms, but the molecular mechanisms remain poorly understood in rubber tree. To elucidate seedling growth heterosis, we conducted comparative transcriptomic analyses between the two hybrids and their parents. Results: By identifying and comparing differently expressed genes (DEGs), we found that the hybrids (BT 3410 and WC 11) show significantly differential expression profiles from their parents (PR 107 and RRIM 600). In BT 3410-parent triad, 1092 (49.95%) and 1094 (50.05%) DEGs indicated clear underdominance or overdominance, respectively. Whereas in WC 11-parent triad, most DEGs (78.2%, 721) showed low- or high-parent dominance; 160 (17.35%) exhibited expression patterns that are not statistically distinguishable from additivity, and 8 (0.87%) and 33 (3.58%) DEGs exhibited underdominance and overdominance, respectively. Furthermore, some biological processes are differentially regulated between two hybrids. Interestingly, the pathway in response to stimulus is significantly downregulated and metabolic pathways are more highly regulated in BT 3410. Conclusions: Taken together, the genotypes, transcriptomes and biological pathways (especially, carbohydrate metabolism) are highly divergent between two hybrids, which may be associated with growth heterosis and weakness. Analyzing gene action models in hybrid-parent triads, we propose that overdominance may play important roles on growth heterosis, whereas dominance on hybrid weakness in rubber tree seedlings. These findings bring new insights into our understanding of growth heterosis of rubber tree seedling. [ABSTRACT FROM AUTHOR]

Background: The CACNA1C gene was defined as a risk gene for schizophrenia in a large genome-wide association study of European ancestry performed by the Psychiatric Genomics Consortium. Previous meta-analyses focused on the association between the CACNA1C gene rs1006737 and schizophrenia. The present study focused on whether there was an ancestral difference in the effect of the CACNA1C gene rs1006737 on schizophrenia. rs2007044 and rs4765905 were analyzed for their effect on the risk of schizophrenia. Methods: Pooled, subgroup, sensitivity, and publication bias analysis were conducted. Results: A total of 18 studies met the inclusion criteria, including fourteen rs1006737 studies (15,213 cases, 19,412 controls), three rs2007044 studies (6007 cases, 6518 controls), and two rs4765905 studies (2435 cases, 2639 controls). An allele model study also related rs2007044 and rs4765905 to schizophrenia. The overall meta-analysis for rs1006737, which included the allele contrast, dominant, recessive, codominance, and complete overdominance models, showed significant differences between rs1006737 and schizophrenia. However, the ancestral-based subgroup analysis for rs1006737 found that the genotypes GG and GG + GA were only protective factors for schizophrenia in Europeans. In contrast, the rs1006737 GA genotype only reduced the risk of schizophrenia in Asians. Conclusions: Rs1006737, rs2007044, and rs4765905 of the CACNA1C gene were associated with susceptibility to schizophrenia. However, the influence model for rs1006737 on schizophrenia in Asians and Europeans demonstrated both similarities and differences between the two ancestors. [ABSTRACT FROM AUTHOR]

Background: Genomic selection is an appealing method to select purebreds for crossbred performance. In the case of crossbred records, single nucleotide polymorphism (SNP) effects can be estimated using an additive model or a breed-specific allele model. In most studies, additive gene action is assumed. However, dominance is the likely genetic basis of heterosis. Advantages of incorporating dominance in genomic selection were investigated in a two-way crossbreeding program for a trait with different magnitudes of dominance. Training was carried out only once in the simulation. Results: When the dominance variance and heterosis were large and overdominance was present, a dominance model including both additive and dominance SNP effects gave substantially greater cumulative response to selection than the additive model. Extra response was the result of an increase in heterosis but at a cost of reduced purebred performance. When the dominance variance and heterosis were realistic but with overdominance, the advantage of the dominance model decreased but was still significant. When overdominance was absent, the dominance model was slightly favored over the additive model, but the difference in response between the models increased as the number of quantitative trait loci increased. This reveals the importance of exploiting dominance even in the absence of overdominance. When there was no dominance, response to selection for the dominance model was as high as for the additive model, indicating robustness of the dominance model. The breed-specific allele model was inferior to the dominance model in all cases and to the additive model except when the dominance variance and heterosis were large and with overdominance. However, the advantage of the dominance model over the breed-specific allele model may decrease as differences in linkage disequilibrium between the breeds increase. Retraining is expected to reduce the advantage of the dominance model over the alternatives, because in general, the advantage becomes important only after five or six generations post-training. Conclusion: Under dominance and without retraining, genomic selection based on the dominance model is superior to the additive model and the breed-specific allele model to maximize crossbred performance through purebred selection. [ABSTRACT FROM AUTHOR]

Background: Plant height (PH) and ear height (EH) are two important agronomic traits in maize selection breeding. F1 hybrid exhibit significant heterosis for PH and EH as compared to their parental inbred lines. To understand the genetic basis of heterosis controlling PH and EH, we conducted quantitative trait locus (QTL) analysis using a recombinant inbreed line (RIL) based design III population derived from the elite maize hybrid Zhengdan 958 in five environments. Results: A total of 14 environmentally stable QTLs were identified, and the number of QTLs for Z1 and Z2 populations was six and eight, respectively. Notably, all the eight environmentally stable QTLs for Z2 were characterized by overdominance effect (OD), suggesting that overdominant QTLs were the most important contributors to heterosis for PH and EH. Furthermore, 14 environmentally stable QTLs were anchored on six genomic regions, among which four are trait-specific QTLs, suggesting that the genetic basis for PH and EH is partially different. Additionally, qPH.A-1.3, modifying about 10 centimeters of PH, was further validated in backcross populations. Conclusions: The genetic basis for PH and EH is partially different and overdominant QTLs are important factors for heterosis of PH and EH. A major QTL qPH.A-1.3 may be a desired target for genetic improvement of maize plant height. [ABSTRACT FROM AUTHOR]

Background: The four casein proteins in goat milk are encoded by four closely linked casein loci (CSN1S1, CSN2, CSN1S2 and CSN3) within 250 kb on caprine chromosome 6. A deletion in exon 12 of CSN1S1, so far reported only in Norwegian goats, has been found at high frequency (0.73). Such a high frequency is difficult to explain because the national breeding goal selects against the variant's effect. Methods: In this study, 575 goats were genotyped for 38 Single Nucleotide Polymorphisms (SNP) located within the four casein genes. Milk production records of these goats were obtained from the Norwegian Dairy Goat Control. Test-day mixed models with additive and dominance fixed effects of single SNP were fitted in a model including polygenic effects. Results: Significant additive effects of single SNP within CSN1S1 and CSN3 were found for fat % and protein %, milk yield and milk taste. The allele with the deletion showed additive and dominance effects on protein % and fat %, and overdominance effects on milk quantity (kg) and lactose %. At its current frequency, the observed dominance (overdominance) effects of the deletion allele reduced its substitution effect (and additive genetic variance available for selection) in the population substantially. Conclusions: The selection pressure of conventional breeding on the allele with the deletion is limited due to the observed dominance (overdominance) effects. Inclusion of molecular information in the national breeding scheme will reduce the frequency of this deletion in the population. [ABSTRACT FROM AUTHOR]

Background: Estimating the genetic component of a complex phenotype is a complicated problem, mainly because there are many allele effects to estimate from a limited number of phenotypes. In spite of this difficulty, linear methods with variable selection have been able to give good predictions of additive effects of individuals. However, prediction of non-additive genetic effects is challenging with the usual prediction methods. In machine learning, non-additive relations between inputs can be modeled with neural networks. We developed a novel method (NetSparse) that uses Bayesian neural networks with variable selection for the prediction of genotypic values of individuals, including non-additive genetic effects. Results: We simulated several populations with different phenotypic models and compared NetSparse to genomic best linear unbiased prediction (GBLUP), BayesB, their dominance variants, and an additive by additive method. We found that when the number of QTL was relatively small (10 or 100), NetSparse had 2 to 28 percentage points higher accuracy than the reference methods. For scenarios that included dominance or epistatic effects, NetSparse had 0.0 to 3.9 percentage points higher accuracy for predicting phenotypes than the reference methods, except in scenarios with extreme overdominance, for which reference methods that explicitly model dominance had 6 percentage points higher accuracy than NetSparse. Conclusions: Bayesian neural networks with variable selection are promising for prediction of the genetic component of complex traits in animal breeding, and their performance is robust across different genetic models. However, their large computational costs can hinder their use in practice. [ABSTRACT FROM AUTHOR]

Nicotine exhibits obvious heterosis, which can be used to create Nicotiana tabacum L. (tobacco) varieties with varying nicotine content. However, the reasons for the formation of nicotine heterosis and its relationship to nicotine transport and accumulation remain unknown. This study conducted a comprehensive analysis of six tobacco hybrids with varying heterosis levels and their parent materials from various aspects, such as phenotype, physiology, and transcriptomics. The results showed that the direct path coefficient of transport heterosis to nicotine heterosis was highest in hybrids, at 0.98, and a highly significant positive correlation between the two. The plant height, thick stalk circumference, large flow of tissue fluid in the stalk, and high nicotine concentration of tobacco were the underlying factors that led to the strong nicotine transport capacity of hybrids. The formation of nicotine transport heterosis in hybrids was mainly influenced by non-additive gene effects (accounting for 89.93%), with over-dominant effects playing a dominant role (accounting for 58.79%). Among non-additive expression DEGs, nicotine transporter related multi antimicrobial extrusion protein, drug/metabolite transporter, ABC family transporter, and glutathione S-transferase were significantly upregulated in hybrid strains. The RT-qPCR results indicated that these genes related nicotine transport also exhibited heterosis at the expression level. Our results revealed that the formation of nicotine heterosis is mainly achieved by enhancing the nicotine transport capacity in hybrids. The results are not only beneficial for promoting the theoretical study of nicotine heterosis in tobacco and the breeding and utilization of hybrids, but are also of great significance for guiding nicotine production and promoting its multipurpose utilization. [ABSTRACT FROM AUTHOR]

Background: The additive model of inheritance assumes that heterozygotes (Aa) are exactly intermediate in respect to homozygotes (AA and aa). While this model is commonly used in single-locus genetic association studies, significant deviations from additivity are well-documented and contribute to phenotypic variance across many traits and systems. This assumption can introduce type I and type II errors by overestimating or underestimating the effects of variants that deviate from additivity. Alternative genotype encoding strategies have been explored to account for different inheritance patterns, but they often incur significant computational or methodological costs. To address these challenges, we introduce PAGER (Phenotype Adjusted Genotype Encoding and Ranking), an efficient pre-processing method that encodes each genetic variant based on normalized mean phenotypic differences between diallelic genotype classes (AA, Aa, and aa). This approach more accurately reflects each variant's true inheritance model, improving model precision while minimizing the costs associated with alternative encoding strategies. Results: Through extensive benchmarking on SNPs simulated with both binary and continuous phenotypes, we demonstrate that PAGER accurately represents various inheritance patterns (including additive, dominant, recessive, and heterosis), achieves levels of statistical power that meet or exceed other encoding strategies, and attains computation speeds up to 55 times faster than a similar method, EDGE. We also apply PAGER to publicly available real-world data and identify a novel, relevant putative QTL associated with body mass index in rats (Rattus norvegicus) that is not detected with the additive model. Conclusions: Overall, we show that PAGER is an efficient genotype encoding approach that can uncover sources of missing heritability and reveal novel insights in the study of complex traits while incurring minimal costs. [ABSTRACT FROM AUTHOR]

Switchgrass (Panicum virgatum L.) is a perennial C4 warm-season grass known for its high-biomass yield and wide environmental adaptability, making it an ideal bioenergy crop. Despite its potential, switchgrass seedlings grow slowly, often losing out to weeds in field conditions and producing limited biomass in the first year of planting. Furthermore, during the reproductive growth stage, the above-ground biomass rapidly increases in lignin content, creating a significant saccharification barrier. Previous studies have identified rhythm-related genes TOC1 and LHY as crucial to the slow seedling development in switchgrass, yet the precise regulatory functions of these genes remain largely unexplored. In this study, the genes TOC1 and LHY were characterized within the tetraploid genome of switchgrass. Gene expression analysis revealed that PvTOC1 and PvLHY exhibit circadian patterns under normal growth conditions, with opposing expression levels over time. PvTOC1 genes were predominantly expressed in florets, vascular bundles, and seeds, while PvLHY genes showed higher expression in stems, leaf sheaths, and nodes. Overexpression of PvTOC1 from the N chromosome group (PvTOC1-N) or PvLHY from the K chromosome group (PvLHY-K) in Arabidopsis thaliana led to alterations in circadian rhythm and hormone metabolism, resulting in shorter roots, delayed flowering, and decreased resistance to oxidative stress. These transgenic lines exhibited reduced sensitivity to hormones and hormone inhibitors, and displayed altered gene expression in the biosynthesis and signal transduction pathways of abscisic acid (ABA), gibberellin (GA), 3-indoleacetic acid (IAA), and strigolactone (SL). These findings highlight roles of PvTOC1-N and PvLHY-K in plant development and offer a theoretical foundation for genetic improvements in switchgrass and other crops. [ABSTRACT FROM AUTHOR]

Background: Epistasis, the interaction between genetic loci where the effect of one locus is influenced by one or more other loci, plays a crucial role in the genetic architecture of complex traits. However, as the number of loci considered increases, the investigation of epistasis becomes exponentially more complex, making the selection of key features vital for effective downstream analyses. Relief-Based Algorithms (RBAs) are often employed for this purpose due to their reputation as "interaction-sensitive" algorithms and uniquely non-exhaustive approach. However, the limitations of RBAs in detecting interactions, particularly those involving multiple loci, have not been thoroughly defined. This study seeks to address this gap by evaluating the efficiency of RBAs in detecting higher-order epistatic interactions. Motivated by previous findings that suggest some RBAs may rank predictive features involved in higher-order epistasis negatively, we explore the potential of absolute value ranking of RBA feature weights as an alternative approach for capturing complex interactions. In this study, we assess the performance of ReliefF, MultiSURF, and MultiSURFstar on simulated genetic datasets that model various patterns of genotype-phenotype associations, including 2-way to 5-way genetic interactions, and compare their performance to two control methods: a random shuffle and mutual information. Results: Our findings indicate that while RBAs effectively identify lower-order (2 to 3-way) interactions, their capability to detect higher-order interactions is significantly limited, primarily by large feature count but also by signal noise. Specifically, we observe that RBAs are successful in detecting fully penetrant 4-way XOR interactions using an absolute value ranking approach, but this is restricted to datasets with only 20 total features. Conclusions: These results highlight the inherent limitations of current RBAs and underscore the need for the development of Relief-based approaches with enhanced detection capabilities for the investigation of epistasis, particularly in datasets with large feature counts and complex higher-order interactions. [ABSTRACT FROM AUTHOR]

Heterosis, recognized for improving crop performance, especially in the first filial (F1) generation, remains an area of significant study in the tobacco industry. The low utilization of leaf veins in tobacco contributes to economic inefficiency and resource waste. Despite the positive impacts of heterosis on crop genetics, investigations into leaf-vein ratio heterosis in tobacco have been lacking. Understanding the mechanisms underlying negative heterosis in leaf vein ratio at the molecular level is crucial for advancing low vein ratio leaf breeding research. This study involved 12 hybrid combinations and their parental lines to explore heterosis associated with leaf vein ratios. The hybrids displayed diverse patterns of positive or negative leaf vein ratio heterosis across different developmental stages. Notably, the F1 hybrid (G70 × Qinggeng) consistently exhibited substantial negative heterosis, reaching a maximum of -19.79% 80 days after transplanting. A comparative transcriptome analysis revealed that a significant proportion of differentially expressed genes (DEGs), approximately 39.04% and 23.73%, exhibited dominant and over-dominant expression patterns, respectively. These findings highlight the critical role of non-additive gene expression, particularly the dominance pattern, in governing leaf vein ratio heterosis. The non-additive genes, largely associated with various GO terms such as response to abiotic stimuli, galactose metabolic process, plant-type cell wall organization, auxin-activated signaling pathway, hydrolase activity, and UDP-glycosyltransferase activity, were identified. Furthermore, KEGG enrichment analysis unveiled their involvement in phenylpropanoid biosynthesis, galactose metabolism, plant hormone signal transduction, glutathione metabolism, MAPK signaling pathway, starch, and sucrose metabolism. Among the non-additive genes, we identified some genes related to leaf development, leaf size, leaf senescence, and cell wall extensibility that showed significantly lower expression in F1 than in its parents. These results indicate that the non-additive expression of genes plays a key role in the heterosis of the leaf vein ratio in tobacco. This study marks the first exploration into the molecular mechanisms governing leaf vein ratio heterosis at the transcriptome level. These findings significantly contribute to understanding leaf vein ratios in tobacco breeding strategies. [ABSTRACT FROM AUTHOR]

Background: Productive life (PL) of a cow is the time the cow remains in the milking herd from first calving to exit from the herd due to culling or death and is an important economic trait in U.S. Holstein cattle. The large samples of Holstein genomic evaluation data that have become available recently provided unprecedented statistical power to identify genetic factors affecting PL in Holstein cows using the approach of genome-wide association study (GWAS). Methods: The GWAS analysis used 1,103,641 Holstein cows with phenotypic observations on PL and genotypes of 75,282 single nucleotide polymorphism (SNP) markers. The statistical tests and estimation of SNP additive and dominance effects used the approximate generalized least squares method implemented by the EPISNPmpi computer program. Results: The GWAS detected 5390 significant additive effects of PL distributed over all 29 autosomes and the X–Y nonrecombining region of the X chromosome (Chr31). Two chromosome regions had the most significant and largest cluster of additive effects, the SLC4A4-GC-NPFFR2 (SGN) region of Chr06 with pleiotropic effects for PL, fertility, somatic cell score and milk yield; and the 32–52 Mb region of Chr10 with peak effects for PL in or near RASGRP1 with many important immunity functions. The dominance tests detected 38 significant dominance effects including 12 dominance effects with sharply negative homozygous recessive genotypes on Chr18, Chr05, Chr23 and Chr24. Conclusions: The GWAS results showed that highly significant genetic effects for PL were in chromosome regions known to have highly significant effects for fertility and health and a chromosome region with multiple genes with reproductive and immunity functions. SNPs with rare but sharply negative homozygous recessive genotypes for PL existed and should be used for eliminating heifers carrying those homozygous recessive genotypes. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD. Methods: Five TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk. Results: Model association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P < 0.001), and the MR analysis revealed an association between short LTL and an elevated risk of CSVD. PRS-based genetic prediction of short LTLs was also significantly related to an elevated CSVD risk. Conclusion: Multiple genetic models and MR results indicate that TERT gene SNPs may be related to an elevated risk of CSVD, and that shorter LTL may be causally linked to such CSVD risk. [ABSTRACT FROM AUTHOR]

Background: Pyrethroid resistance is one of the major threats for effectiveness of insecticide-treated bed nets (ITNs) in malaria vector control. Genotyping of mutations in the voltage gated sodium channel (VGSC) gene is widely used to easily assess the evolution and spread of pyrethroid target-site resistance among malaria vectors. L1014F and L1014S substitutions are the most common and best characterized VGSC mutations in major African malaria vector species of the Anopheles gambiae complex. Recently, an additional substitution involved in pyrethroid resistance, i.e. V402L, has been detected in Anopheles coluzzii from West Africa lacking any other resistance alleles at locus 1014. The evolution of target-site resistance mutations L1014F/S and V402L was monitored in An. coluzzii and Anopheles arabiensis specimens from a Burkina Faso village over a 10-year range after the massive ITN scale-up started in 2010. Methods: Anopheles coluzzii (N = 300) and An. arabiensis (N = 362) specimens collected both indoors and outdoors by different methods (pyrethrum spray catch, sticky resting box and human landing collections) in 2011, 2015 and 2020 at Goden village were genotyped by TaqMan assays and sequencing for the three target site resistance mutations; allele frequencies were statistically investigated over the years. Results: A divergent trend in resistant allele frequencies was observed in the two species: 1014F decreased in An. coluzzii (from 0.76 to 0.52) but increased in An. arabiensis (from 0.18 to 0.70); 1014S occurred only in An. arabiensis and slightly decreased over time (from 0.33 to 0.23); 402L increased in An. coluzzii (from 0.15 to 0.48) and was found for the first time in one An. arabiensis specimen. In 2020 the co-occurrence of different resistance alleles reached 43% in An. coluzzii (alleles 410L and 1014F) and 32% in An. arabiensis (alleles 1014F and 1014S). Conclusions: Overall, an increasing level of target-site resistance was observed among the populations with only 1% of the two malaria vector species being wild type at both loci, 1014 and 402, in 2020. This, together with the co-occurrence of different mutations in the same specimens, calls for future investigations on the possible synergism between resistance alleles and their phenotype to implement local tailored intervention strategies. [ABSTRACT FROM AUTHOR]

Soybean represents a vital source of premium plant-based proteins for human nutrition. Importantly, the level of water-soluble protein (WSP) is crucial for determining the overall quality and nutritional value of such crops. Enhancing WSP levels in soybean plants is a high-priority goal in crop improvement. This study aimed to elucidate the genetic basis of WSP content in soybean seeds by identifying quantitative trait loci (QTLs) and set the foundation for subsequent gene cloning and functional analysis. Using 180 F10 recombinant inbred lines generated by crossing the high-protein soybean cultivar JiDou 12 with the wild variety Ye 9, our researcher team mapped the QTLs influencing protein levels, integrating Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene expression profiling to identify candidate genes. During the 2020 and 2022 growing seasons, a standard bell-shaped distribution of protein content trait data was observed in these soybean lines. Eight QTLs affecting protein content were found across eight chromosomes, with LOD scores ranging from 2.59 to 7.30, explaining 4.15–11.74% of the phenotypic variance. Notably, two QTLs were newly discovered, one with a elite allele at qWSPC-15 from Ye 9. The major QTL, qWSPC-19, on chromosome 19 was stable across conditions and contained genes involved in nitrogen metabolism, amino acid biosynthesis, and signaling. Two genes from this QTL, Glyma.19G185700 and Glyma.19G186000, exhibited distinct expression patterns at maturity, highlighting the influence of these genes on protein content. This research revealed eight QTLs for WSP content in soybean seeds and proposed a gene for the key QTL qWSPC-19, laying groundwork for gene isolation and enhanced soybean breeding through the use of molecular markers. These insights are instrumental for developing protein-rich soybean cultivars. [ABSTRACT FROM AUTHOR]

Background: Inter-subspecific hybrid rice represents a significant breakthrough in agricultural genetics, offering higher yields and better resilience to various environmental stresses. While the utilization of these hybrids has shed light on the genetic processes underlying hybridization, understanding the molecular mechanisms driving heterosis remains a complex and ongoing challenge. Here, chromatin immunoprecipitation-sequencing (ChIP-seq) was used to analyze genome-wide profiles of H3K4me3 and H3K27me3 modifications in the inter-subspecific hybrid rice ZY19 and its parents, Z04A and ZHF1015, then combined them with the transcriptome and DNA methylation data to uncover the effects of histone modifications on gene expression and the contribution of epigenetic modifications to heterosis. Results: In the hybrid, there were 8,126 and 1,610 different peaks for H3K4me3 and H3K27me3 modifications when compared to its parents, respectively, with the majority of them originating from the parental lines. The different modifications between the hybrid and its parents were more frequently observed as higher levels in the hybrid than in the parents. In ZY19, there were 476 and 84 allele-specific genes with H3K4me3 and H3K27me3 modifications identified, representing 7.9% and 12% of the total analyzed genes, respectively. Only a small portion of genes that showed differences in parental H3K4me3 and H3K27me3 modifications which demonstrated allele-specific histone modifications (ASHM) in the hybrid. The H3K4me3 modification level in the hybrid was significantly lower compared to the parents. In the hybrid, DNA methylation occurs more frequently among histone modification target genes. Additionally, over 62.58% of differentially expressed genes (DEGs) were affected by epigenetic variations. Notably, there was a strong correlation observed between variations in H3K4me3 modifications and gene expression levels in the hybrid and its parents. Conclusion: These findings highlight the substantial impact of histone modifications and DNA methylation on gene expression during hybridization. Epigenetic variations play a crucial role in controlling the differential expression of genes, with potential implications for heterosis. [ABSTRACT FROM AUTHOR]

Background: The transition from vegetative to reproductive growth is a key factor in yield maximization. Sesame (Sesamum indicum), an indeterminate short-day oilseed crop, is rapidly being introduced into new cultivation areas. Thus, decoding its flowering mechanism is necessary to facilitate adaptation to environmental conditions. In the current study, we uncover the effect of day-length on flowering and yield components using F 2 populations segregating for previously identified quantitative trait loci (Si_DTF QTL) confirming these traits. Results: Generally, day-length affected all phenotypic traits, with short-day preceding days to flowering and reducing yield components. Interestingly, the average days to flowering required for yield maximization was 50 to 55 days, regardless of day-length. In addition, we found that Si_DTF QTL is more associated with seed-yield and yield components than with days to flowering. A bulk-segregation analysis was applied to identify additional QTL differing in allele frequencies between early and late flowering under both day-length conditions. Candidate genes mining within the identified major QTL intervals revealed two flowering-related genes with different expression levels between the parental lines, indicating their contribution to sesame flowering regulation. Conclusions: Our findings demonstrate the essential role of flowering date on yield components and will serve as a basis for future sesame breeding. [ABSTRACT FROM AUTHOR]

Background: A greater experience of "social safeness" in social relationships has been associated with reduced general psychopathology. This association appears to be independent of the perceived level of actual social support. The tripartite model of emotion suggests that experiences of social safeness may be associated with increased activation of the 'soothing system', inhibiting the experience of threat and shame. Associations of eating disorder (ED) pathology and shame have been well established. This study aims to answer the questions: Is there an association with experience of social safeness and ED symptoms in a non-clinical sample? Are any associations independent of perceived or received social support? Methods: A non-clinical sample of 80 young adults (aged 18–25) completed an online survey. The survey included measures of ED symptoms, social safeness, perceived and received social support and shame. Correlation and hierarchical regression analyses were conducted to explore cross-sectional associations between variables. Results: Increased sense of social safeness was strongly correlated with reduced ED symptoms. Social safeness explained unique variance in ED symptoms independent of received and perceived social support. Shame and ED symptoms were positively correlated, while shame and safeness were negatively correlated. Conclusions: This study presents evidence of an association between the experience of social safeness and ED symptoms. The impact of the emotional experience of social safeness appears independent of current social support, and may be associated with increased activation of the soothing system, and reduced activation of the threat system and experiences of shame, as in the tripartite model of EDs. Further research could explore these associations in clinical populations and explore whether reduced social safeness is a risk factor for the development / maintenance of EDs, or could be a useful target for ED interventions. Plain english summary: This study looked for a possible link between having a greater general experience of 'safeness' in social relationships, and reduced eating disorder symptoms, in a healthy young adult sample. Eighty young adult participants completed online questionnaire measures of eating disorder symptoms, social safeness, social support, and shame. Having a greater sense of 'social safeness' was strongly correlated with having lower eating disorder symptoms. This effect seemed to exist independently of the level of social support someone reported. Shame was positively correlated with ED symptoms and negatively correlated with social safeness. These findings are consistent with the 'tripartite model' of emotion: the emotional experience of social safeness may be linked with increased activation of the soothing system and reduced activation of shame. A link between reduced experience of 'social safeness' and eating disorder symptoms may have useful implications for understanding and intervening with eating disorders. [ABSTRACT FROM AUTHOR]

Background: The widespread use of insecticide-treated nets (ITNs) has significantly contributed to the reduction in malaria cases and deaths observed across Africa. Unfortunately, this control strategy is threatened by the rapid spread of pyrethroid resistance in malaria vectors. Dual-active-ingredient insecticidal nets are now available to mitigate the impact of pyrethroid resistance. To facilitate evidence-based decisions regarding product selection in specific use settings, data are needed on the efficacy of these different nets against local mosquito populations. Methods: Two experimental hut trials were performed in Za-Kpota, southern Benin in 2021 to evaluate the performance of Interceptor G2 (BASF), Royal Guard (Disease Control Technologies) and PermaNet 3.0 (Vestergaard Frandsen), all dual-active-ingredient bednets, in comparison to untreated or standard pyrethroid-treated bednets, against free-flying wild Anopheles gambiae mosquitoes. The performance of some of these next-generation nets was compared to the same type of nets that have been in use for up to 2 years. Mosquitoes collected in the huts were followed up after exposure to assess the sublethal effects of treatments on certain life-history traits. Results: The predominant species in the study site was Anopheles gambiae sensu stricto (An. gambiae s.s.). Both Anopheles coluzzii and An. gambiae s.s. were resistant to pyrethroids (deltamethrin susceptibility was restored by piperonyl butoxide pre-exposure). In the experimental hut trials, the highest blood-feeding inhibition (5.56%) was recorded for the Royal Guard net, relative to the standard PermaNet 2.0 net (44.44% inhibition). The highest 72-h mortality rate (90.11%) was recorded for the Interceptor G2 net compared to the PermaNet 2.0 net (56.04%). After exposure, the risk of death of An. gambiae sensu lato (An. gambiae s.l.) was 6.5-fold higher with the Interceptor G2 net and 4.4-fold higher with the PermaNet 3.0 net compared to the respective untreated net. Lower mosquito mortality was recorded with an aged Interceptor G2 net compared to a new Interceptor G2 net. Oviposition rates were lower in mosquitoes collected from huts containing ITNs compared to those of untreated controls. None of the mosquitoes collected from huts equipped with Royal Guard nets laid any eggs. Conclusions: The Royal Guard and Interceptor G2 nets showed a potential to significantly improve the control of malaria-transmitting vectors. However, the PermaNet 3.0 net remains effective in pyrethroid-resistant areas. [ABSTRACT FROM AUTHOR]

Hybrid genotypes can provide significant yield gains over conventional inbred varieties due to heterosis or hybrid vigor. However, hybrids can also display unintended negative attributes or phenotypes such as extreme pathogen susceptibility. The necrotrophic pathogen Pyrenophora teres f. maculata (Ptm) causes spot form net blotch, which has caused significant yield losses to barley worldwide. Here, we report on a non-transgressive hybrid susceptibility locus in barley identified between the three parental lines CI5791, Tifang and Golden Promise that are resistant to Ptm isolate 13IM.3. However, F2 progeny from CI5791 × Tifang and CI5791 × Golden Promise crosses exhibited extreme susceptibility. The susceptible phenotype segregated in a ratio of 1 resistant:1 susceptible representing a genetic segregation ratio of 1 parental (res):2 heterozygous (sus):1 parental (res) suggesting a single hybrid susceptibility locus. Genetic mapping using a total of 715 CI5791 × Tifang F2 individuals (1430 recombinant gametes) and 149 targeted SNPs delimited the hybrid susceptibility locus designated Susceptibility to Pyrenophora teres 2 (Spt2) to an ~ 198 kb region on chromosome 5H of the Morex V3 reference assembly. This single locus was independently mapped with 83 CI5791 × Golden Promise F2 individuals (166 recombinant gametes) and 180 genome wide SNPs that colocalized to the same Spt2 locus. The CI5791 genome was sequenced using PacBio Continuous Long Read technology and comparative analysis between CI5791 and the publicly available Golden Promise genome assembly determined that the delimited region contained a single high confidence Spt2 candidate gene predicted to encode a pentatricopeptide repeat-containing protein. [ABSTRACT FROM AUTHOR]

Background: Wild emmer wheat is a great candidate to revitalize domesticated wheat genetic diversity. Recent years have seen intensive investigation into the evolution and domestication of wild emmer wheat, including whole-genome DNA and transcriptome sequencing. However, the impact of intraspecific hybridization on the transcriptome of wild emmer wheat has been poorly studied. In this study, we assessed changes in methylation patterns and transcriptomic variations in two accessions of wild emmer wheat collected from two marginal populations, Mt. Hermon and Mt. Amasa, and in their stable F4 hybrid. Results: Methylation-Sensitive Amplified Polymorphism (MSAP) detected significant cytosine demethylation in F4 hybrids vs. parental lines, suggesting potential transcriptome variation. After a detailed analysis, we examined nine RNA-Seq samples, which included three biological replicates from the F4 hybrid and its parental lines. RNA-Seq databases contained approximately 200 million reads, with each library consisting of 15 to 25 million reads. There are a total of 62,490 well-annotated genes in these databases, with 6,602 genes showing differential expression between F4 hybrid and parental lines Mt. Hermon and Mt. Amasa. The differentially expressed genes were classified into four main categories based on their expression patterns. Gene ontology (GO) analysis revealed that differentially expressed genes are associated with DNA/RNA metabolism, photosynthesis, stress response, phosphorylation and developmental processes. Conclusion: This study highlights the significant transcriptomic changes resulting from intraspecific hybridization within natural plant populations, which might aid the nascent hybrid in adapting to various environmental conditions. [ABSTRACT FROM AUTHOR]

Cassava ( Manihot esculenta Crantz) is a starchy root crop grown in the tropics mainly by small-scale farmers even though agro-industrial processing is rapidly increasing. For this processing market improved varieties with high dry matter root content (DMC) is required. Potentially toxic cyanogenic glucosides are synthesized in the leaves and translocated to the roots. Selection for varieties with low cyanogenic glucoside potential (CNP) and high DMC is among the principal objectives in cassava breeding programs. However, these traits are highly influenced by the environmental conditions and the genetic control of these traits is not well understood. An S1 population derived from a cross between two bred cassava varieties (MCOL 1684 and Rayong 1) that differ in CNP and DMC was used to study the heritability and genetic basis of these traits. A broad-sense heritability of 0.43 and 0.42 was found for CNP and DMC, respectively. The moderate heritabilities for DMC and CNP indicate that the phenotypic variation of these traits is explained by a genetic component. We found two quantitative trait loci (QTL) on two different linkage groups controlling CNP and six QTL on four different linkage groups controlling DMC. One QTL for CNP and one QTL for DMC mapped near each other, suggesting pleiotrophy and/or linkage of QTL. The two QTL for CNP showed additive effects while the six QTL for DMC showed additive effect, dominance or overdominance. This study is a first step towards developing molecular marker tools for efficient breeding of CNP and DMC in cassava. [ABSTRACT FROM AUTHOR]

Background: The link between host MHC (major histocompatibility complex) genotype and malaria is largely based on correlative data with little or no experimental control of potential confounding factors. We used an experimental mouse model to test for main effects of MHChaplotypes, MHC heterozygosity, and MHC × parasite clone interactions. We experimentally infected MHC-congenic mice (F2 segregants, homo- and heterozygotes, males and females) with one of two clones of Plasmodium chabaudi and recorded disease progression. Results: We found that MHC haplotype and parasite clone each have a significant influence on the course of the disease, but there was no significant host genotype by parasite genotype interaction. We found no evidence for overdominance nor any other sort of heterozygote advantage or disadvantage. Conclusion: When tested under experimental conditions, variation in the MHC can significantly influence the course of malaria. However, MHC heterozygote advantage through overdominance or dominance of resistance cannot be assumed in the case of single-strain infections. Future studies might focus on the interaction between MHC heterozygosity and multiple-clone infections. [ABSTRACT FROM AUTHOR]

Deleterious mutations affect genetic variation at linked neutral loci. Neutral variation can be reduced due to background selection, but in small population and with tight linkage such variation may increase due to associative overdominance. Here I report the results of computer simulations of diploid genotypes in small populations, where I look at the effect of deleterious mutations and linkage on comparisons of intra- and interspecific variation. Each chromosome consisted of 2000 loci where deleterious and neutral mutations occurred. The ratio of nonsynonymous to synonymous substitution rates (Ka/Ks) either increases with tight linkage or is unaffected, depending on the strength of selection. The ratio of the numbers of segregating mutations to the number of fixed mutations decreases under the conditions leading to background selection but can increase at tight linkage. Numbers of segregating sites (Sn) are less affected than nucleotide site diversity (π),π reduces more than Sn at intermediate linkage, butπ increases more than Sn when linkage is tight. Similar effects as found for Sn andπ are observed for heterozygosity and variance in allele size of tandem repeat loci. [ABSTRACT FROM AUTHOR]

Background: The callipyge mutation is located within an imprinted gene cluster on ovine chromosome 18. The callipyge trait exhibits polar overdominant inheritance due to the fact that only heterozygotes inheriting a mutant paternal allele (paternal heterozygotes) have a phenotype of muscle hypertrophy, reduced fat and a more compact skeleton. The mutation is a single A to G transition in an intergenic region that results in the increased expression of several genes within the imprinted cluster without changing their parent-of-origin allele-specific expression. Results: There was a significant effect of genotype (p < 0.0001) on the transcript abundance of DLK1, PEG11, and MEG8 in the muscles of lambs with the callipyge allele. DLK1 and PEG11 transcript levels were elevated in the hypertrophied muscles of paternal heterozygous animals relative to animals of the other three genotypes. The PEG11 locus produces a single 6.5 kb transcript and two smaller antisense strand transcripts, referred to as PEG11AS, in skeletal muscle. PEG11AS transcripts were detectable over a 5.5 kb region beginning 1.2 kb upstream of the PEG11 start codon and spanning the entire open reading frame. Analysis of PEG11 expression by quantitative PCR shows a 200-fold induction in the hypertrophied muscles of paternal heterozygous animals and a 13-fold induction in homozygous callipyge animals. PEG11 transcripts were 14-fold more abundant than PEG11AS transcripts in the gluteus medius of paternal heterozygous animals. PEG11AS transcripts were expressed at higher levels than PEG11 transcripts in the gluteus medius of animals of the other three genotypes. Conclusions: The effect of the callipyge mutation has been to alter the expression of DLK1, GTL2, PEG11 and MEG8 in the hypertrophied skeletal muscles. Transcript abundance of DLK1 and PEG11 was highest in paternal heterozygous animals and exhibited polar overdominant gene expression patterns; therefore, both genes are candidates for causing skeletal muscle hypertrophy. There was unique relationship of PEG11 and PEG11AS transcript abundance in the paternal heterozygous animals that suggests a RNA interference mechanism may have a role in PEG11 gene regulation and polar overdominance in callipyge sheep. [ABSTRACT FROM AUTHOR]

Background: Heterosis has successfully enhanced maize productivity and quality. Although significant progress has been made in delineating the genetic basis of heterosis, the molecular mechanisms underlying its genetic components remain less explored. Allele-specific expression (ASE), the imbalanced expression between two parental alleles in hybrids, is increasingly being recognized as a factor contributing to heterosis. ASE is a complex process regulated by both epigenetic and genetic variations in response to developmental and environmental conditions. Results: In this study, we explored the differential characteristics of ASE by analyzing the transcriptome data of two maize hybrids and their parents under four light conditions. On the basis of allele expression patterns in different hybrids under various conditions, ASE genes were divided into three categories: bias-consistent genes involved in basal metabolic processes in a functionally complementary manner, bias-reversal genes adapting to the light environment, and bias-specific genes maintaining cell homeostasis. We observed that 758 ASE genes (ASEGs) were significantly overlapped with heterosis quantitative trait loci (QTLs), and high-frequency variations in the promoter regions of heterosis-related ASEGs were identified between parents. In addition, 10 heterosis-related ASEGs participating in yield heterosis were selected during domestication. Conclusions: The comprehensive analysis of ASEGs offers a distinctive perspective on how light quality influences gene expression patterns and gene-environment interactions, with implications for the identification of heterosis-related ASEGs to enhance maize yield. [ABSTRACT FROM AUTHOR]

Background: Evolutionary processes leave footprints along the genome over time. Highly homozygous regions may correspond to positive selection of favorable alleles, while maintenance of heterozygous regions may be due to balancing selection phenomena. We analyzed data from 176 fish from four disconnected domestic rainbow trout populations that were genotyped using a high-density Axiom Trout genotyping 665K single nucleotide polymorphism array, including 20 from the US and 156 from three French lines. Using methods based on runs of homozygosity and extended haplotype homozygosity, we detected signatures of selection in these four populations. Results: Nine genomic regions that included 253 genes were identified as being under positive selection in all four populations Most were located on chromosome 2 but also on chromosomes 12, 15, 16, and 20. In addition, four heterozygous regions that contain 29 genes that are putatively under balancing selection were also shared by the four populations. These were located on chromosomes 10, 13, and 19. Regardless of the homozygous or heterozygous nature of the regions, in each region, we detected several genes that are highly conserved among vertebrates due to their critical roles in cellular and nuclear organization, embryonic development, or immunity. We identified new candidate genes involved in rainbow trout fitness, as well as 17 genes that were previously identified to be under positive selection, 10 of which in other fishes (auts2, atp1b3, zp4, znf135, igf-1α, brd2, col9a2, mrap2, pbx1, and emilin-3). Conclusions: Using material from disconnected populations of different origins allowed us to draw a genome-wide map of signatures of positive selection that are shared between these rainbow trout populations, and to identify several regions that are putatively under balancing selection. These results provide a valuable resource for future investigations of the dynamics of genetic diversity and genome evolution during domestication. [ABSTRACT FROM AUTHOR]

Introduction: The Ovar-DRB1 gene, a crucial element of the Major Histocompatibility Complex (MHC) Class II region, initiates adaptive immunity by presenting antigens to T-cells. Genetic diversity in sheep, particularly in MHC Class II genes like Ovar-DRB1, directly influences the specturm of presented antigens impacting immune responses and disease susceptability. Understanding the allelic diversity of Ovar-DRB1 gene in Sudan Desert Sheep (SDS) is essential for uncovering the genetic basis of immune responses and disease resistance, given the the breeds significance in Sudan's unique environment. Methods: Utilizing Targeted Next-Generation Sequencing (NGS) we explore allelic diversity in Ovar-DRB1 gene within SDS. Successfully ampliying and and sequencing the second exon of this gene in 288 SDS samples representing six breeds provided a comprehensive allelic profile, enabling a detalied examination of the gene's genetic makeup. Results: We identifed forty-six alleles, including four previously unreported, enrichness the genetic diversity of SDS breeds. These alleles exhibiting non-uniform distribution, varying frequencies across breeds, indicating a breed-specific genetic landscape. Certain alleles, known and novel, show higher frequencies in specific populations, suggesting potential associations with adaptive immune responses. Identifying these alleles sets the stage for investigating their functional roles and implications for disease resistance. Genetic differentiation among SDS breeds, as indicated by FST values and clustering analyses, highlights a unique genetic makeup shaped by geographic and historical factors. These differentiation patterns among SDS breeds have broader implications for breed conservation and targeted breeding to enhance disease resistance in specific populations. Conclusion: This study unveils Ovar-DRB1 gene allelic diversity in SDS breeds through targeted NGS and genetic analyses, revealing new alleles that underscore the breeds' unique genetic profile. Insights into the genetic factors governing immune responses and disease resistance emerge, promising for optimization of breeding strategies for enhanced livestock health in Sudan's unique environment. [ABSTRACT FROM AUTHOR]

Background: Genomic heterozygosity has been shown to confer a health advantage in humans and play a protective role in complex diseases. Given osteoarthritis (OA) is a highly polygenic disease, we set out to determine if an association exists between OA and genomic heterozygosity. Results: End-stage knee and hip OA patients and healthy controls were recruited from the Newfoundland and Labrador (NL) population. The Arthritis Research UK Osteoarthritis Genetics (arcOGEN) consortium database was utilized as a replication cohort. DNA was extracted from blood samples and genotyped. Individual rates of observed heterozygosity (HetRate) and heterozygosity excess (HetExcess) relative to the expected were mathematically derived, and standardized to a z-score. Logistic regression modeling was used to examine the association between OA and HetRate or HetExcess. A total of 559 knee and hip OA patients (mean age 66.5 years, body mass index (BMI) 33.7 kg/m2, and 55% females) and 118 healthy controls (mean age 56.4 years, BMI 29.5 kg/m2, and 59% female) were included in the NL cohort analysis. We found that OA had an inverse relationship with HetRate and HetExcess with odds ratios of 0.64 (95% CI: 0.45–0.91) and 0.65 (95% CI: 0.45–0.93) per standard deviation (SD), respectively. The arcOGEN data included 2,019 end-stage knee and hip OA patients and 2,029 healthy controls, validating our findings with HetRate and HetExcess odds ratios of 0.60 (95% CI: 0.56–0.64) and 0.44 (95% CI: 0.40–0.47) per SD, respectively. Conclusions: Our results are the first to clearly show evidence, from two separate cohorts, that reduced genomic heterozygosity confers a risk for the future development of OA. [ABSTRACT FROM AUTHOR]

Background: The association between TCF7L2 and CAPN10 gene polymorphisms and gestational diabetes mellitus (GDM) has been explored in diverse populations across different geographical regions. Yet, most of these studies have been confined to a limited number of loci, resulting in inconsistent findings. In this study, we conducted a comprehensive review of published literature to identify studies examining the relationship between TCF7L2 and CAPN10 gene polymorphisms and the incidence of GDM in various populations. We specifically focused on five loci that were extensively reported in a large number of publications and performed a meta-analysis. Methods: We prioritized the selection of SNPs with well-documented correlations established in existing literature on GDM. We searched eight Chinese and English databases: Cochrane, Elton B. Stephens. Company (EBSCO), Embase, Scopus, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal Database and retrieved all relevant articles published between the inception of the database and July 2022. The Newcastle Ottawa Scale (NOS) was used to evaluate the selected articles, and the odds ratio (OR) was used as the combined effect size index to determine the association between genotypes, alleles, and GDM using different genetic models. Heterogeneity between the studies was quantified and the I2 value calculated. Due to large heterogeneities between different ethnic groups, subgroup analysis was used to explore the correlation between genetic polymorphisms and the incidence of GDM in the different populations. The stability of the results was assessed using sensitivity analysis. Begg's and Egger's tests were used to assess publication bias. Results: A total of 39 articles reporting data on 8,795 cases and 16,290 controls were included in the analysis. The frequency of the rs7901695 genotype was statistically significant between cases and controls in the European population (OR = 0.72, 95% CI: 0.65–0.86) and the American population (OR = 0.61, 95% CI: 0.48–0.77). The frequencies of rs12255372, rs7901695, rs290487, and rs2975760 alleles were also considerably different between the cases and controls in the populations analyzed. Conclusions: rs7903146, rs12255372, rs7901695, rs290487, and rs2975760 were associated with the incidence of GDM in different populations. [ABSTRACT FROM AUTHOR]

Background: Plant domestication is a remarkable example of rapid phenotypic transformation of polygenic traits, such as organ size. Evidence from a handful of study cases suggests this transformation is due to gene regulatory changes that result in non-additive phenotypes. Employing data from published genetic crosses, we estimated the role of non-additive gene action in the modulation of transcriptional landscapes in three domesticated plants: maize, sunflower, and chili pepper. Using A. thaliana, we assessed the correlation between gene regulatory network (GRN) connectivity properties, transcript abundance variation, and gene action. Finally, we investigated the propagation of non-additive gene action in GRNs. Results: We compared crosses between domesticated plants and their wild relatives to a set of control crosses that included a pair of subspecies evolving under natural selection and a set of inbred lines evolving under domestication. We found abundance differences on a higher portion of transcripts in crosses between domesticated-wild plants relative to the control crosses. These transcripts showed non-additive gene action more often in crosses of domesticated-wild plants than in our control crosses. This pattern was strong for genes associated with cell cycle and cell fate determination, which control organ size. We found weak but significant negative correlations between the number of targets of trans-acting genes (Out-degree) and both the magnitude of transcript abundance difference a well as the absolute degree of dominance. Likewise, we found that the number of regulators that control a gene's expression (In-degree) is weakly but negatively correlated with the magnitude of transcript abundance differences. We observed that dominant-recessive gene action is highly propagable through GRNs. Finally, we found that transgressive gene action is driven by trans-acting regulators showing additive gene action. Conclusions: Our study highlights the role of non-additive gene action on modulating domestication-related traits, such as organ size via regulatory divergence. We propose that GRNs are shaped by regulatory changes at genes with modest connectivity, which reduces the effects of antagonistic pleiotropy. Finally, we provide empirical evidence of the propagation of non-additive gene action in GRNs, which suggests a transcriptional epistatic model for the control of polygenic traits, such as organ size. [ABSTRACT FROM AUTHOR]

Background: Polar overdominance at the ovine callipyge (CLPG) locus involves the post-transcriptional trans-inhibition of DLK1 in skeletal muscle of CLPG/CLPG sheep. The abundant maternally expressed microRNAs (miRNAs) mapping to the imprinted DLK1-GTL2 domain are prime candidate mediators of this trans-effect. Results: We have tested the affinity of 121 miRNAs processed from this locus for DLK1 by co-transfecting COS1 cells with a vector expressing the full-length ovine DLK1 with corresponding mimic miRNAs. None of the tested miRNAs was able to down regulate DLK1 to the extent observed in vivo. Conclusions: This suggests that other factors, with or without these miRNAs, are involved in mediating the observed trans-effect. [ABSTRACT FROM AUTHOR]

Background Chalkiness is a major constraint in rice production because it is one of the key factors determining grain quality (appearance, processing, milling, storing, eating, and cooking quality) and price. Its reduction is a major goal, and the primary purpose of this study was to dissect the genetic basis of grain chalkiness. Using five populations across two environments, we also sought to determine how many quantitative trait loci (QTL) can be consistently detected. We obtained an integrated genetic map using the data from five mapping populations and further confirmed the reliability of the identified QTL. Results A total of 79 QTL associated with six chalkiness traits (chalkiness rate, white core rate, white belly rate, chalkiness area, white core area, and white belly area) were mapped on 12 chromosomes using five populations (two doubled haploid lines and three recombinant inbred lines) across two environments (Hainan in 2004 and Wuhan in 2004). The final integrated map included 430 markers; 58.3% of the QTL clustered together (QTL clusters), 71.4% of the QTL clusters were identified in two or more populations, and 36.1% of the QTL were consistently detected in the two environments. The QTL could be detected again and showed dominance (qWBR1, qWBR8, qWBR12, and qCR5) or overdominance effects (qWCR7) for the rate of the white belly or white core, respectively, and all four QTL clusters derived from Zhenshan 97 controlling white belly rate were stably and reliably identified in an F2 population. Conclusions Our results identified 79 QTL associated with six chalkiness traits using five populations across two environments and yielded an integrated genetic map, indicating most of the QTL clustered together and could be detected in different backgrounds. The identified QTL were stable and reliable in the F2 population, and they may facilitate our understanding of the QTL related to chalkiness traits in different populations and various environments, the relationships among the various chalkiness QTL, and the genetic basis for chalkiness. Thus, our results may be immediately used for map-based cloning of important QTL and in marker-assisted breeding to improve grain quality in rice breeding. [ABSTRACT FROM AUTHOR]

Background: Snake venom is shaped by the ecology and evolution of venomous species, and signals of positive selection in toxins have been consistently documented, reflecting the role of venoms as an ecologically critical phenotype. New World coral snakes (Elapidae) are represented by three genera and over 120 species and subspecies that are capable of causing significant human morbidity and mortality, yet coral-snake venom composition is poorly understood in comparison to that of Old World elapids. High-throughput sequencing is capable of identifying thousands of loci, while providing characterizations of expression patterns and the molecular evolutionary forces acting within the venom gland. Results: We describe the de novo assembly and analysis of the venom-gland transcriptome of the eastern coral snake (Micrurus fulvius). We identified 1,950 nontoxin transcripts and 116 toxin transcripts. These transcripts accounted for 57.1% of the total reads, with toxins accounting for 45.8% of the total reads. Phospholipases A2 and three-finger toxins dominated expression, accounting for 86.0% of the toxin reads. A total of 15 toxin families were identified, revealing venom complexity previously unknown from New World coral snakes. Toxins exhibited high levels of heterozygosity relative to nontoxins, and overdominance may favor gene duplication leading to the fixation of advantageous alleles. Phospholipase A2 expression was uniformly distributed throughout the class while three-finger toxin expression was dominated by a handful of transcripts, and phylogenetic analyses indicate that toxin divergence may have occurred following speciation. Positive selection was detected in three of the four most diverse toxin classes, suggesting that venom diversification is driven by recurrent directional selection. Conclusions: We describe the most complete characterization of an elapid venom gland to date. Toxin gene duplication may be driven by heterozygote advantage, as the frequency of polymorphic toxin loci was significantly higher than that of nontoxins. Diversification among toxins appeared to follow speciation reflecting species-specific adaptation, and this divergence may be directly related to dietary shifts and is suggestive of a coevolutionary arms race. [ABSTRACT FROM AUTHOR]

Background: Utilization of heterosis in maize could be critical in maize breeding for boosting grain yield. However, the genetic architecture of heterosis is not fully understood. To dissect the genetic basis of yield-related traits and heterosis in maize, 301 recombinant inbred lines derived from 08 to 641 × YE478 and 298 hybrids from the immortalized F2 (IF2) population were used to map quantitative trait loci (QTLs) for nine yield-related traits and mid-parent heterosis. Results: We observed 156 QTLs, 28 pairs of loci with epistatic interaction, and 10 significant QTL × environment interactions in the inbred and hybrid mapping populations. The high heterosis in F1 and IF2 populations for kernel weight per ear (KWPE), ear weight per ear (EWPE), and kernel number per row (KNPR) matched the high percentages of QTLs (over 50%) for those traits exhibiting overdominance, whereas a notable predominance of loci with dominance effects (more than 70%) was observed for traits that show low heterosis such as cob weight per ear (CWPE), rate of kernel production (RKP), ear length (EL), ear diameter (ED), cob diameter, and row number (RN). The environmentally stable QTL qRKP3–2 was identified across two mapping populations, while qKWPE9, affecting the trait mean and the mid-parent heterosis (MPH) level, explained over 18% of phenotypic variations. Nine QTLs, qEWPE9–1, qEWPE10–1, qCWPE6, qEL8, qED2–2, qRN10–1, qKWPE9, qKWPE10–1, and qRKP4–3, accounted for over 10% of phenotypic variation. In addition, QTL mapping identified 95 QTLs that were gathered together and integrated into 33 QTL clusters on 10 chromosomes. Conclusions: The results revealed that (1) the inheritance of yield-related traits and MPH in the heterotic pattern improved Reid (PA) × Tem-tropic I (PB) is trait-dependent; (2) a large proportion of loci showed dominance effects, whereas overdominance also contributed to MPH for KNPR, EWPE, and KWPE; (3) marker-assisted selection for markers at genomic regions 1.09–1.11, 2.04, 3.08–3.09, and 10.04–10.05 contributed to hybrid performance per se and heterosis and were repeatedly reported in previous studies using different heterotic patterns is recommended. [ABSTRACT FROM AUTHOR]

Background: Insecticides are an effective and practical tool for reducing malaria transmission but the development of resistance to the insecticides can potentially compromise controls efforts. In this study a mathematical model was developed to explore the effects on mosquito populations of spatial heterogeneous deployment of insecticides. This model was used to identify important parameters in the evolution of insecticide resistance and to examine the contribution of new generation long-lasting insecticidal bed nets, that incorporate a chemical synergist on the roof panel, in delaying insecticide resistance. Methods: A genetic model was developed to predict changes in mosquito fitness and resistance allele frequency. Parameters describing insecticide selection, fitness cost and the additional use of synergist were incorporated. Uncertainty and sensitivity analysis were performed followed by investigation of the evolution of resistance under scenarios of fully effective or ineffective synergists. Results: The spread of resistance was most sensitive to selection coefficients, fitness cost and dominance coefficients while mean fitness was most affected by baseline fitness levels. Using a synergist delayed the spread of resistance but could, in specific circumstances that were thoroughly investigated, actually increase the rate of spread. Different spread dynamics were observed, with simulations leading to fixation, loss and most interestingly, equilibrium (without explicit overdominance) of the resistance allele. Conclusions: This strategy has the potential to delay the spread of resistance but note that in an heterogeneous environment it can also lead to the opposite effect, i.e., increasing the rate of spread. This clearly emphasizes that selection pressure acting inside the house cannot be treated in isolation but must be placed in context of overall insecticide use in an heterogeneous environment. [ABSTRACT FROM AUTHOR]

Background: The inability to reduce or regulate alcohol intake is a hallmark symptom for alcohol use disorders. Research on novel behavioral and genetic models of experience-induced changes in drinking will further our knowledge on alcohol use disorders. Distinct alcohol self-administration behaviors were previously observed when comparing two F1 hybrid strains of mice: C57BL/6J x NZB/B1NJ (BxN) show reduced alcohol preference after experience with high concentrations of alcohol and periods of abstinence while C57BL/6J x FVB/NJ (BxF) show sustained alcohol preference. These phenotypes are interesting because these hybrids demonstrate the occurrence of genetic additivity (BxN) and overdominance (BxF) in ethanol intake in an experience dependent manner. Specifically, BxF exhibit sustained alcohol preference and BxN exhibit reduced alcohol preference after experience with high ethanol concentrations; however, experience with low ethanol concentrations produce sustained alcohol preference for both hybrids. In the present study, we tested the hypothesis that these phenotypes are represented by differential production of the inducible transcription factor, ΔFosB, in reward, aversion, and stress related brain regions. Results: Changes in neuronal plasticity (as measured by Δlevels) were experience dependent, as well as brain region and genotype specific, further supporting that neuronal circuitry underlies motivational aspects of ethanol consumption. BxN mice exhibiting reduced alcohol preference had lower ΔFosB levels in the Edinger-Westphal nucleus than mice exhibiting sustained alcohol preference, and increased ΔFosB levels in central medial amygdala as compared with control mice. BxN mice showing sustained alcohol preference exhibited higher ΔFosB levels in the ventral tegmental area, Edinger-Westphal nucleus, and amygdala (central and lateral divisions). Moreover, in BxN mice ΔFosB levels in the Edinger-Westphal nucleus and ventral tegmental regions significantly positively correlated with ethanol preference and intake. Additionally, hierarchical clustering analysis revealed that many ethanol-naïve mice with overall low ΔFosB levels are in a cluster, whereas many mice displaying sustained alcohol preference with overall high ΔFosB levels are in a cluster together. Conclusions: By comparing and contrasting two alcohol phenotypes, this study demonstrates that the reward- and stress-related circuits (including the Edinger-Westphal nucleus, ventral tegmental area, amygdala) undergo significant plasticity that manifests as reduced alcohol preference. [ABSTRACT FROM AUTHOR]

Background: The extreme polymorphism that is observed in major histocompatibility complex (MHC) genes, which code for proteins involved in recognition of non-self oligopeptides, is thought to result from a pressure exerted by parasites because parasite antigens are more likely to be recognized by MHC heterozygotes (heterozygote advantage) and/or by rare MHC alleles (negative frequency-dependent selection). The Ewens- Watterson test (EW) is often used to detect selection acting on MHC genes over the recent history of a population. EW is based on the expectation that allele frequencies under balancing selection should be more even than under neutrality. We used computer simulations to investigate whether this expectation holds for selection exerted by parasites on host MHC genes under conditions of heterozygote advantage and negative frequency-dependent selection acting either simultaneously or separately. Results: In agreement with simple models of symmetrical overdominance, we found that heterozygote advantage acting alone in populations does, indeed, result in more even allele frequency distributions than expected under neutrality, and this is easily detectable by EW. However, under negative frequency-dependent selection, or under the joint action of negative frequency-dependent selection and heterozygote advantage, distributions of allele frequencies were less predictable: the majority of distributions were indistinguishable from neutral expectations, while the remaining runs resulted in either more even or more skewed distributions than under neutrality. Conclusions: Our results indicate that, as long as negative frequency-dependent selection is an important force maintaining MHC variation, the EW test has limited utility in detecting selection acting on these genes. [ABSTRACT FROM AUTHOR]

Background: The observed correlation between ultraviolet light incidence and skin color, together with the geographical apportionment of skin reflectance among human populations, suggests an adaptive value for the pigmentation of the human skin. We have used Affymetrix U133a v2.0 gene expression microarrays to investigate the expression profiles of a total of 9 melanocyte cell lines (5 from lightly pigmented donors and 4 from darkly pigmented donors) plus their respective unirradiated controls. In order to reveal signatures of selection in loci with a bearing on skin pigmentation in humans, we have resequenced between 4 to 5 kb of the proximal regulatory regions of three of the most differently expressed genes, in the expectation that variation at regulatory regions might account for intraespecific morphological diversity, as suggested elsewhere. Results: Contrary to our expectations, expression profiles did not cluster the cells into unirradiated versus irradiated melanocytes, or into lightly pigmented versus darkly pigmented melanocytes. Instead, expression profiles correlated with the presence of Bovine Pituitary Extract (known to contain α-MSH) in the media. This allowed us to differentiate between melanocytes that are synthesizing melanin and those that are not. TYR, TYRP1 and DCT were among the five most differently expressed genes between these two groups. Population genetic analyses of sequence haplotypes of the proximal regulatory flanking-regions included Tajima's D, HEW and DHEW neutrality tests analysis. These were complemented with EHH tests (among others) in which the significance was obtained by a novel approach using extensive simulations under the coalescent model with recombination. We observe strong evidence for positive selection for TYRP1 alleles in Africans and for DCT and TYRP1 in Asians. However, the overall picture reflects a complex pattern of selection, which might include overdominance for DCT in Europeans. Conclusion: Diversity patterns clearly evidence adaptive selection in pigmentation genes in Africans and Asians. In Europeans, the evidence is more complex, and both directional and balancing selection may be involved in light skin. As a result, different non-African populations may have acquired light skin by alternative ways, and so light skin, and perhaps dark skin too, may be the result of convergent evolution. [ABSTRACT FROM AUTHOR]

A previous genetic map containing 117 microsatellite loci and 400 F2 plants was used for quantitative trait loci (QTL) mapping in tropical maize. QTL were characterized in a population of 400 F2:3 lines, derived from selfing the F2 plants, and were evaluated with two replications in five environments. QTL determinations were made from the mean of these five environments. Grain yield (GY), plant height (PH), ear height (EH) and grain moisture (GM) were measured. Variance components for genotypes (G), environments (E) and G×E interaction were highly significant for all traits. Heritability was 0.69 for GY, 0.66 for PH, 0.67 for EH and 0.23 for GM. Using composite interval mapping (CIM), a total of 13 distinct QTLs were identified: four for GY, four for PH and five for EH. No QTL was detected for GM. The QTL explained 32.73 % of the phenotypic variance of GY, 24.76 % of PH and 20.91 % of EH. The 13 QTLs displayed mostly partial dominance or overdominance gene action and mapped to chromosomes 1, 2, 7, 8 and 9. Most QTL alleles conferring high values for the traits came from line L-14-4B. Mapping analysis identified genomic regions associated with two or more traits in a manner that was consistent with correlation among traits, supporting either pleiotropy or tight linkage among QTL. The low number of QTLs found, can be due to the great variation that exists among tropical environments. [ABSTRACT FROM AUTHOR]