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Death-feigning behavior is an anti-predator behavior in a wide range of animal taxa, and it often correlates with the movement (i.e. death-feigning syndrome). In the present study, we performed reciprocal crossing among strains with genetically longer (L strain) and shorter (S strain) duration of death feigning, and investigated related heritable factors in the F1 and F2 populations. We also investigated moving activity which negatively responded to artificial selection for death feigning in T. castaneum. Our results showed that death feigning occurred more frequently and for shorter periods in the F1 population. In the F2 population, death feigning and movement showed continuous segregation. The distribution of each trait value in the F2 generation was different from the distribution of trait values in the parental generation, and no individuals transgressing the distribution of trait values in the parental generation emerged in the F2 generation. Chi-square analysis of the observed death feigning and movement of F1 and F2 progenies rejected the hypothesis of mono-major gene inheritance. These results suggest that death-feigning syndrome is controlled in a polygenic manner. Our study indicated that reciprocal crossing experiments are useful in assessing the quantitative inheritance of behavioral traits.

Evolutionary computation has largely exhibited its potential to complement conventional learning algorithms in a variety of Machine Learning tasks, especially those related to unsupervised (clustering) and supervised learning. It has not been until lately when the computational efficiency of evolutionary solvers has been put in prospective for training reinforcement learning models. However, most studies framed so far within this context have considered environments and tasks conceived in isolation, without any exchange of knowledge among related tasks. In this manuscript we present A-MFEA-RL, an adaptive version of the well-known MFEA algorithm whose search and inheritance operators are tailored for multitask reinforcement learning environments. Specifically, our approach includes crossover and inheritance mechanisms for refining the exchange of genetic material, which rely on the multi-layered structure of modern Deep Learning based reinforcement learning models. In order to assess the performance of the proposed approach, we design an extensive experimental setup comprising multiple reinforcement learning environments of varying levels of complexity, over which the performance of A-MFEA-RL is compared to that furnished by alternative non-evolutionary multitask reinforcement learning approaches. As concluded from the discussion of the obtained results, A-MFEA-RL not only achieves competitive success rates over the simultaneously addressed tasks, but also fosters the exchange of knowledge among tasks that could be intuitively expected to keep a degree of synergistic relationship.

Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA, because of its nonchromosomal inheritance, drives high-copy-number oncogene amplification and enables tumors to evolve their genomes rapidly. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription, and the higher-order organization of ecDNA contributes to tumor pathogenesis. Consequently, patients whose cancers harbor ecDNA have significantly shorter survival. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. In this review, we discuss the current state of understanding of how ecDNAs form and function as well as how they contribute to drug resistance and accelerated cancer evolution. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Summary Identifying whether a given genetic mutation results in a gene product with increased (gain-of-function; GOF) or diminished (loss-of-function; LOF) activity is an important step toward understanding disease mechanisms because they may result in markedly different clinical phenotypes. Here, we generated an extensive database of documented germline GOF and LOF pathogenic variants by employing natural language processing (NLP) on the available abstracts in the Human Gene Mutation Database. We then investigated various gene- and protein-level features of GOF and LOF variants and applied machine learning and statistical analyses to identify discriminative features. We found that GOF variants were enriched in essential genes, for autosomal-dominant inheritance, and in protein binding and interaction domains, whereas LOF variants were enriched in singleton genes, for protein-truncating variants, and in protein core regions. We developed a user-friendly web-based interface that enables the extraction of selected subsets from the GOF/LOF database by a broad set of annotated features and downloading of up-to-date versions. These results improve our understanding of how variants affect gene/protein function and may ultimately guide future treatment options.

Repeats are prevalent in the genomes of all bacteria, plants and animals, and they cover nearly half of the Human genome, which play indispensable roles in the evolution, inheritance, variation and genomic instability, and serve as substrates for chromosomal rearrangements that include disease-causing deletions, inversions, and translocations. Comprehensive identification, classification and annotation of repeats in genomes can provide accurate and targeted solutions towards understanding and diagnosis of complex diseases, optimization of plant properties and development of new drugs. RepBase and Dfam are two most frequently used repeat databases, but they are not sufficiently complete. Due to the lack of a comprehensive repeat database of multiple species, the current research in this field is far from being satisfactory. LongRepMarker is a new framework developed recently by our group for comprehensive identification of genomic repeats. We here propose msRepDB based on LongRepMarker, which is currently the most comprehensive multi-species repeat database, covering >80 000 species. Comprehensive evaluations show that msRepDB contains more species, and more complete repeats and families than RepBase and Dfam databases. (https://msrepdb.cbrc.kaust.edu.sa/pages/msRepDB/index.html).

One of the most important goals of the post-genomic era is to understand the different sources of molecular information that regulate the functional and structural architecture of cells. In this regard, Prof. K. Baverstock underscores in his recent article “The gene: An appraisal” (Baverstock, 2021) that genes are not the leading elements in cellular functionality, inheritance and evolution. As a consequence, the theory of evolution based on the Neo-Darwinian synthesis, is inadequate for today's scientific evidence. Conversely, the author contends that life processes viewed on the basis of thermodynamics, complex system dynamics and self-organization provide a new framework for the foundations of Biology. I consider it necessary to comment on some essential aspects of this relevant work, and here I present a short overview of the main non-genetic sources of biomolecular order and complexity that underline the molecular dynamics and functionality of cells. These sources generate different processes of complexity, which encompasses from the most elementary levels of molecular activity to the emergence of systemic behaviors, and the information necessary to sustain them is not contained in the genome.

In this article I argue that we should pay extra attention to the ecological dimension of natural selection. By this I mean that we should view natural selection primarily as acting on the outcomes of the interactions organisms have with their environment, which influences their relative reproductive output. A consequence of this view is that natural selection is not (directly) sensitive to what system of inheritance ensures reoccurrences of organism-environment interactions over generations. I end by showing the consequences of this view when looking at how processes like niche construction and the Baldwin effect relate to natural selection.

Wheat is a staple food for a large part of the world's population and faces a continuous demand for increased productivity. The presence of genetic variability allows the success in developing cultivars with higher yield. The understanding of the genetic variability available is crucial for their effective use in breeding programs. Inheritance of wheat yield components is complex, due to polygenic control and the strong influence of the environment. Therefore, an accurate heritability estimation can accelerate the selection gains towards increasing wheat yield. Thus, this study aimed to characterize agronomic traits related to yield in a collection of 99 wheat accessions used in Brazil. In addition, the heritability of these traits was estimated. The studied accessions showed variability for yield, which can be explained by the presence of variability in most yield components. Cluster analysis showed that there is variability in wheat genotypes, however, the introduction of new sources of variability in crossing blocks or the induction of mutations is suggested. The broad-sense heritability for grain yield was considered high, as well as for most of the studied agronomic traits, suggesting that it is possible to obtain genetic gain with selection in this environment. However, for greater accuracy, genetic gain values should be estimated and considered when designing selection strategies. Hectoliter weight showed low heritability, demonstrating the complexity of selection for this trait. In summary, this study demonstrates the presence of genetic variability and high heritability for agronomic traits, enabling genetic gain in breeding programs using these wheat accessions.

Emmer wheat (Triticum turgidum ssp. dicoccum) is an important gene source for wheat improvement but less studied in crosses with its descendant species durum (Triticum turgidum ssp. durum), especially in respect to the type of genetic components, intergenic interactions and the genetic mechanisms governing responses to drought. In this study, generation means analysis was performed using F1, F2, BC1P1 and BC1P2 from two different crosses of emmer × durum. Seeds were planted in a RCBD design with three replications under two water regimes. Results showed that there was a highly considerable difference between generations for all studied traits. The presence of significant mean parameter for all the traits, indicated the quantitative inheritance of the traits. Estimating the number of effective genes, polygenic control of the traits were confirmed. In moisture stress condition, epistatic effect for grain yield and yield-related traits illustrated the importance of epistasis in plant adaptation and performance stability. The additive × additive effect, which is fixable, was remarkable in both crosses. Under both water regimes, narrow-sense heritability was relatively high and estimates of gain from selection were positive for most of the traits. Among generations studied, the backcrosses were superior for drought tolerant indices. Based on the results, emmer wheat seems to have genetic potential for durum improvement.

Background Over the last few decades, we increasingly see examples of parental environmental experiences influencing offspring health and fitness. More recently, it has become clear that some non-genetic effects can be conferred across multiple generations. This topic has attracted research from a diversity of disciplines such as toxicology, biomedical sciences, and ecology, due to its importance for environmental and health issues, as well as ecological and evolutionary processes, with implications for environmental policies. The rapid accumulation of primary research has enabled researchers to perform systematic reviews (SRs), including meta-analyses, to investigate the generality of and sources of variation in non-genetic effects. However, different disciplines ask different questions and SRs can vary substantially in scope, quality, and terminology usage. This diversity in SRs makes it difficult to assess broad patterns of non-genetic effects across disciplines as well as determine common areas of interest and gaps in the literature. To clarify research patterns within the SR literature on non-genetic inheritance, we plan to create a map of systematic reviews as well as conduct bibliometric mapping (referred to as ‘research weaving’). We will address four key questions: first, what are the broad research patterns unifying the SR literature on non-genetic inheritance across disciplines? Second, are there discipline-specific research patterns, including terminology use, between disciplines? Third, how are authors of the SR literature connected? Fourth, what is the reliability of the SR literature? Methods We will systematically collect reviews within the SR ‘family’ that examine non-genetic inheritance arising from parental and ancestral environment by searching databases for journal articles and grey literature, as well as conducting backwards and forwards searching. Search hits will be double screened using ‘decision trees’ that represent the inclusion criteria. All relevant data elements on the review’s topic, as well as a critical appraisal of the review’s approach and reporting, will be extracted into Excel flat sheets. Bibliometric data will be directly extracted from Scopus. We will then query all relevant data elements to address our objectives and present outcomes in easily interpretable tables and figures, accompanied by a narrative description of results.

Background Deep learning is an active bioinformatics artificial intelligence field that is useful in solving many biological problems, including predicting altered epigenetics such as DNA methylation regions. Deep learning (DL) can learn an informative representation that addresses the need for defining relevant features. However, deep learning models are computationally expensive, and they require large training datasets to achieve good classification performance. Results One approach to addressing these challenges is to use a less complex deep learning network for feature selection and Machine Learning (ML) for classification. In the current study, we introduce a hybrid DL-ML approach that uses a deep neural network for extracting molecular features and a non-DL classifier to predict environmentally responsive transgenerational differential DNA methylated regions (DMRs), termed epimutations, based on the extracted DL-based features. Various environmental toxicant induced epigenetic transgenerational inheritance sperm epimutations were used to train the model on the rat genome DNA sequence and use the model to predict transgenerational DMRs (epimutations) across the entire genome. Conclusion The approach was also used to predict potential DMRs in the human genome. Experimental results show that the hybrid DL-ML approach outperforms deep learning and traditional machine learning methods.

Inborn errors of immunity (IEIs) include several hundred gene defects affecting various components of the immune system. As with other constitutional disorders, next-generation sequencing (NGS) is a powerful tool for the diagnosis of these diseases. While NGS can provide molecular confirmation of disease in a patient with a suspected or classic phenotype, it can also identify new molecular defects of the immune system, expand gene-disease phenotypes, clarify mechanism of disease, pattern of inheritance or identify new gene-disease associations. Multiple clinical specialties are involved in the diagnosis and management of patients with IEI, and most have no formal genetic training or expertise. To effectively utilize NGS tools and data in clinical practice, it is relevant and pragmatic to obtain a modicum of knowledge about genetic terminology, the variety of platforms and tools available for high-throughput genomic analysis, the interpretation and implementation of such data in clinical practice. There is considerable variability not only in the technologies and analytical tools used for NGS but in the bioinformatics approach to variant identification and interpretation. The ability to provide a molecular basis for disease has the potential to alter therapeutic management and longer-term treatment of the disease, including developing personalized approaches with molecularly targeted therapies. This review is intended for the clinical specialist or diagnostic immunologist who works in the area of inborn errors of immunity, and provides an overview of the need for genetic testing in these patients (the "why" aspect), the various technologies and analytical approaches, bioinformatics tools, resources, and challenges (the "how" aspect), and the clinical evidence for identifying which patients might be best served by such testing (the "when" aspect).

According to the manufacturer’s I-V data, we need to obtain the best parameters for assessing the photovoltaic systems. Although much work has been done in this area, it is still challenging to extract model parameters accurately. An efficient solver called SFLBS is developed to deal with this problem, in which an inheritance mechanism based on crossover and mutation is introduced. Specifically, the memory pool for storing historical population information is designed. During the sub-population evolution, the historical population will cross and mutate with the contemporary population with a certain probability, ultimately inheriting information about the dimensions that perform well. This mechanism ensures the population’s quality during the evolution process and effectively improves the local search ability of traditional SFLA. The proposed SFLBS is applied to extract unknown parameters from the single diode model, double diode model, three diode model, and photovoltaic module model. Based on the experimental results, we found that SFLBS has considerable accuracy in extracting the unknown parameters of the PV system problem, and its convergence speed is satisfactory. Moreover, SFLBS is used to evaluate three commercial PV modules under different irradiance and temperature conditions. The experimental results demonstrate that the performance of SFLBS is outstanding compared to some state-of-the-art competing algorithms. Moreover, SFLBS is still a reliable optimization tool despite the complex external environment. This research is supported by an online service for any question or needs to supplementary materials at https://aliasgharheidari.com .

Kin selection plays a major role in the evolution of cooperative systems. However, many social species exhibit complex within-group relatedness structures, where kin selection alone cannot explain the occurrence of cooperative behaviour. Understanding such social structures is crucial to elucidate the evolution and maintenance of multi-layered cooperative societies. In lamprologine cichlids, intragroup relatedness seems to correlate positively with reproductive skew, suggesting that in this clade dominants tend to provide reproductive concessions to unrelated subordinates to secure their participation in brood care. We investigate how patterns of within-group relatedness covary with direct and indirect fitness benefits of cooperation in a highly social vertebrate, the cooperatively breeding, polygynous lamprologine cichlid Neolamprologus savoryi. Behavioural and genetic data from 43 groups containing 578 individuals show that groups are socially and genetically structured into subgroups. About 17% of group members were unrelated immigrants, and average relatedness between breeders and brood care helpers declined with helper age due to group membership dynamics. Hence the relative importance of direct and indirect fitness benefits of cooperation depends on helper age. Our findings highlight how both direct and indirect fitness benefits of cooperation and group membership can select for cooperative behaviour in societies comprising complex social and relatedness structures. This article is protected by copyright. All rights reserved.

The timing of pubertal development is strongly influenced by the genetic background, and clinical presentations of delayed puberty are often found within families with clear patterns of inheritance. The discovery of the underlying genetic regulators of such conditions, in recent years through next generation sequencing, has advanced the understanding of the pathogenesis of disorders of pubertal timing and the potential for genetic testing to assist diagnosis for patients with these conditions. This review covers the significant advances in the understanding of the biological mechanisms of delayed puberty that have occurred in the last two decades.

Network pruning has been known to produce compact models without much accuracy degradation. However, how the pruning process affects a network’s robustness and the working mechanism behind remain unresolved. In this work, we theoretically prove that the sparsity of network weights is closely associated with model robustness. Through experiments on a variety of adversarial pruning methods, image-classification models and datasets, we find that weights sparsity will not hurt but improve robustness, where both weights inheritance from the lottery ticket and adversarial training improve model robustness in network pruning. Based on these findings, we propose a novel adversarial training method called inverse weights inheritance, which imposes sparse weights distribution on a large network by inheriting weights from a small network, thereby improving the robustness of the large network.

Anticipation is an inheritance pattern where disease severity increases and/or age of onset decreases in successive generations. It has been documented in neurodegenerative disorders [1,2], autoimm...

Mental illness remains the greatest chronic health burden globally with few in-roads having been made despite significant advances in genomic knowledge in recent decades. The field of psychiatry is constantly challenged to bring new approaches and tools to address and treat the needs of vulnerable individuals and subpopulations, and that has to be supported by a continuous growth in knowledge. The majority of neuropsychiatric symptoms reflect complex gene-environment interactions, with epigenetics bridging the gap between genetic susceptibility and environmental stressors that trigger disease onset and drive the advancement of symptoms. It has more recently been demonstrated in preclinical models that epigenetics underpins the transgenerational inheritance of stress-related behavioural phenotypes in both paternal and maternal lineages, providing further supporting evidence for heritability in humans. However, unbiased prospective studies of this nature are practically impossible to conduct in humans so preclinical models remain our best option for researching the molecular pathophysiologies underlying many neuropsychiatric conditions. While rodents will remain the dominant model system for preclinical studies (especially for addressing complex behavioural phenotypes), there is scope to expand current research of the molecular and epigenetic pathologies by using invertebrate models. Here, we will discuss the utility and advantages of two alternative model organisms-Caenorhabditis elegans and Drosophila melanogaster-and summarise the compelling insights of the epigenetic regulation of transgenerational inheritance that are potentially relevant to human psychiatry.

The major advances in genetic neuromuscular disorders in the last 30 years have been: (a) identification of the genetic basis for hundreds of these disorders, (b) through knowing the genes, understanding their pathobiology and (c) subsequent implementation of evidence-based treatments for some of the disorders. New genomic technologies are providing precision diagnosis, mode of inheritance and likely prognosis for more patients than ever before. Parents of children with a genetic diagnosis can then use preimplantation or prenatal diagnosis to avoid having further affected children if they wish. But is this the best we can do for genetic neuromuscular disorders? Since the 1980s, it has been argued it would be better to identify Duchenne muscular dystrophy carrier mothers, rather than diagnose their affected sons. Carrier screening for recessive disorders can identify couples with a high chance of having affected children. It allows couples reproductive choice and can prevent infant morbidity and mortality and significant distress for families. Professional bodies in many countries now recommend prospective parents should be informed about carrier screening. Implementing and funding expensive therapies increases the cost-effectiveness of carrier screening, increasing its attractiveness to governments. Best practice for genetic neuromuscular disorders should include equitable access to carrier screening.

The reduction of excessive weight remains a major public health challenge, with control currently limited to a calorie reduction strategy. Currently, attempts are being made at revisiting the fibre hypothesis based on the African studies of Denis Burkitt, that the lack of dietary fibre in the modern diet was responsible for the occurrence of obesity and many of the other non-communicable diseases of what he called “Western civilization”. However, the dilemma is that Burkitt himself stressed that other peoples of his day, such as the Maasai, remained healthy without consuming such high fibre diets. Equally, the present obesity epidemic is accompanied by diseases of a malfunctioning immune system and of poor mental health that do not seem to be adequately explained simply by a deficiency of dietary fibre. Though unknown in Burkitt’s day, an increasing degradation of a mutualistic intestinal microbiome would offer a better fit to the observed epidemiology, especially if the microbiome is not effectively passed on from mother to child at birth. Taking the broader view, in this article we posit a view of the microbiome as a cofactor of mammalian evolution, in which a maternal microbial inheritance complements the parental genetic inheritance of the animal, both engaging epigenetic processes. As this would require the microbiome to be fully integrated with the animal as it develops into an adult, so we have a meaningful evolutionary role for the microbiome–gut–brain axis. By a failure to correctly establish a microbiome–gut interface, the inhibition of maternal microbial inheritance sets the scene for the future development of non-communicable disease: compromised immune system function on the one hand and dysfunctional gut–brain communication on the other. The basic principle is that the fully functioning, diverse, microbiome achieves interkingdom communication by the generation of messenger chemicals, semiochemicals. It is envisaged that the in situ detection of these as yet ill-defined chemical entities by means of an ingestible sensor would indicate the severity of disease and provide a guide as to its amelioration.

More than a century ago, August Weissman defined a distinction between the germline (responsible for propagating heritable information from generation to generation) and the perishable soma. A central motivation for this distinction was to argue against the inheritance of acquired characters, as the germline was partly defined by its protection from external conditions. However, recent decades have seen an explosion of studies documenting the intergenerational and transgenerational effects of environmental conditions, forcing a re-evaluation of how external signals are sensed by, or communicated to, the germline epigenome. Here, motivated by the centrality of small RNAs in paradigms of epigenetic inheritance, we review across species the myriad examples of intercellular RNA trafficking from nurse cells or somatic tissues to developing gametes.

Understanding the patterns of microevolutionary processes involves a wide range of population genetic studies on different species. However, the number of genetically studied species is limited due to significant methodological difficulties in testing the genetic conditionality of various traits. Developing population phenetics may become an alternative, which allows considering a large number of new species subject to development of morphologically and genetically-based system to describe the variability and classification of phenotypic traits. Gastropods are a classic object for carrying out population genetic studies based on the analysis of polymorphism of shell coloration. The parametric classification system proposed by S. Sergievsky et al. (1995) for periwinkles of the genus Littorina may serve as a basis for the developing of a universal system for classifying color traits for that taxonomic group. Since a large amount of new data has been published in recent years, this system requires correction and revision. The study aims to revise the system, taking into account new material on the pigment composition, as well as on the peculiarities of the formation and inheritance of color traits, their joint occurrence, etc. A revised and modified classification system for shell coloration traits is presented by the example of the White Sea gastropods L. obtusata; this system considers the idea of the formation of a phenotype as a combination of several elementary traits. These are traits associated with the formation of: 1) a shell background color (the ability to include different pigments in the ostracum and the hypostracum color); 2) a pattern of spots (the presence of inclusions of white and/or brown pigment); and 3) wide longitudinal bands (brown, white, and orange). Elementary traits are highlighted taking into account the pigments involved, as well as the mechanisms of their formation and inheritance. When describing the shell coloration, elementary traits are first used to describe relatively simple traits (groups of phenes “Shell background color”, “Hypostracum color”, “Pattern of spots”, and “Wide longitudinal bands”), which are subsequently combined to describe the phenotype as a whole. Our study provides an overview of the available data on the qualitative composition of shell pigments in periwinkles and patterns of formation and inheritance of color traits; their possible combinations are described. The phenes isolated by us are described together with their occurrence, color specification in the RGB system, and the peculiarities of the formation, taking into account the distribution of pigments in the shell. Visible traits, that may be used to assess the distribution of pigments in the shell, are indicated. The ontogenetic changes in traits are described. Despite the fact that the proposed classification system is developed by the example of L. obtusata, it can be used for same purposes for other periwinkle species and, with some modifications, for a wide range of gastropod species.

Pigmentation divergence between Drosophila species has emerged as a model trait for studying the genetic basis of phenotypic evolution, with genetic changes contributing to pigmentation differences often mapping to genes in the pigment synthesis pathway and their regulators. These studies of Drosophila pigmentation have tended to focus on pigmentation changes in one body part for a particular pair of species, but changes in pigmentation are often observed in multiple body parts between the same pair of species. The similarities and differences of genetic changes responsible for divergent pigmentation in different body parts of the same species thus remain largely unknown. Here we compare the genetic basis of pigmentation divergence between Drosophila elegans and D. gunungcola in the wing, legs, and thorax. Prior work has shown that regions of the genome containing the pigmentation genes yellow and ebony influence the size of divergent male-specific wing spots between these two species. We find that these same two regions of the genome underlie differences in leg and thorax pigmentation; however, divergent alleles in these regions show differences in allelic dominance and epistasis among the three body parts. These complex patterns of inheritance can be explained by a model of evolution involving tissue-specific changes in the expression of Yellow and Ebony between D. elegans and D. gunungcola.

High-throughput DNA sequencing is increasingly employed to diagnose single gene neurological and neuromuscular disorders. Large volumes of data present new challenges in data interpretation and its useful translation into clinical and genetic counselling for families. Even when a plausible gene is identified with confidence, interpretation of the clinical significance and inheritance pattern of variants can be challenging. We report our approach to evaluating variants in the skeletal muscle chloride channel ClC-1 identified in 223 probands with myotonia congenita as an example of these challenges. Sequencing of CLCN1, the gene that encodes CLC-1, is central to the diagnosis of myotonia congenita. However, interpreting the pathogenicity and inheritance pattern of novel variants is notoriously difficult as both dominant and recessive mutations are reported throughout the channel sequence, ClC-1 structure-function is poorly understood and significant intra- and interfamilial variability in phenotype is reported. Heterologous expression systems to study functional consequences of CIC-1 variants are widely reported to aid the assessment of pathogenicity and inheritance pattern. However, heterogeneity of reported analyses does not allow for the systematic correlation of available functional and genetic data. We report the systematic evaluation of 95 CIC-1 variants in 223 probands, the largest reported patient cohort, in which we apply standardized functional analyses and correlate this with clinical assessment and inheritance pattern. Such correlation is important to determine whether functional data improves the accuracy of variant interpretation and likely mode of inheritance. Our data provide an evidence-based approach that functional characterization of ClC-1 variants improves clinical interpretation of their pathogenicity and inheritance pattern, and serve as reference for 34 previously unreported and 28 previously uncharacterized CLCN1 variants. In addition, we identify novel pathogenic mechanisms and find that variants that alter voltage dependence of activation cluster in the first half of the transmembrane domains and variants that yield no currents cluster in the second half of the transmembrane domain. None of the variants in the intracellular domains were associated with dominant functional features or dominant inheritance pattern of myotonia congenita. Our data help provide an initial estimate of the anticipated inheritance pattern based on the location of a novel variant and shows that systematic functional characterization can significantly refine the assessment of risk of an associated inheritance pattern and consequently the clinical and genetic counselling.

Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.

DNA is central to the propagation and evolution of most living organisms due to the essential process of its self-replication. Yet it also encodes factors that permit epigenetic (not included in DNA sequence) flow of information from parents to their offspring and beyond. The known mechanisms of epigenetic inheritance include chemical modifications of DNA and chromatin, as well as regulatory RNAs. All these factors can modulate gene expression programs in the ensuing generations. The nematode Caenorhabditis elegans is recognized as a pioneer organism in transgenerational epigenetic inheritance research. Recent advances in C. elegans epigenetics include the discoveries of control mechanisms that limit the duration of RNA-based epigenetic inheritance, periodic DNA motifs that counteract epigenetic silencing establishment, new mechanistic insights into epigenetic inheritance carried by sperm, and the tantalizing examples of inheritance of sensory experiences. This review aims to highlight new findings in epigenetics research in C. elegans with the main focus on transgenerational epigenetic phenomena dependent on small RNAs.

Prime editing enables efficient introduction of targeted transversions, insertions, and deletions in mammalian cells and several organisms. However, genetic disease models with base deletions by prime editing have not yet been reported in mice. Here, we successfully generate a mouse model with a cataract disorder through microinjection of prime editor 3 (PE3) plasmids to efficiently induce targeted single-base deletion. Notably, a generated mouse with a high G-deletion rate (38.2%) displays a nuclear cataract phenotype; the PE3-induced deletions in mutant mice achieve high rates of germline transmission to their progenies, with phenotypic inheritance of cataract. Our data propose that modeling a genetic disease with a single nucleotide deletion in mice can be achieved with prime genome editing in vivo., Graphical abstract, Lin et al. use the prime editing system to introduce a G-deletion into Crygc and successfully establish a mouse model with a cataract disorder, which can be transmitted to the next generation.

Advances in recombinant DNA approaches have resulted in the development of transgene architectures that severely bias their own inheritance, a process commonly referred to as "gene drive." The rapid pace of development, combined with the complexity of many gene drive approaches, threatens to overwhelm those responsible for ensuring its safe use in the laboratory, as even identifying that a specific transgene is capable of gene drive may not be intuitive. Although currently gene drive experiments have been limited to just a few species (mosquitoes, flies, mice, and yeast), the range of organisms used in gene drive research is expected to increase substantially in the coming years. Here the defining features of different gene drive approaches are discussed. Although this will start with a focus on identifying when gene drive could or could not occur, the emphasis will also be on establishing risk profiles based on anticipated level of invasiveness and persistence of transgenes in the surrounding environment. Attention is also called to the fact that transgenes can be considered invasive without being considered gene drive (and vice versa). This further supports the notion that adequate risk assessment requires information regarding the specific circumstances a given transgene or set of transgenes is capable of invading a corresponding population. Finally, challenges in the review and evaluation of work involving gene drive organisms are discussed.

Brown blotch disease caused by Colletotrichum capsici, is one of the most important disease affecting cowpea production in Burkna Faso. Every year the disease can cause yield losses as high as 42 to 100% on farmer’s fileds. This study aimed to understand the inheritance of its resistance in cowpea and also identify quantitative trait loci (QTL) associated with the resistance. Seedlings of parents and F1, F2 and BC1F1 progenies from crosses involving four susceptible and four resistant parents were screened in greenhouse conditions for brown blotch disease reaction. The inheritance studies indicated that different genes action were involved in the resistance of brown blotch resistance disease. In KN-1 variety, two or several genes associated to brown blotch were suggested. In Donsin local, a partially dominant gene, Rcc1, would be associated with the resistance. In Moussa local, a single major dominant gene, Rcc2, was identified. A single major recessive gene, rcc2, was found to control resistance with brown blotch in the cowpea resistant variety IT93K-503/46-13. The research of gene or QTL associated with brown blotch in cowpea variety KN-1 has been investigated. Polymorphic single nucleotide polymorphisms (SNP) markers and QTL associated to brown blotch resistance were discovered from 63 F2 individuals from a cross involving the susceptible variety Tiligre and the resistant KN-1. More than 11800 polymorphic SNP markers covered 1019.3 cM of the whole genome of cowpea were identified. A single dominant QTL, nomed qBBDR2 and 102 individual SNP markers tightly associated with the resistance of C. capsici were identified on chromosome 2 (Phytozome) of the cowpea genome. Key word: Cowpea, Colletotrichum capsici, resistance, inheritance, single nucleotide polymorphisms (SNP) marker, QTL.

Hereditary leiomyomatosis is a genetic disorder that follows an autosomal dominant pattern of inheritance. Along with a variety of leiomyomas, affected individuals are predisposed to developing an aggressive form of type 2 papillary renal malignancy known as Hereditary Leiomyomatosis Associated Renal Cell Carcinoma (HLRCC) that can occur in both the tubulo-papillary and collecting-duct systems. We present a rare case of HLRCC with components of urothelial carcinoma. The patient was treated with cisplatin-based neoadjuvant chemotherapy followed by left radical nephroureterectomy to achieve complete remission of disease.

Objective Congenital hypothyroidism (CH) is known to be due to thyroid dyshormonogenesis (DH), which is mostly inherited in an autosomal recessive inheritance pattern or thyroid dysgenesis (TD), whose inheritance pattern is controversial and whose molecular etiology remains poorly understood. Design and methods The variants in 37 candidate genes of CH, including 25 genes related to TD, were screened by targeted exon sequencing in 205 Chinese patients whose CH cannot be explained by biallelic variants in genes related to DH. The inheritance pattern of the genes was analyzed in family trios or quartets. Results Of the 205 patients, 83 patients carried at least one variant in 19 genes related to TD, and 59 of those 83 patients harbored more than two variants in distinct candidate genes for CH. Biallelic or de novo variants in the genes related to TD in Chinese patients are rare. We also found nine probands carried only one heterozygous variant in the genes related to TD that were inherited from a euthyroid either paternal or maternal parent. These findings did not support the monogenic inheritance pattern of the genes related to TD in CH patients. Notably, in family trio or quartet analysis, of 36 patients carrying more than two variants in distinct genes, 24 patients carried these variants inherited from both their parents, which indicated that the oligogenic inheritance pattern of the genes related to TD should be considered in CH. Conclusions Our study expanded the variant spectrum of the genes related to TD in Chinese CH patients. It is rare that CH in Chinese patients could be explained by monogenic germline variants in genes related to TD. The hypothesis of an oligogenic origin of the CH should be considered.

A study was conducted to determine the mode of inheritance for grain shape and aroma traits of lines in the Uganda rice germplasm. Five aromatic and four non-aromatic rice lines were crossed in screen house using North Carolina Design II at the National Crops Resources Research Institute, Uganda. The resulting F2 seeds and their parents were planted in the field using complete randomized block design in two replications. The grain shape and aroma intensity of the harvested F3 seeds on per hill basis were determined in laboratory using instrumental and sensory evaluation procedures, respectively. The results revealed that the inheritance of grain shape and aroma traits were influenced by both additive and non-additive gene actions, but with the grain shape being dominated by additive gene action and the aroma by non-additive gene action. In addition, Supa 3, Supa 5 and Supa 1052 rice lines exhibited good general combining ability effects for the shape trait while Supa 3 and MET 13 were good general combiners for the aroma trait. The superior cross combination from Supa 3 x Supa 5 for grain shape and Supa 3 x MET 13 for aroma trait could be used for selection of the relevant traits at advanced stages of the breeding cycles. Key words: General combining ability effects, gene action, North Carolina design II, selection, sensory evaluation.

Obesity is a complex and heterogeneous disorders characterized by excessive body mass and fat and determined by genes, environmental factors and also the interaction between genes and environment. With an increased incidence in children and a prevalence of up to 25% in some countries, obesity is becoming a clinical and public problem of increasing importance in modern society. Thus, in this review the causes of obesity in particular the genetic causes will be discussed.

The human genome studies reveal that most of the diseases have a genetic component. Genetic mutation occurs either randomly or due to an environmental factor. Genetic disorders may or may not be hereditary. WHO data illustrate that the congenital anomalies are the reason for 17%–43% of infant mortality. If parent’s genetic configuration is vulnerable to some diseases, their children and grandchildren are more susceptible to such illness. This suggests that their genes or chromosomes possess aberrant changes and are carried over into next generation and results in congenital or hereditary diseases. Ancient ayurvedic acharyas had the idea that the genetic materials are transmitted from generation to generation. The expression of these can be understood with regard to prakriti. An individual’s unique physical characteristics and psychic behaviors (phenotype) depends on the prakriti. Genetics emerged in mid to late 19th Century. But centuries before itself, ancient Ayurvedic literature documented the union of sukra and shonita, concept of beeja, beejabhaga and beejabhagavayava, inheritance, congenital anomalies, and genetic disorders. Ayurveda also gave importance to personalized or individualized concepts of understanding and treating diseases. Ayurvedic concepts like garbhasambhavasamagri (factors necessary for formation of garbha) and garbhotpadaka bhava (six procreating factors), dinacharya, ritucharya, sadvritha, dharaneeya, adharaneeyavega, ritumaticharya, & garbhinicharya assures the regulation of gene sequencing and gene expression and thus can-do wonders to the challenging issues.

Mother knows best Inheritance of social status, and its associated costs and benefits, is well demonstrated in humans. Whether such an intergenerational system occurs in other species is harder to demonstrate. Ilany et al. looked at nearly 30 years of social interaction data in spotted hyenas, a female-dominated system with a highly structured society, and found that status inheritance is just as prominent (see the Perspective by Firth and Sheldon). Juvenile hyenas had social associations that were similar to their mothers, and the strength of the association was higher for higher-status mothers. Importantly, survival was associated with social inheritance, suggesting that these social roles are essential to hyena life. Science , abc1966, this issue p. 348 ; see also abj5234, p. 274

BACKGROUND Hordeum glaucum Steud. is an important grass weed species in South Australia that has evolved resistance to glyphosate. This study investigated the mode of inheritance of glyphosate resistance in this species. RESULTS Hand-pollination of glyphosate susceptible and resistant populations generated two F1 individuals, selfed to yield F2 progenies. In dose-response experiments, the F2 progenies showed intermediate response between the two parent populations. High variation in EPSPS gene copies was observed among F2 individuals, with some individuals possessing more gene copies than the resistant parent population. No evidence of a Mendelian single-gene pattern of inheritance was observed. CONCLUSION Inheritance of gene amplification in H. glaucum is non-Mendelian. © 2021 Society of Chemical Industry.

For the analysis of the results of hybridization during the early stages of wheat breeding, it is important to choose a system of traits by which the selection of elite plants will achieve some genetic progress and lead to improved yield potential. As a rule, when analyzing various factorial traits in the first-generation hybrids, quantitative parameters of plant yield components, their inheritance pattern, and heterosis are determined. A new source material of spring durum wheat was created by intraspecific and interspecific crossings. The inheritance pattern of the main components of spike productivity in the first-generation hybrids of durum wheat has been studied. The inheritance overdominance and partial positive dominance of spike length and grain number per spike was characteristic for the majority (64.3%) of intraspecific F1 hybrids. The best hybrid combination (Melanopus 10-02 × Slavuta) was characterized by overdominance and positive dominance in the inheritance of all the studied traits; high degree of heterosis (DH) (64.7%) by grain weight per spike was noted. Heterosis and inheritance pattern of the “1000 grain weight” trait by overdominance was found in hybrids obtained by crossing Melanopus 10-02 × Slavuta (hp = +5.0; DH +9.9%), Leucurum 06-07 × Saratovskaya zolotistaya (hp = +13.0; DH +7.4%), and Leucurum 06-07 × Kharkivska 29 (hp = +17.0; DH +10.0%). Among the studied parental component, the line Melanopus 10-02 has been selected and submitted to the State Qualifying Examination of the Ukrainian Institute for Plant Variety Examination. It was registered as the novel durum wheat cultivar MІР Raiduzhna. The promising perspective of the intraspecific cross combination (Line 08-17 × Saratovskaya zolotistaya) was noted; these hybrids were characterized by heterosis for all the analyzed traits and overdominance of their inheritance, which allowed recommending this cross for further genetic studies. Therefore, defining the parameters of plant productivity, the inheritance pattern, the degree of heterosis in the first-generation hybrids is an urgent task in creating new varieties as well as in the predicting breeding and genetic effect of crossing.

Populations of rigid ryegrass (Lolium rigidum Gaudin) from southern Australia have evolved resistance to the thiocarbamate herbicide prosulfocarb. The inheritance of prosulfocarb resistance was explored by crossing resistant (R) and susceptible (S) individuals. In all families within each cross, except 16.2, the response of the F1 was intermediate between the parents, suggesting that resistance is inherited as a single, partially dominant trait. For 16.2, the response of the F1 was more similar to the S parent, suggesting resistance may be a recessive trait in this population. Segregation at the discriminating dose of 1,200 g ai ha−1 prosulfocarb in population 375-14 fit the ratio (15:1) consistent with two independent dominant alleles; in population 198-15, it fit a ratio (13:3) for two independent alleles, one dominant and one recessive; and in population EP162, it fit a ratio (9:7) for two additive dominant alleles. In contrast, segregation of population 16.2 fit a ratio (7:9) consistent with two independent recessive alleles contributing to prosulfocarb resistance. Four different patterns of resistance to prosulfocarb were identified in different R populations, with inheritance as a dominant allele, dominant and recessive, additive dominant and as an independent recessive allele. This suggests there are several different mechanisms of prosulfocarb resistance present in L. rigidum.

Congenital optic disc pits (ODPs) are well-circumscribed depressions within the optic disc. Thought to arise from anomalous closure of the optic fissure during embryonic development, they are now considered to lie on a broader spectrum of congenital optic disc anomaly (CODA). An increasing number of reports describe clustering of these cases within families, suggesting that inherited genetic elements play a role in disease predisposition. Here, we highlight the clinical features of 2 sets of father-son pairs affected with ODPs and provide preliminary molecular genetic analysis. Subjects underwent complete ophthalmological examination and imaging. In addition, whole-exome sequencing was carried out following informed consent. The resulting datasets were examined for potentially causal genetic variants, both in genes already known to be linked to CODA as well as those likely to lie in the same or similar genetic pathways. In this instance, no unambiguously causal variants were identified. This case series highlights the familial inheritance of ODPs, adding to the existing body of literature supporting an underlying genetic cause for this rare clinical entity. The inclusion here of specific molecular findings raises the hope that the genetic pathophysiology underlying rare entities like ODPs might be clarified in the future by the addition of similarly molecular-documented reports.

The inheritance of substance abuse, including opioid abuse, may be influenced by genetic and non-genetic factors related to the environment, such as stress and socioeconomic status. These non-genetic influences on the heritability of a trait can be attributed to epigenetics. Epigenetic inheritance can result from modifications passed down from the mother, father, or both, resulting in either maternal, paternal, or parental epigenetic inheritance, respectively. These epigenetic modifications can be passed to the offspring to result in multigenerational, intergenerational, or transgenerational inheritance. Human and animal models of opioid exposure have shown generational effects that result in molecular, developmental, and behavioral alterations in future generations.

Common beans are an important nutritious food crop to many people in developing countries. Inadequate soil-P is one of the major constraints to high bean seed yield productivity. Information about genetic effects that control inheritance of root traits in common bean grown under low soil-P conditions is scarce, and that is a challenge for genetic enhancement. This study was therefore implemented to determine inheritance and gene action of root traits in common bean for tolerance to low soil-P. The six generations were evaluated in a completely randomised design with two replicates under low soil-P in a pot experiment. Generation mean analysis revealed that both allelic and non-allelic genetic interactions controlled inheritance of root traits studied. Cumulative main gene effect was higher than epistasis effects. Additive genetic effects were more predominant than dominance effects. Additive and additive × dominance epistatic gene effects were more important in controlling inheritance of root traits under low soil-P. Broad-sense heritability for hypocotyl root number was the highest (93.98 %) while the narrow-sense heritability was moderate (51.13 %). To develop improved genotypes tolerant to low soil-P, recombination crossing should be followed by screening and selection in later generations for high seed yield, root and other preferred traits. Key words: Common bean, inheritance, genotype, gene effect, heritability, low soil-P.

Observational results suggest that environment has a great impact on physiology but these phenomena cannot be explained by genetic mechanisms alone. The epigenetic studies broadens our knowledge about development and physiology. Currently, the topical issues are transgenerational effects which imply transmission through generations both genetic and phenotypic adaptive mechanisms. The accumulated data indicate that the influence of environmental factors (bad habits, stress, excessive or insufficient nutrition, microbiota and others) at early stages of development can contribute to the epigenetic transgenerational inheritance of phenotypic variability. Epigenetic processes can alter gene expression, which in turn can either increase vulnerability or contribute to the development of disease tolerance in future generations. Epigenetic biomarker signatures can be considered as a future diagnostic tool for assessing person’s specific susceptibility to disease or exposure to environmental toxicants. The current review discusses the molecular genetic mechanisms of transgenerational inheritance and the influence of various risk factors.

It is well established that environmental exposures can modify the profile of heritable factors in an individual's germ cells, ultimately affecting the inheritance of phenotypes in descendants. Similar to exposures, an ancestor's genotype can also affect the inheritance of phenotypes across generations, sometimes in offspring who do not inherit the genetic aberration. This can occur via a variety of prenatal, in utero, or postnatal mechanisms. In this review, we discuss the evidence for this process in mammals, with a focus on examples that are potentially mediated through the germline, while also considering alternate routes of inheritance. Noninherited ancestral genotypes may influence descendant's disease risk to a much greater extent than currently appreciated, and focused evaluation of this phenomenon may reveal novel mechanisms of inheritance. Summary sentence This is a review of the evidence that non-inherited ancestral alleles can influence the phenotypes of descendants via a variety of mechanisms including germline, in utero, and postnatal processes. Graphical Abstract

Growth habit is a plant architectural trait in grain legumes with no exception of horse gram [Macrotyloma uniflorum (Lam.) Verdc.]. Determinacy and indeterminacy are the two types of growth habits reported in horse gram. Relative advantages of the two types of growth habit depend on the production systems to which cultivars are targeted. Dependable information on genetics of growth habit provide clues for adopting the most appropriate selection strategy to breed high yielding horse gram varieties with desired growth habit. Taking cues from the past studies, we hypothesize that growth habit in horse gram is controlled by two genes displaying inhibitory epistasis and indeterminacy is dominant over determinacy. To test this hypothesis, we monitored the inheritance of growth habit in F1, F2 and F3 generations derived from two crosses involving parents differing for growth habit. Contrary to our hypothesis, determinate growth habit of F1s of both the crosses suggested dominance of determinacy over indeterminacy. A good fit of observed segregation of F2 plants to that of the hypothesized segregation in the ratio of 13 determinate: 3 indeterminate plants, besides confirming dominance of determinacy, suggested classical digenic inhibitory epistatic control of growth habit. These results were further confirmed in F3 generation based on goodness of fit between observed numbers of plants segregating for determinacy and indeterminacy and those expected in the ratio of 49 determinate: 15 indeterminate plants. To the best of our knowledge, this is the first report on the inheritance of growth habit in horse gram.

Since the appearance of the scientific approach to Darwinian medicine in 1991, the study of disease, especially infectious diseases have deserved to be treated from an evolutionary approach. In this sense, viruses, the cause of new epidemics and pandemics have also deserved to be studies from an evolutionary approach. Our genome has abundant genetic information that viruses have left us as fingerprints. It has already been demonstrated that viruses evolve by natural selection, starting mainly from their mutations and this is the proposal based on Darwin's legacy;however, there is also the mechanism of horizontal gene transfer between viruses, especially RNAs, and between the host and viruses. This knowledge is based on the adaptive theory, so called theory of inheritance of acquired characters, proposed by Lamarck and supported by the epigenetics. The appearance of SAR-CoV-2 has not been excluded from its evolutionary origin being studied and for this reason, the present word is based on an updated bibliographic review on the origin of this virus, having concluded that they participated in this process both the mechanisms of natural selection and acquired characters. A better understanding of these evolutionary mechanisms could serve to prevent future occurrences of new viral epidemics.

Ukazanie powiązań między genotypem a fenotypem jest problematyczne nie tylko ze względu na ogromną złożoność interakcji między genami, białkami i funkcjami fizjologicznymi wyższych rzędów, ale również dlatego, że paradygmatom przyczynowości genetycznej w systemach biologicznych towarzyszy duże zamieszanie. W tym artykule przeanalizuję niektóre związane z tym błędne przekonania, zaczynając od zagadnienia definicji genu. W toku rozwoju biologii uległa ona zasadniczej zmianie - pierwotnie gen rozumiano jako przyczynę cech fenotypowych, obecnie definiuje się go jako fragment DNA. Następnie przejdę do następujących zagadnień: czy "cyfrowa" natura sekwencji DNA gwarantuje im pierwszeństwo w ciągu przyczynowym w porównaniu z dziedzicznością niezwiązaną z DNA, czy koncepcja programów genetycznych jest sensowna i użyteczna oraz jaka jest rola przyczynowości na wyższych poziomach (przyczynowości odgórnej). Metafory, które dobrze spełniały swoją funkcję podczas molekularnej fazy rozwoju biologii w ostatnich dziesięcioleciach, mają ograniczone zastosowanie w wielopoziomowym świecie biologii systemowej, a nawet mogą pro-wadzić do nieporozumień. Wyjaśnienie wieloczynnikowej przyczynowości genetycznej związanej z funkcjami fizjologicznymi wyższych rzędów wymaga nowych paradygmatów, które zarazem pozwolą zrozumieć zjawiska badane pierwotnie przez genetykę. Modelowanie funkcji biologicznych umożliwia rozwiązanie "problemu genetycznego efektu różnicowego" i odegra istotną rolę również w wyjaśnieniu przyczynowości genetycznej.