Genetic Benefits Research Articles

Genotyping by sequencing; a strategy for identification and mapping of induced mutation in newly developed wheat mutant lines.

Exposing genetic material with physical mutagens can create novel genetic resources capable of combating different stresses. High throughput GBS-DArTseq™ assay was deployed to estimate genetic diversity of 33 newly developed stable wheat mutants as compared to the wild type. The identified 1,57,608 PAVs markers were randomly distributed across wheat chromosomes and sub-genomes with the highest number detected on Chr-7D (2877) and Chr-7B (2711). The B sub-genome contained the most PAVs followed by D and A-sub genome. Among mutant lines, Pb-M-2061 and Pb-M-59 had the highest PAV count, while Pb-M-605 and Pb-M-196 had the lowest. A total of 7,910 PAVs were consistently present over all replicates, with 3,252 specifically present in mutants and absent in wild type. The maximum PAVs (1480) were found in Pb-M-1027 and Pb-M-1323 (656). Functional characterization revealed that out of 3,252, 1,238 were found in wheat transcriptome database that contained 152 characterized and 1,196 uncharacterized genes. COGs and GO-terms analysis linked many PAVs with pathways involving signaling, metabolism and defense. Maximum number of gene-containing PAVs were identified in Pb-M-1027, Pb-M-2302 and Pb-M-1323 which were involved in tolerance to diseases and abiotic stresses, improved photosynthetic efficiency, larger grain size, increased grain yield and harvest index pathways. This study provides valuable insights into the genetic diversity and potential agronomic benefits of PAVs in wheat mutant lines. These findings can help molecular geneticist and breeders for exploiting the induced genetic diversity for unravelling the genetic circuits as well as exploiting in wheat breeding for developing resilient cultivars.

Conditional protein splicing of the Mycobacterium tuberculosis RecA intein in its native host

The recA gene, encoding Recombinase A (RecA) is one of three Mycobacterium tuberculosis (Mtb) genes encoding an in-frame intervening protein sequence (intein) that must splice out of precursor host protein to produce functional protein. Ongoing debate about whether inteins function solely as selfish genetic elements or benefit their host cells requires understanding of interplay between inteins and their hosts. We measured environmental effects on native RecA intein splicing within Mtb using a combination of western blots and promoter reporter assays. RecA splicing was stimulated in bacteria exposed to DNA damaging agents or by treatment with copper in hypoxic, but not normoxic, conditions. Spliced RecA was processed by the Mtb proteasome, while free intein was degraded efficiently by other unknown mechanisms. Unspliced precursor protein was not observed within Mtb despite its accumulation during ectopic expression of Mtb recA within E. coli. Surprisingly, Mtb produced free N-extein in some conditions, and ectopic expression of Mtb N-extein activated LexA in E. coli. These results demonstrate that the bacterial environment greatly impacts RecA splicing in Mtb, underscoring the importance of studying intein splicing in native host environments and raising the exciting possibility of intein splicing as a novel regulatory mechanism in Mtb.

Multi-generational benefits of genetic rescue

Genetic rescue—an increase in population fitness following the introduction of new alleles—has been proven to ameliorate inbreeding depression in small, isolated populations, yet is rarely applied as a conservation tool. A lingering question regarding genetic rescue in wildlife conservation is how long beneficial effects persist in admixed populations. Using data collected over 40 years from 1192 endangered Florida panthers (Puma concolor coryi) across nine generations, we show that the experimental genetic rescue implemented in 1995—via the release of eight female pumas from Texas—alleviated morphological, genetic, and demographic correlates of inbreeding depression, subsequently preventing extirpation of the population. We present unequivocal evidence, for the first time in any terrestrial vertebrate, that genetic and phenotypic benefits of genetic rescue remain in this population after five generations of admixture, which helped increase panther abundance (> fivefold) and genetic effective population size (> 20-fold). Additionally, even with extensive admixture, microsatellite allele frequencies in the population continue to support the distinctness of Florida panthers from other North American puma populations, including Texas. Although threats including habitat loss, human-wildlife conflict, and infectious diseases are challenges to many imperiled populations, our results suggest genetic rescue can serve as an effective, multi-generational tool for conservation of small, isolated populations facing extinction from inbreeding.

Status on management of access to genetic resources, traditional knowledge and benefit sharing

The management of access to genetic resources, traditional knowledge (TK), and benefit sharing among indigenous people and local communities in the worldwide is extensively addressed in international legal instruments, including the Convention on Biological Diversity (CBD) and its Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits (ABS) Arising from their Utilization. The CBD aims to promote the conservation of biological resources, the sustainable use of biodiversity components and the equitable, fair sharing of benefits arising from the use of genetic resources. The Nagoya Protocol sets out core obligations for its contracting Parties to take measures in relation to ABS and compliance. In 2021, the Secretariats of the CBD released the first draft of the Post-2020 Global Biodiversity Framework with the mission for the period up to 2030, aiming towards the 2050 vision: “To take urgent action across society to conserve and sustainably use biodiversity and ensure the fair and equitable sharing of benefits from the use of genetics resources, to put biodiversity on a path to recovery by 2030 for the benefit of planet and people.” Therefore, capacity building and development for the implementation of the Nagoya Protocol are crucial, especially for developing countries. One of the most commonly identified new capacity building needs is digital sequence information on genetic resources and their roles in ABS. As a member of the CBD and the Nagoya Protocol, Vietnam has obligations to develop the National Strategy Framework on Biodiversity to 2030, with a vision to 2050, consistent with the requirements of the Post-2020 Global Biodiversity Framework, Protocols, and relevant Agreements. This includes developing recommendations on management of access to genetic resources and TK, as well as benefit sharing within the Draft of the National Biodiversity Strategy and Action Plan. This research aims to contribute to implement the Post-2020 Global Biodiversity Framework and the Nagoya Protocol in Vietnam by assessing the status of management regarding access to genetic resources, TK, and benefit sharing.

“It’s hard to wait”: Provider perspectives on current genomic care in safety-net NICUs

PurposeCritically ill infants from marginalized populations disproportionately receive care in neonatal intensive care units (NICUs) that lack access to state-of-the-art genomic care, leading to inequitable outcomes. We sought provider perspectives to inform our implementation study (VIGOR) providing rapid genomic sequencing within these settings. MethodsWe conducted semistructured focus groups with neonatal and genetics providers at 6 NICUs at safety-net hospitals, informed by the Promoting Action on Research Implementation in Health Services framework, which incorporates evidence, context, and facilitation domains. We iteratively developed codes and themes until thematic saturation was reached. ResultsRegarding evidence, providers felt that genetic testing benefits infants and families. Regarding context, the major barriers identified to genomic care were genetic testing cost, lack of genetics expertise for disclosure and follow-up, and navigating the complexity of selecting and ordering genetic tests. Providers had negative feelings about the current status quo and inequity in genomic care across NICUs. Regarding facilitation, providers felt that a virtual support model such as VIGOR would address major barriers and foster family-centered care and collaboration. ConclusionNICU providers at safety-net hospitals believe that access to state-of-the-art genomic care is critical for optimizing infant outcomes; yet, substantial barriers exist that the VIGOR study may address.

CRISPR-Based Gene Therapies: From Preclinical to Clinical Treatments.

In recent years, clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) protein have emerged as a revolutionary gene editing tool to treat inherited disorders affecting different organ systems, such as blood and muscles. Both hematological and neuromuscular genetic disorders benefit from genome editing approaches but face different challenges in their clinical translation. The ability of CRISPR/Cas9 technologies to modify hematopoietic stem cells ex vivo has greatly accelerated the development of genetic therapies for blood disorders. In the last decade, many clinical trials were initiated and are now delivering encouraging results. The recent FDA approval of Casgevy, the first CRISPR/Cas9-based drug for severe sickle cell disease and transfusion-dependent β-thalassemia, represents a significant milestone in the field and highlights the great potential of this technology. Similar preclinical efforts are currently expanding CRISPR therapies to other hematologic disorders such as primary immunodeficiencies. In the neuromuscular field, the versatility of CRISPR/Cas9 has been instrumental for the generation of new cellular and animal models of Duchenne muscular dystrophy (DMD), offering innovative platforms to speed up preclinical development of therapeutic solutions. Several corrective interventions have been proposed to genetically restore dystrophin production using the CRISPR toolbox and have demonstrated promising results in different DMD animal models. Although these advances represent a significant step forward to the clinical translation of CRISPR/Cas9 therapies to DMD, there are still many hurdles to overcome, such as in vivo delivery methods associated with high viral vector doses, together with safety and immunological concerns. Collectively, the results obtained in the hematological and neuromuscular fields emphasize the transformative impact of CRISPR/Cas9 for patients affected by these debilitating conditions. As each field suffers from different and specific challenges, the clinical translation of CRISPR therapies may progress differentially depending on the genetic disorder. Ongoing investigations and clinical trials will address risks and limitations of these therapies, including long-term efficacy, potential genotoxicity, and adverse immune reactions. This review provides insights into the diverse applications of CRISPR-based technologies in both preclinical and clinical settings for monogenic blood disorders and muscular dystrophy and compare advances in both fields while highlighting current trends, difficulties, and challenges to overcome.

Associations between subjective social status and predictors of interest in genetic testing among women diagnosed with breast cancer at a young age.

Genetic testing for gene mutations which elevate risk for breast cancer is particularly important for women diagnosed at a young age. Differences remain in access and utilization to testing across social groups, and research on the predictors of interest in genetic testing for women diagnosed at a young age is limited. We examined the relationships between subjective social status (SSS) and variables previously identified as possible predictors of genetic testing, including genome sequencing knowledge, genetic worry, cancer worry, health consciousness, decision-making preferences, genetic self-efficacy, genetic-related beliefs, and subjective numeracy, among a cohort of women who were diagnosed with breast cancer at a young age. In this sample (n = 1,076), those who had higher SSS had significantly higher knowledge about the limitations of genome sequencing (Odds Ratio (OR) = 1.11; 95% CI = 1.01-1.21) and significantly higher informational norms (OR = 1.93; 95% CI = 1.19-3.14) than those with lower SSS. Similarly, education (OR = 2.75; 95% CI = 1.79-4.22), health status (OR = 2.18; 95% CI = 1.44-3.31) were significant predictors among higher SSS women compared to lower SSS women in our multivariate analysis. Lower SSS women with low self-reported income (OR = 0.13; 95% CI = 0.08-0.20) had lower odds of genetic testing interest. Our results are consistent with some prior research utilizing proxy indicators for socioeconomic status, but our research adds the importance of using a multidimensional indicator such as SSS to examine cancer and genetic testing predictor outcomes. To develop interventions to improve genetic knowledge, researchers should consider the social status and contexts of women diagnosed with breast cancer at a young age (or before 40 years old) to ensure equity in the distribution of genetic testing benefits.

413 Perceptions and Concerns: Navigating Genetic Research Participation Among At-Risk Individuals for Inherited Conditions

OBJECTIVES/GOALS: Motivations and hesitations about participating in genetic research among those at risk of inherited conditions are unclear. We aim to understand perceptions, perspectives, and concerns of these individuals regarding genetic research studies, especially for hard-to-diagnose diseases. METHODS/STUDY POPULATION: Mix method study of 150 Hispanics individuals in Puerto Rico (PR) at risk for in heriting a condition. These individuals, with limited diagnostic data, are attending genetics clinics or invited to a genetics study at the University of Puerto Rico Medical Sciences Campus. Structured surveys and interviews will be conducted. Surveys will gauge general perceptions and feelings toward genetic research, while interviews will provide a deeper understanding of participants’ personal narratives and experiences. All sessions will be recorded, transcribed, and analyzed using NVivo qualitative analysis software. Thematic analysis will be employed to identify recurring themes and sentiments. RESULTS/ANTICIPATED RESULTS: Weanticipatevaried responses: some enthusiastic about genetic research benefits, others having reservations due to privacy, cultural beliefs, or past experiences. A significant portion may express concerns about genetic research’s impact on insurance and potential discrimination. We also expect to uncover systemic challenges that hinder participation among Hispanics living in PR, such as a lack of information or misconceptions about genetic research. This study will overview factors, both encouraging and inhibitory, influencing decisions to join genetic research. Quantitative genetic literacy survey data will undergo descriptive analysis and multivariate logistic regression. DISCUSSION/SIGNIFICANCE: Hispanics in PR exhibit a rich tapestry of genetic variations being a focal point for genetic research. Understanding perceptions is vital among those at risk for inherited conditions. Insights can shape outreach and education strategies, ensuring participants are informed, concerns met, and empowered to make decisions alignined their views.

Parental kinship coefficient but not paternal coloration predicts early offspring growth in lake char

The ‘good genes’ hypotheses of sexual selection predict that females prefer males with strong ornaments because they are in good health and vigor and can afford the costs of the ornaments. A key assumption of this concept is that male health and vigor are useful predictors of genetic quality and hence offspring performance. We tested this prediction in wild-caught lake char (Salvelinus umbla) whose breeding coloration is known to reveal aspects of male health. We first reanalyzed results from sperm competition trials in which embryos of known parenthood had been raised singly in either a stress- or non-stress environment. Paternal coloration did not correlate with any measures of offspring performance. However, offspring growth was reduced with higher kinship coefficients between the parents. To test the robustness of these first observations, we collected a new sample of wild males and females, used their gametes in a full-factorial in vitro breeding experiment, and singly raised about 3000 embryos in either a stress- or non-stress environment (stress induced by microbes). Again, paternal coloration did not predict offspring performance, while offspring growth was reduced with higher kinship between the parents. We conclude that, in lake char, the genetic benefits of mate choice would be strongest if females could recognize and avoid genetically related males, while male breeding colors may be more relevant in intra-sexual selection.

Mitochondrial function and sexual selection: can physiology resolve the 'lek paradox'?

Across many taxa, males use elaborate ornaments or complex displays to attract potential mates. Such sexually selected traits are thought to signal important aspects of male 'quality'. Female mating preferences based on sexual traits are thought to have evolved because choosy females gain direct benefits that enhance their lifetime reproductive success (e.g. greater access to food) and/or indirect benefits because high-quality males contribute genes that increase offspring fitness. However, it is difficult to explain the persistence of female preferences when males only provide genetic benefits, because female preferences should erode the heritable genetic variation in fitness that sexually selected traits signal. This 'paradox of the lek' has puzzled evolutionary biologists for decades, and inspired many hypotheses to explain how heritable variation in sexually selected traits is maintained. Here, we discuss how factors that affect mitochondrial function can maintain variation in sexually selected traits despite strong female preferences. We discuss how mitochondrial function can influence the expression of sexually selected traits, and we describe empirical studies that link the expression of sexually selected traits to mitochondrial function. We explain how mothers can affect mitochondrial function in their offspring by (a) influencing their developmental environment through maternal effects and (b) choosing a mate to increase the compatibility of mitochondrial and nuclear genes (i.e. the 'mitonuclear compatibility model of sexual selection'). Finally, we discuss how incorporating mitochondrial function into models of sexual selection might help to resolve the paradox of the lek, and we suggest avenues for future research.

Genetic benefits of female from extra-pair paternity are context dependent within the socially monogamous Tree Sparrow

Females actively seek extra-pair paternity (EPP) to acquire a fitness advantage for their offspring. The “context-dependence hypothesis” posits that female extra-pair mate choice has plasticity in response to environmental conditions, and therefore magnitude of female genetic benefits from EPP depends on the environmental variation. Furthermore, chronic heavy metal pollution can cause adverse effects on fitness-related traits of wild birds. However, few studies were available on the interactions between heavy metal pollution and EPP. We selected an area that was contaminated by heavy metals for more than 60 years (Baiyin, BY), a relatively unpolluted area (Liujiaxia, LJX), and Tree Sparrows (Passer montanus) as study species to explore the response of female extra-pair mate choice and genetic benefits from EPP to heavy metal pollution in socially monogamous birds. The relatedness between social mates and extra-pair mates was investigated. Additionally, we compared the body size and heterozygosity of extra-pair offspring (EPO), within-pair offspring (WPO), social males and extra-pair males from the two Tree Sparrow populations. We found that at BY, female Tree Sparrows tended to choose extra-pair males with larger body size and lower genetic similarity, thereby producing higher heterozygosity and larger body size of EPO compared with those of WPO. However, no similar phenomenon was observed in the Tree Sparrow population from LJX. In addition, there was a significant interaction between population and paternity in the analyses of the fitness-related traits, suggesting that environmental variation could affect female genetic benefits from EPP. This study confirmed the existence of presumed interactions between environmental pollution and EPP within the natural population of socially monogamous Tree Sparrows. Our findings shed lights on the possible effects of long-term environmental stress on mating system in wild birds.

Neutrosophic Sets in Investigating the Right to Genetic Information: A Study using Fuzzy Cognitive Maps and D-OWA

This article provides a comprehensive view of the evolution and ethical implications of genetics, from its historical origins to modern advancements like the Human Genome Project. It emphasizes the importance of genetic information in disease prediction and understanding human diversity while highlighting the need to address associated ethical and privacy issues. It introduces Fuzzy Cognitive Maps (FCM) and the Dependent OWA (D-OWA) aggregation operator as innovative tools for analyzing the complex landscape of the Right to Genetic Information (RGI) in an international context, identifying key factors such as legal frameworks, technological advancements, access to health, culture, ethics, and commercial interests. The research reveals that while legal framework and technology are predominant, other factors also play significant roles in managing RGI. The application of D-OWA provides additional insights, confirming that conventional centrality assessments adequately reflect the priorities and influence of factors in RGI. It concludes by underlining the need for specific strategies to address these challenges, such as strengthening the legal framework, promoting ethics in genetics, improving public education, and respecting cultural diversity, to protect individual rights while leveraging the benefits of genetics for society.

The genetic legacy of the first successful reintroduction of a mammal to Britain: Founder events and attempted genetic rescue in Scotland's beaver population.

Conservation translocations often inherently involve a risk of genetic diversity loss, and thus loss of adaptive potential, but this risk is rarely quantified or monitored through time. The reintroduction of beavers to Scotland, via the Scottish Beaver Trial in Knapdale, is an example of a translocation that took place in the absence of genetic data for the founder individuals and resulted in a small and suspected to be genetically depauperate population. In this study we use a high-density SNP panel to assess the genetic impact of that initial translocation and the effect of subsequent reinforcement translocations using animals from a different genetic source to the original founders. We demonstrate that the initial translocation did, indeed, lead to low genetic diversity (H o = 0.052) and high mean kinship (KING-robust = 0.159) in the Knapdale population compared to other beaver populations. We also show that the reinforcement translocations have succeeded in increasing genetic diversity (H o = 0.196) and reducing kinship (KING robust = 0.028) in Knapdale. As yet, there is no evidence of admixture between the two genetic lineages that are now present in Knapdale and such admixture is necessary to realise the full genetic benefits of the reinforcement and for genetic reinforcement and then rescue to occur; future genetic monitoring will be required to assess whether this has happened. We note that, should admixture occur, the Knapdale population will harbour combinations of genetic diversity not currently seen elsewhere in Eurasian beavers, posing important considerations for the future management of this population. We consider our results in the wider context of beaver conservation throughout Scotland and the rest of Britain, and advocate for more proactive genetic sampling of all founders to allow the full integration of genetic data into translocation planning in general.

Maternal exercise during pregnancy modulates genotoxicity caused by high fructose consumption in mice offspring.

Pregnancy is a period that is characterized by several metabolic and physiological changes and requires special attention, especially with regard to the relationship between feeding and foetal development. Therefore, the objective of this study was to evaluate whether the practice of voluntary physical exercise (VPE) in combination with chronic consumption of fructose (FRU) from the beginning of life and/or until the gestational period causes genotoxic changes in pregnant females and in their offspring. Seventy Swiss female mice received FRU in the hydration bottle and/or practiced VPE for 8 weeks (prepregnancy/pregnancy). After the lactation period, the offspring groups were separated by sex. It was observed that the consumption of FRU affected the food consumption, serum concentration of FRU, and glycemic profile in the mothers and that the VPE decreases these parameters. In addition, FRU was genotoxic in the mothers' peripheral tissues and VPE had a preventive effect on these parameters. The offspring showed changes in food consumption, serum FRU concentration, and body weight, in addition to an increase in the adiposity index in male offspring in the FRU (FRU) group and a decrease in the FRU + VPE group. FRU leads to hepatic steatosis in the offspring and VPE was able to decrease the area of steatosis. In addition, FRU led to genotoxicity in the offspring and VPE was able to modulate this effect, reducing damages. In conclusion, we observed that all interventions with VPE had nutritional, genetic, and biochemical benefits of the mother and her offspring.

Research Note: Injection of adenoviral CRISPR/Cas9 system targeting melanophilin gene into different sites of embryos induced regional feather color changes in posthatch quail

Poultry species is an important animal model in both avian research and the poultry industry. To advance our understanding of genetic factors and benefit both fields, a gene of interest can be genetically edited, and consequential phenotypic changes can be investigated. Injection of adenovirus containing the CRISPR/Cas9 system into avian blastoderm induced genome editing in blastodermal cells randomly, including primordial germ cells, which results in generation of whole-body knockout in the offspring of the virus-injected quail. However, to observe phenotypic and functional changes in whole-body, homozygous knockout of genes using this genome editing technology requires at least 2 generations of breeding of chimeric, and heterozygotes birds. In the current study, we developed a strategy to investigate the gene function in 1-generation by inducing regional genome editing around the injection sites with CRISPR/Cas9 adenovirus. The adenoviral CRISPR/Cas9 vector targeting the melanophilin (Mlph) gene, regulating feather pigmentation, was injected into 2 different regions of embryos, the cervical flexure of quail embryos at HH stage 13 to 15 and the tip of the upper limb bud of embryos at HH stage 22 to 24, to induce genome editing in those regions. Indel mutations in the target loci of the Mlph gene were detected by extracting genomic DNA from the embryonic tissues, and consequential phenotypes, feather color changes, were analyzed at 1 mo after hatch. Injection of the adenovirus into the cervical flexure and the tip of the upper limb bud of embryos resulted in 8 to 21% efficiency of indel mutation in the embryonic cells of the injected regions. In the posthatch quail, gray feathers were shown on their upper back and primary wing feathers, corresponding to the injection sites at embryos. Successful validation of this strategy for inducing genome editing in parts of tissues within 1-generation will accelerate studies on genetic functions with advantages of less time and cost, facilitating avian research and providing foundations for future application for the poultry industry.

Cathepsin S activity controls chronic stress-induced muscle atrophy and dysfunction in mice

Exposure to chronic psychological stress (CPS) is an intractable risk factor for inflammatory and metabolic diseases. Lysosomal cysteinyl cathepsins play an important role in human pathobiology. Given that cathepsin S (CTSS) is upregulated in the stressed vascular and adipose tissues, we investigated whether CTSS participates in chronic stress-induced skeletal muscle mass loss and dysfunction, with a special focus on muscle protein metabolic imbalance and apoptosis. Eight-week-old male wildtype (CTSS+/+) and CTSS-knockout (CTSS−/−) mice were randomly assigned to non-stress and variable-stress groups. CTSS+/+ stressed mice showed significant losses of muscle mass, dysfunction, and fiber area, plus significant mitochondrial damage. In this setting, stressed muscle in CTSS+/+ mice presented harmful alterations in the levels of insulin receptor substrate 2 protein content (IRS-2), phospho-phosphatidylinositol 3-kinase, phospho-protein kinase B, and phospho-mammalian target of rapamycin, forkhead box-1, muscle RING-finger protein-1 protein, mitochondrial biogenesis-related peroxisome proliferator-activated receptor-γ coactivator-α, and apoptosis-related B-cell lymphoma 2 and cleaved caspase-3; these alterations were prevented by CTSS deletion. Pharmacological CTSS inhibition mimics its genetic deficiency-mediated muscle benefits. In C2C12 cells, CTSS silencing prevented stressed serum- and oxidative stress-induced IRS-2 protein reduction, loss of the myotube myosin heavy chain content, and apoptosis accompanied by a rectification of investigated molecular harmful changes; these changes were accelerated by CTSS overexpression. These findings demonstrated that CTSS plays a role in IRS-2-related protein anabolism and catabolism and cell apoptosis in stress-induced muscle wasting, suggesting a novel therapeutic strategy for the control of chronic stress-related muscle disease in mice under our experimental conditions by regulating CTSS activity.

Neuromuscular disease genetics in under-represented populations: increasing data diversity.

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses 'solved' or 'possibly solved' ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% 'solved' and ∼13% 'possibly solved' outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally.

The quest for good genes: Epigamic traits, fitness, MHC and multilocus heterozygosity in the guppy.

The 'good genes' hypothesis for the evolution of male secondary sexual traits poses that female preferences for such traits are driven by indirect genetic benefits. However, support for the hypothesis remains ambiguous, and, in particular, the genetic basis for the benefits has rarely been investigated. Here, we use seminatural populations of Trinidadian guppies to investigate whether sexually selected traits (orange, black and iridescent colouration, gonopodium length and body size) predict fitness measured as the number of grandoffspring, a metric that integrates across fitness components and sexes. Furthermore, we tested whether two potential sources of genetic benefits-major histocompatibility complex (MHC) genotypes and multilocus heterozygosity (MLH)-are significant predictors of fitness and of the size of sexually selected traits. We found a significant, nonlinear effect of the area of black pigmentation and male body size on the number of grandoffspring, suggesting stabilizing selection on black area, and nonlinear selection favouring small body size. MLH was heritable (h2 = 0.14) and significantly predicted the number of grandoffspring, indicating the potential for genetic benefits based on heterozygosity. We also found support for local heterozygosity effects, which may reflect a noneven distribution of genetic load across the genome. MHC genotype was not significantly associated with any tested fitness component, or with the load of Gyrodactylus parasites. Neither MHC nor MLH was significant predictor of sexually selected traits. Overall, our results highlight the role of heterozygosity in determining fitness, but do not provide support for male sexually selected traits being indicators of genetic quality.

Origin, domestication, taxonomy, botanical description, genetics and cytogenetics, genetc diversity and breeding of chickpea (Cicer arietinum L.)

The chickpea or chick pea (Cicer arietinum) is an annual legume of the family Fabaceae, subfamily Faboideae. Its different types are variously known as gram or Bengal gram, chhana, chana, or channa, garbanzo or garbanzo bean, or Egyptian pea. Also known as ceci beans, Indian peas, kadale kaalu, sanaga pappu, and shimbra. The Sanskrit name for chickpea is chennuka, and hence, the name chana in the Sanskrit-derived languages such as Hindi. Chickpea is a cool season legume crop grown world- wide as a food crop. The seed is the main edible part of the plant. Chickpea is a cheap and important source of protein for those people who cannot afford animal protein or who are largely vegetarian. Furthermore, chickpea is also a good source of minerals (calcium, phosphorus, magnesium, zinc and iron), unsaturated fatty acids, fibre and β-carotene). Chickpea also plays an important role in maintaining soil fertility by fixing nitrogen at rates of up to 140 kg/ha/year. Therefore, this crop requires relatively low inputs of nitrogen as it derives 70% of its N through symbiotic N2 fixation and benefits other cereal crops as well. On the basis of seed colour and geographical distribution, chickpea is grouped into two types: desi (Indian origin) and kabuli (Mediterranean and Middle Eastern origin). Desi seeds are brown, black or green in colour and are cultivated as a legume crop. Kabuli seeds are white to cream coloured and are used for cooking purposes for humans. The seed weight generally ranges from 0.1 to 0.3 g for desi and 0.2 to 0.6 g for kabuli/. The desi type accounts for about 80–85% of total chickpea production, and is grown mostly in Asia and Africa, while the kabuli types are largely grown in West Asia, North Africa, North America and Europe. Chickpeas appear in early recordings in Turkey about 3500 BCE and in France 6790 BCE. India produces the most chickpeas worldwide but they are grown in more than 50 countries. An excellent source of carbohydrate, protein, fiber, B vitamins, and some minerals, they are a nutritious staple of many diets. Chickpea is widely grown for its nutritious seeds. Chickpeas are an important food plant in India, Africa, and Central and South America. The seeds are high in fibre and protein and are a good source of iron, phosphorus, and folic acid. As with other legumes, chickpeas have a symbiotic association with nitrogen-fixing bacteria and can be rotated with nitrogen-intensive crops such as cereals to improve soil conditions. Till 17th century, roasted and grounded chickpeas and were brewed as a substitute for a coffee in Europe. Around 800 AD, chickpeas were associated with Venus, the Roman Goddess for beauty and love as it improves fertility by increasing sperm production, stimulating menstruation and lactation. In this review article on Origin, Domestication, Taxonomy, Botanical Description, Genetics and Cytogenetics, Genetic Diversity, Breeding, Uses, Nutritional Value and Health Benefits of Chickpea are discussed.

Transgenerational effects of multiple mating in Spodoptera litura Fabricius (Lepidoptera: Noctuidae).

Polyandrous mating can result in sexual conflict and/or promote the evolution of mating patterns. Does multiple mating by females support the genetic benefits hypothesis and can it be validated as an evolutionary strategy? If we are to decipher the consequences of sexual interactions and understand the interplay of sexual conflict and multiple generational benefits, the transgenerational effects need to be followed over multiple generations. We investigated the effects of three mating patterns, single mating, repeated mating, and multiple mating, on parental Spodoptera litura copulation behavior, and then identified the impact on the development, survival, and fecundity of the F1 and F2 generations. Fecundity was not significantly affected in the F1 generation but was substantially enhanced in the F2 generation. There was a reversal of offspring fitness across the F2 generations from the F1 generations in progeny produced by multiple mating. In addition, the intrinsic rate of increase, finite rate of increase and net reproductive rate in the F1 generation the multiple mating treatment was significantly lower than in the single mating treatment, but there was no apparent effect on the F2 generation. Repeated mating had no significant effects on progeny fitness. We postulate that multiple mating imposes cross-transgenerational effects and may ultimately influence multigenerational fitness in S. litura.