Circadian clock gene polymorphisms implicated in human pathologies.

Circadian rhythms, ~24 h cycles of physiological and behavioral processes, can be synchronized by external signals (e.g., light) and persist even in their absence. Consequently, dysregulation of circadian rhythms adversely affects the well-being of the organism. This timekeeping system is generated and sustained by a genetically encoded endogenous mechanism composed of interlocking transcriptional/translational feedback loops that generate rhythmic expression of core clock genes. Genome-wide association studies (GWAS) and forward genetic studies show that SNPs in clock genes influence gene regulation and correlate with the risk of developing various conditions. We discuss genetic variations in core clock genes that are associated with various phenotypes, their implications for human health, and stress the need for thorough studies in this domain of circadian regulation.

Splicing-specific transcriptome-wide association uncovers genetic mechanisms for schizophrenia.

Recent studies have highlighted the essential role of RNA splicing, a key mechanism of alternative RNA processing, in establishing connections between genetic variations and disease. Genetic loci influencing RNA splicing variations show considerable influence on complex traits, possibly surpassing those affecting total gene expression. Dysregulated RNA splicing has emerged as a major potential contributor to neurological and psychiatric disorders, likely due to the exceptionally high prevalence of alternatively spliced genes in the human brain. Nevertheless, establishing direct associations between genetically altered splicing and complex traits has remained an enduring challenge. We introduce Spliced-Transcriptome-Wide Associations (SpliTWAS) to integrate alternative splicing information with genome-wide association studies to pinpoint genes linked to traits through exon splicing events. We applied SpliTWAS to two schizophrenia (SCZ) RNA-sequencing datasets, BrainGVEX and CommonMind, revealing 137 and 88 trait-associated exons (in 84 and 67 genes), respectively. Enriched biological functions in the associated gene sets converged on neuronal function and development, immune cell activation, and cellular transport, which are highly relevant to SCZ. SpliTWAS variants impacted RNA-binding protein binding sites, revealing potential disruption of RNA-protein interactions affecting splicing. We extended the probabilistic fine-mapping method FOCUS to the exon level, identifying 36 genes and 48 exons as putatively causal for SCZ. We highlight VPS45 and APOPT1, where splicing of specific exons was associated with disease risk, eluding detection by conventional gene expression analysis. Collectively, this study supports the substantial role of alternative splicing in shaping the genetic basis of SCZ, providing a valuable approach for future investigations in this area.

A perspective on genetic and polygenic risk scores-advances and limitations and overview of associated tools.

Polygenetic Risk Scores are used to evaluate an individual's vulnerability to developing specific diseases or conditions based on their genetic composition, by taking into account numerous genetic variations. This article provides an overview of the concept of Polygenic Risk Scores (PRS). We elucidate the historical advancements of PRS, their advantages and shortcomings in comparison with other predictive methods, and discuss their conceptual limitations in light of the complexity of biological systems. Furthermore, we provide a survey of published tools for computing PRS and associated resources. The various tools and software packages are categorized based on their technical utility for users or prospective developers. Understanding the array of available tools and their limitations is crucial for accurately assessing and predicting disease risks, facilitating early interventions, and guiding personalized healthcare decisions. Additionally, we also identify potential new avenues for future bioinformatic analyzes and advancements related to PRS.

Phylogenetic analysis and antigenic epitope prediction for E6 and E7 of Alpha-papillomavirus 9 in Taizhou, China.

BACKGROUND: Alpha-papillomavirus 9 (α-9) is a member of the human papillomavirus (HPV) α genus, causing 75% invasive cervical cancers worldwide. The purpose of this study was to provide data for effective treatment of HPV-induced cervical lesions in Taizhou by analysing the genetic variation and antigenic epitopes of α-9 HPV E6 and E7. METHODS: Cervical exfoliated cells were collected for HPV genotyping. Positive samples of the α-9 HPV single type were selected for E6 and E7 gene sequencing. The obtained nucleotide sequences were translated into amino acid sequences (protein primary structure) using MEGA X, and positive selection sites of the amino acid sequences were evaluated using PAML. The secondary and tertiary structures of the E6 and E7 proteins were predicted using PSIPred, SWISS-MODEL, and PyMol. Potential T/B-cell epitopes were predicted by Industrial Engineering Database (IEDB). RESULTS: From 2012 to 2023, α-9 HPV accounted for 75.0% (7815/10423) of high-risk HPV-positive samples in Taizhou, both alone and in combination with other types. Among these, single-type-positive samples of α-9 HPV were selected, and the entire E6 and E7 genes were sequenced, including 298 HPV16, 149 HPV31, 185 HPV33, 123 HPV35, 325 HPV52, and 199 HPV58 samples. Compared with reference sequences, 34, 12, 10, 2, 17, and 17 nonsynonymous nucleotide mutations were detected in HPV16, 31, 33, 35, 52, and 58, respectively. Among all nonsynonymous nucleotide mutations, 19 positive selection sites were selected, which may have evolutionary significance in rendering α-9 HPV adaptive to its environment. Immunoinformatics predicted 57 potential linear and 59 conformational B-cell epitopes, many of which are also predicted as CTL epitopes. CONCLUSION: The present study provides almost comprehensive data on the genetic variations, phylogenetics, positive selection sites, and antigenic epitopes of α-9 HPV E6 and E7 in Taizhou, China, which will be helpful for local HPV therapeutic vaccine development.

Comparative Phylogenetic Analysis of Ancient Korean Tea "Hadong Cheon-Nyeon Cha (Camellia sinensis var. sinensis)" Using Complete Chloroplast Genome Sequences.

Wild teas are valuable genetic resources for studying evolution and breeding. Here, we report the complete chloroplast genome of the ancient Korean tea 'Hadong Cheon-nyeon Cha' (C. sinensis var. sinensis), which is known as the oldest tea tree in Korea. This study determined seven Camellia sinensis var. sinenesis, including Hadong Cheon-nyeon Cha (HCNC) chloroplast genome sequences, using Illumina sequencing technology via de novo assembly. The chloroplast genome sizes ranged from 157,019 to 157,114 bp and were organized into quadripartite regions with the typical chloroplast genomes. Further, differences in SNPs and InDels were detected across the seven chloroplast genomes through variance analysis. Principal component and phylogenetic analysis suggested that regional constraints, rather than functional constraints, strongly affected the sequence evolution of the cp genomes in this study. These genomic resources provide evolutionary insight into Korean tea plant cultivars and lay the foundation for a better understanding of the ancient Korean tea plant HCNC.

Productive Poplar Genotypes Exhibited Temporally Stable Low Stem Embolism Resistance and Hydraulic Resistance Segmentation at the Stem-Leaf Transition.

Breeding tree genotypes that are both productive and drought-resistant is a primary goal in forestry. However, the relationships between plant hydraulics and yield at the genotype level, and their temporal stabilities, remain unclear. We selected six poplar genotypes from I-101 (Populus alba) × 84 K (P. alba × Popolus tremula var. glandulosa) for experiments in the first and fourth years after planting in a common garden. Measurements included stem embolism resistance, shoot hydraulic resistance and its partitioning between stems and leaves, vessel- and pit-level anatomy, leaf carbon acquisition capacity, carbon allocation to leaves, and aboveground biomass (yield proxy). Significant genetic variations in hydraulic properties and yield were found among genotypes in both years. Productive genotypes had wide vessels, large thin pit membranes, small pit apertures, and shallow pit chambers. Hydraulic resistance was negatively correlated with yield, enabling high stomatal conductance and assimilation rates. Productive genotypes allocated less aboveground carbon and hydraulic resistance to leaves. Temporally stable trade-offs between stem embolism resistance and yield, and between hydraulic segmentation and yield, were identified. These findings highlight the tight link between hydraulic function and yield and suggest that stable trade-offs may challenge breeding poplar genotypes that are both productive and drought-resistant.

Association between genetic variants of transmembrane transporters and susceptibility to anthracycline-induced cardiotoxicity: Current understanding and existing evidence.

Anthracyclines remain the cornerstone of numerous chemotherapeutic protocols, with beneficial effects against haematological malignancies and solid tumours. Unfortunately, the clinical usefulness of anthracyclines is compromised by the development of cardiotoxic side effects, leading to dose limitations or treatment discontinuation. There is no absolute linear correlation between the incidence of cardiotoxicity and the threshold dose, suggesting that genetic factors may modify the association between anthracyclines and cardiotoxicity risk. And the majority of single nucleotide polymorphisms (SNPs) associated with anthracycline pharmacogenomics were identified in the ATP-binding cassette (ABC) and solute carrier (SLC) transporters, generating increasing interest in the pharmacogenetic implications of their genetic variations for anthracycline-induced cardiotoxicity (AIC). This review focuses on the influence of SLC and ABC polymorphisms on AIC and highlights the prospects and clinical significance of pharmacogenetics for individualised preventive approaches.

Sex affects immune response capacity against COVID-19 infection.

The genetic variability of each individual may lead to the identification of completely different genetic polymorphisms which are associated with a different sensitivity to infectious diseases in humans. Such genetic variability allows the immune system to respond differently to viral agents, therefore only a fraction of humans develop severe symptoms, as happened with SARS-CoV-2. Such knowledge is critical to enable the development of appropriate pharmacological solutions to prevent the consequences of insufficient immunity in dealing with serious viral diseases such as SARS-CoV-2. For instance, global epidemiological data show that male sex is a risk factor for the severe evolution of SARS-CoV-2 disease. Men, due to higher production of Testosterone (TLT), are more vulnerable than females. Women, due to greater expression of the TLR7 gene found on the X chromosome, a key innate immunity gene that encodes Toll-like proteins, are able to synthesise more antiviral proteins and interferons in dendritic cells, resulting in a more robust immune system capable of preventing severe SARS-CoV-2 viral disease. This manuscript highlights how human genetic variability can lead to severe infectious symptoms in some individuals who must take appropriate prophylactic actions, such as vaccination, to prevent this.

Genes Selectively Expressed in Rat Organs.

Background: Understanding organic functions at a molecular level is important for scientists to unveil the disease mechanism and to develop diagnostic or therapeutic methods. Aims: The present study tried to find genes selectively expressed in 11 rat organs, including the adrenal gland, brain, colon, duodenum, heart, ileum, kidney, liver, lung, spleen, and stomach. Materials and Methods: Three normal male Sprague-Dawley (SD) rats were anesthetized, their organs mentioned above were harvested, and RNA in the fresh organs was extracted. Purified RNA was reversely transcribed and sequenced using the Solexa high-throughput sequencing technique. The abundance of a gene was measured by the expected value of fragments per kilobase of transcript sequence per million base pairs sequenced (FPKM). Genes in organs with the highest expression level were sought out and compared with their median value in organs. If a gene in the highest expressed organ was significantly different (p < 0.05) from that in the medianly expressed organ, accompanied by q value < 0.05, and accounted for more than 70% of the total abundance, the gene was assumed as the selective gene in the organ. Results & Discussion: The Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) pathways were enriched by the highest expressed genes. Based on the criterion, 1,406 selective genes were screened out, 1,283 of which were described in the gene bank and 123 of which were waiting to be described. KEGG and GO pathways in the organs were partly confirmed by the known understandings and a good portion of the pathways needed further investigation. Conclusion: The novel selective genes and organic functional pathways are useful for scientists to unveil the mechanisms of the organs at the molecular level, and the selective genes' products are candidate disease markers for organs.

Genome-wide identification of m6A-related gene family and the involvement of TdFIP37 in salt stress in wild emmer wheat.

KEY MESSAGE: The genomic organization, phylogenetic relationship, expression patterns, and genetic variations of m6A-related genes were systematically investigated in wild emmer wheat and the function of TdFIP37 regulating salt tolerance was preliminarily determined. m6A modification is one of the most abundant and crucial RNA modifications in eukaryotics, playing the indispensable role in growth and development as well as stress response in plants. However, its significance in wild emmer wheat remains elusive. Here, a genome-wide search of m6A-related genes was conducted in wild emmer wheat to obtain 64 candidates, including 21 writers, 17 erasers, and 26 readers. Phylogenetic and collinearity analysis demonstrated that segmental duplication and polyploidization contributed mainly to the expansion of m6A-related genes in wild emmer. A number of cis-acting elements involving in stress and hormonal regulation were found in the promoter regions of them, such as MBS, LTR, and ABRE. Genetic variation of them was also investigated using resequencing data and obvious genetic bottleneck was occurred on them during wild emmer wheat domestication process. Furthermore, the salt-responsive candidates were investigated through RNA-seq data and qRT-PCR validation using the salt-tolerant and -sensitive genotypes and the co-expression analysis showed that they played the hub role in regulating salt stress response. Finally, the loss-function mutant of Tdfip37 displayed the significantly higher salt-sensitive compared to WT and then RNA-seq analysis demonstrated that FIP37 mediated the MAPK pathway, hormone signal transduction, as well as transcription factor to regulate salt tolerance. This study provided the potential m6A genes for functional analysis, which will contribute to better understand the regulatory roles of m6A modification and also improve the salt tolerance from the perspective of epigenetic approach in emmer wheat and other crops.

Changing and Evolution of Influenza Virus: Is It a Trivial Flu?

BACKGROUND: Influenza viruses are etiological agents which cause contagious respiratory, seasonal epidemics and, for influenza A subtypes, pandemics. The clinical picture of influenza has undergone continuous change over the years, due to intrinsic viral evolution as well as "reassortment" of its genomic segments. The history of influenza highlights its ability to adapt and to rapidly evolve, without specific circumstances. This reflects the complexity of this pathology and poses the fundamental question about its assumption as a "common illness" and its impact on public health. SUMMARY: The global influenza epidemics and pandemics claimed millions of deaths, leaving an indelible mark on public health and showing the need for a better comprehension of the influenza virus. The clear understanding of genetic variations during the influenza seasonal epidemics is a crucial point for developing effective strategies for prevention, treatment, and vaccine design. The recent advance in next-generation sequencing approaches, model systems to virus culture, and bioinformatics pipeline played a key role in the rapid characterization of circulating influenza strains. In particular, the increase in computational power allowed the performance of complex tasks in healthcare settings through machine learning algorithms, which analyze different variables, such as medical and laboratory outputs, to optimize medical research and improve public health systems. The early detection of emerging and reemerging pathogens is a matter of importance to prevent future pandemics. KEY MESSAGES: The perception of influenza as a "trivial flu" or a more serious public health concern is a subject of ongoing debate, reflecting the multifaceted nature of this infectious disease. The variability in the severity of influenza sheds light on the unpredictability of the viral characteristics, coupled with the challenges in accurately predicting circulating strains. This adds complexity to the public health burden of influenza and highlights the need for targeted interventions.

G-quadruplex structural variations in human genome associated with single-nucleotide variations and their impact on gene activity.

G-quadruplexes (G4s) formed by guanine-rich nucleic acids play a role in essential biological processes such as transcription and replication. Besides the >1.5 million putative G-4-forming sequences (PQSs), the human genome features >640 million single-nucleotide variations (SNVs), the most common type of genetic variation among people or populations. An SNV may alter a G4 structure when it falls within a PQS motif. To date, genome-wide PQS-SNV interactions and their impact have not been investigated. Herein, we present a study on the PQS-SNV interactions and the impact they can bring to G4 structures and, subsequently, gene expressions. Based on build 154 of the Single Nucleotide Polymorphism Database (dbSNP), we identified 5 million gains/losses or structural conversions of G4s that can be caused by the SNVs. Of these G4 variations (G4Vs), 3.4 million are within genes, resulting in an average load of >120 G4Vs per gene, preferentially enriched near the transcription start site. Moreover, >80% of the G4Vs overlap with transcription factor-binding sites and >14% with enhancers, giving an average load of 3 and 7.5 for the two regulatory elements, respectively. Our experiments show that such G4Vs can significantly influence the expression of their host genes. These results reveal genome-wide G4Vs and their impact on gene activity, emphasizing an understanding of genetic variation, from a structural perspective, of their physiological function and pathological implications. The G4Vs may also provide a unique category of drug targets for individualized therapeutics, health risk assessment, and drug development.

Genomic and Epigenomic Changes in the Progeny of Cold-Stressed Arabidopsis thaliana Plants.

Plants are continuously exposed to various environmental stresses. Because they can not escape stress, they have to develop mechanisms of remembering stress exposures somatically and passing it to the progeny. We studied the Arabidopsis thaliana ecotype Columbia plants exposed to cold stress for 25 continuous generations. Our study revealed that multigenerational exposure to cold stress resulted in the changes in the genome and epigenome (DNA methylation) across generations. Main changes in the progeny were due to the high frequency of genetic mutations rather than epigenetic changes; the difference was primarily in single nucleotide substitutions and deletions. The progeny of cold-stressed plants exhibited the higher rate of missense non-synonymous mutations as compared to the progeny of control plants. At the same time, epigenetic changes were more common in the CHG (C = cytosine, H = cytosine, adenine or thymine, G = guanine) and CHH contexts and favored hypomethylation. There was an increase in the frequency of C to T (thymine) transitions at the CHH positions in the progeny of cold stressed plants; because this type of mutations is often due to the deamination of the methylated cytosines, it can be hypothesized that environment-induced changes in methylation contribute to mutagenesis and may be to microevolution processes and that RNA-dependent DNA methylation plays a crucial role. Our work supports the existence of heritable stress response in plants and demonstrates that genetic changes prevail.

Sanger Sequencing Reveals Novel Variants in GLO-1, ACE, and CBR1 Genes in Patients of Early and Severe Diabetic Nephropathy.

Background and Objectives: Diabetes is a global health issue, with approximately 50% of patients developing diabetic nephropathy (DN) and 25% experiencing early and severe forms of the disease. The genetic factors contributing to rapid disease progression in a subset of these patients are unclear. This study investigates genetic variations in the GLO-1, CBR-1, and ACE genes associated with early and severe DN. Materials and Methods: Sanger DNA sequencing of the exons of CBR1, GLO1, and ACE genes was conducted in 113 patients with early and severe DN (defined as occurring within 10 years of the diagnosis of diabetes and with eGFR < 45 mL/min/1.73 m2) and 100 controls. The impact of identified genetic variations was analyzed using computational protein models created in silico with SWISS-Model and SWISS-Dock for ligand binding interactions. Results: In GLO1, two heterozygous missense mutations, c.102G>T and c.147C>G, and one heterozygous nonsense mutation, c.148G>T, were identified in patients. The SNP rs1049346 (G>A) at location 6:38703061 (GRCh38) was clinically significant. The c.147C>G mutation (C19S) was associated with ligand binding disruption in the GLO1 protein, while the nonsense mutation resulted in a truncated, non-functional protein. In CBR1, two heterozygous variations, one missense c.358G>A, and one silent mutation c.311G>C were observed, with the former (D120N) affecting the active site. No significant changes were noted in ACE gene variants concerning protein structure or function. Conclusions: The study identifies four novel and five recurrent mutations/polymorphisms in GLO1, ACE, and CBR1 genes associated with severe DN in Pakistani patients. Notably, a nonsense mutation in GLO1 led to a truncated, non-functional protein, while missense mutations in GLO1 and CBR1 potentially disrupt enzyme function, possibly accelerating DN progression.

[The pharmacogenetics as integral part of personalized medicine: problems and prospects].

The article considers issues of implementation into clinical practice the principles of 5P medicine in its part of individualization of therapeutic tactics considering genetic characteristics of patients. The analysis of studies concerning influence of allelic variations on metabolism, safety and tolerance of the most often prescribed medicinal preparations was implemented. The main assumptions of pharmacogenomics were considered. Despite broad perspective of applying obtained data in clinical practice, there are a number of unresolved problems related to accessibility of genetic testing to population, ambiguity of approaches to interpretation of obtaining results, ethical issues and legal regulation.

Metabolome genome-wide association study provides biochemical and genetic insights into natural variation of primary metabolites in sesame.

Plants' primary metabolites are of great importance from the survival and nutritional perspectives. However, the genetic bases underlying the profiles of primary metabolites in oilseed crops remain largely unclear. As one of the main oilseed crops, sesame (Sesamum indicum L.) is a potential model plant for investigating oil metabolism in plants. Therefore, the objective of this study is to disclose the genetic variants associated with variation in the content of primary metabolites in sesame. We performed a comprehensive metabolomics analysis of primary metabolites in 412 diverse sesame accessions using gas chromatography-mass spectrometry and identified a total of 45 metabolites, including fatty acids, monoacylglycerols (MAGs), and amino acids. Genome-wide association study unveiled 433 significant single-nucleotide polymorphism loci associated with variation in primary metabolite contents in sesame. By integrating diverse genomic analyses, we identified 10 key candidate causative genes of variation in MAG, fatty acid, asparagine, and sucrose contents. Among them, SiDSEL was significantly associated with multiple traits. SiCAC3 and SiKASI were strongly associated with variation in oleic acid and linoleic acid contents. Overexpression of SiCAC3, SiKASI, SiLTPI.25, and SiLTPI.26 in transgenic Arabidopsis and Saccharomyces cerevisiae revealed that SiCAC3 is a potential target gene for improvement of unsaturated fatty acid levels in crops. Furthermore, we found that it may be possible to breed several quality traits in sesame simultaneously. Our results provide valuable genetic resources for improving sesame seed quality and our understanding of oilseed crops' primary metabolism.

No association of a Vascular endothelial growth factor A (VEGFA) gene polymorphism with pre-eclampsia among pregnant women in Uganda.

BACKGROUND: Vascular endothelial growth factor A (VEGFA) is a major angiogenic factor that plays an important role in the formation of blood vessels during embryonic development. VEGFA has been implicated in the pathophysiology of pre-eclampsia (PE), since pre-eclamptic women present with reduced levels of free circulating VEGFA. The 3' untranslated region (3'-UTR) of the VEGFA gene consists of elements that regulate the transcription and hence expression of the VEGFA protein in circulation. Hence it is suggested that variations thereof could underlie the reduced VEGFA levels observed in pre-eclamptic women. The purpose of this study was to investigate presence of the + 936C/T polymorphism, a common single nucleotide polymorphism (SNP) in the 3'-UTR of the VEGFA gene, and determine its association with PE among pregnant women in Uganda. RESULTS: There was no significant difference observed in the allele and genotype frequencies of the + 936C/T 3' UTR-VEGFA polymorphism between pre-eclamptic and normotensive pregnant women (P > 0.05). Additionally, there was no significant difference in the median plasma levels of free VEGFA among women with the wild type, CT and TT genotypes of the + 936C/T VEGFA polymorphism (median = 0.84 pg/mL (IQR = 0.39-1.41) Vs 1.05 (0.61-1.18) Vs 1.05 (1.05-1.05) respectively, p-value = 0.7161). CONCLUSIONS: These study findings indicate that the + 936C/T 3' UTR-VEGFA polymorphism had no significant association with increased susceptibility to PE among women in Uganda. Further studies with a larger sample size are recommended.

Precision medicine in complex diseases-Molecular subgrouping for improved prediction and treatment stratification.

Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease-both with regards to symptoms and underlying causal mechanisms-and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases-including psychiatric disorders and allergies-available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine.

Genetic control of photoprotection and photosystem II operating efficiency in plants.

Photoprotection against excess light via nonphotochemical quenching (NPQ) is indispensable for plant survival. However, slow NPQ relaxation under low light conditions can decrease yield of field-grown crops up to 40%. Using semi-high-throughput assay, we quantified the kinetics of NPQ and photosystem II operating efficiency (ΦPSII) in a replicated field trial of more than 700 maize (Zea mays) genotypes across 2 yr. Parametrized kinetics data were used to conduct genome-wide association studies. For six candidate genes involved in NPQ and ΦPSII kinetics in maize the loss of function alleles of orthologous genes in Arabidopsis (Arabidopsis thaliana) were characterized: two thioredoxin genes, and genes encoding a transporter in the chloroplast envelope, an initiator of chloroplast movement, a putative regulator of cell elongation and stomatal patterning, and a protein involved in plant energy homeostasis. Since maize and Arabidopsis are distantly related, we propose that genes involved in photoprotection and PSII function are conserved across vascular plants. The genes and naturally occurring functional alleles identified here considerably expand the toolbox to achieving a sustainable increase in crop productivity.

Host genetics and gut microbiota jointly regulate blood biochemical indicators in chickens.

Blood biochemical indicators play a crucial role in assessing an individual's overall health status and metabolic function. In this study, we measured five blood biochemical indicators, including total cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-CH), triglycerides (TG), high-density lipoprotein cholesterol (HDL-CH), and blood glucose (BG), as well as 19 growth traits of 206 male chickens. By integrating host whole-genome information and 16S rRNA sequencing of the duodenum, jejunum, ileum, cecum, and feces microbiota, we assessed the contributions of host genetics and gut microbiota to blood biochemical indicators and their interrelationships. Our results demonstrated significant negative phenotypic and genetic correlations (r = - 0.20 ~ - 0.67) between CHOL and LDL-CH with growth traits such as body weight, abdominal fat content, muscle content, and shin circumference. The results of heritability and microbiability indicated that blood biochemical indicators were jointly regulated by host genetics and gut microbiota. Notably, the heritability of HDL-CH was estimated to be 0.24, while the jejunal microbiability for BG and TG reached 0.45 and 0.23. Furthermore, by conducting genome-wide association study (GWAS) with the single-nucleotide polymorphism (SNPs), insertion/deletion (indels), and structural variation (SV), we identified RAP2C, member of the RAS oncogene family (RAP2C), dedicator of cytokinesis 11 (DOCK11), neurotensin (NTS) and BOP1 ribosomal biogenesis factor (BOP1) as regulators of HDL-CH, and glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5), dihydrodiol dehydrogenase (DHDH), and potassium voltage-gated channel interacting protein 1 (KCNIP1) as candidate genes of BG. Moreover, our findings suggest that cecal RF39 and Clostridia_UCG_014 may be linked to the regulation of CHOL, and jejunal Streptococcaceae may be involved in the regulation of TG. Additionally, microbial GWAS results indicated that the presence of gut microbiota was under host genetic regulation. Our findings provide valuable insights into the complex interaction between host genetics and microbiota in shaping the blood biochemical profile of chickens. KEY POINTS: • Multiple candidate genes were identified for the regulation of CHOL, HDL-CH, and BG. • RF39, Clostridia_UCG_014, and Streptococcaceae were implicated in CHOL and TG modulation. • The composition of gut microbiota is influenced by host genetics.