Identify Candidate Genes Research Articles

Genomic and transcriptomic analyses reveal polygenic architecture for ecologically important traits in aspen (Populustremuloides Michx.).

Intraspecific genetic variation in foundation species such as aspen (Populus tremuloides Michx.) shapes their impact on forest structure and function. Identifying genes underlying ecologically important traits is key to understanding that impact. Previous studies, using single-locus genome-wide association (GWA) analyses to identify candidate genes, have identified fewer genes than anticipated for highly heritable quantitative traits. Mounting evidence suggests that polygenic control of quantitative traits is largely responsible for this "missing heritability" phenomenon. Our research characterized the genetic architecture of 30 ecologically important traits using a common garden of aspen through genomic and transcriptomic analyses. A multilocus association model revealed that most traits displayed a highly polygenic architecture, with most variation explained by loci with small effects (likely below the detection levels of single-locus GWA methods). Consistent with a polygenic architecture, our single-locus GWA analyses found only 38 significant SNPs in 22 genes across 15 traits. Next, we used differential expression analysis on a subset of aspen genets with divergent concentrations of salicinoid phenolic glycosides (key defense traits). This complementary method to traditional GWA discovered 1243 differentially expressed genes for a polygenic trait. Soft clustering analysis revealed three gene clusters (241 candidate genes) involved in secondary metabolite biosynthesis and regulation. Our work reveals that ecologically important traits governing higher-order community- and ecosystem-level attributes of a foundation forest tree species have complex underlying genetic structures and will require methods beyond traditional GWA analyses to unravel.

The Value of Electroretinography in Identifying Candidate Genes for Inherited Retinal Dystrophies: A Diagnostic Guide.

Inherited retinal dystrophies (IRDs) are a group of heterogeneous diseases caused by genetic mutations that specifically affect the function of the rod, cone, or bipolar cells in the retina. Electroretinography (ERG) is a diagnostic tool that measures the electrical activity of the retina in response to light stimuli, and it can help to determine the function of these cells. A normal ERG response consists of two waves, the a-wave and the b-wave, which reflect the activity of the photoreceptor cells and the bipolar and Muller cells, respectively. Despite the growing availability of next-generation sequencing (NGS) technology, identifying the precise genetic mutation causing an IRD can be challenging and costly. However, certain types of IRDs present with unique ERG features that can help guide genetic testing. By combining these ERG findings with other clinical information, such as on family history and retinal imaging, physicians can effectively narrow down the list of candidate genes to be sequenced, thereby reducing the cost of genetic testing. This review article focuses on certain types of IRDs with unique ERG features. We will discuss the pathophysiology and clinical presentation of, and ERG findings on, these disorders, emphasizing the unique role ERG plays in their diagnosis and genetic testing.

Identification of Candidate Genes of Familial Multiple Idiopathic Cervical Root Resorption

IntroductionMultiple idiopathic cervical root resorption (MICRR) is a disease with an unknown etiology that causes invasive cervical root resorption in multiple teeth. Although previous MICRR genomic studies have identified candidate gene variants, the etiology of the condition remains poorly understood. In the present study, we investigated the genetic causality of MICRR to explore candidate variants. MethodsSaliva samples from a family containing 2 affected and two unaffected subjects with the dominant transmission of MICRR were subjected to whole-exome sequencing. ResultsAs a result, we identified novel candidate variants of 10 genes. Each variant was confirmed by Sanger sequencing. Among them, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines classified doublecortin domain containing 1 (c.1099 C > T) and β-defensin 114 (c.189 T > G) as “pathogenic,” and solute carrier family 45 member 2 (c.152_153del) as “likely pathogenic.” ConclusionsThese results provide new insight to help clarify the pathogenesis of MICRR, and the variants could be applied for further investigation to understand invasive cervical root resorption.

Identification and application of a candidate gene AhAftr1 for aflatoxin production resistance in peanut seed (Arachis hypogaea L.)

IntroductionPeanut is susceptible to infection of Aspergillus fungi and conducive to aflatoxin contamination, hence developing aflatoxin-resistant variety is highly meaningful. Identifying functional genes or loci conferring aflatoxin resistance and molecular diagnostic marker are crucial for peanut breeding. ObjectivesThis work aims to (1) identify candidate gene for aflatoxin production resistance, (2) reveal the related resistance mechanism, and (3) develop diagnostic marker for resistance breeding program. MethodsResistance to aflatoxin production in a recombined inbred line (RIL) population derived from a high-yielding variety Xuhua13 crossed with an aflatoxin-resistant genotype Zhonghua 6 was evaluated under artificial inoculation for three consecutive years. Both genetic linkage analysis and QTL-seq were conducted for QTL mapping. The candidate gene was further fine-mapped using a secondary segregation mapping population and validated by transgenic experiments. RNA-Seq analysis among resistant and susceptible RILs was used to reveal the resistance pathway for the candidate genes. ResultsThe major effect QTL qAFTRA07.1 for aflatoxin production resistance was mapped to a 1.98 Mbp interval. A gene, AhAftr1 (Arachis hypogaea Aflatoxin resistance 1), was detected structure variation (SV) in leucine rich repeat (LRR) domain of its production, and involved in disease resistance response through the effector-triggered immunity (ETI) pathway. Transgenic plants with overexpression of AhAftr1(ZH6) exhibited 57.3% aflatoxin reduction compared to that of AhAftr1(XH13). A molecular diagnostic marker AFTR.Del.A07 was developed based on the SV. Thirty-six lines, with aflatoxin content decrease by over 77.67% compared to the susceptible control Zhonghua12 (ZH12), were identified from a panel of peanut germplasm accessions and breeding lines through using AFTR.Del.A07. ConclusionOur findings would provide insights of aflatoxin production resistance mechanisms and laid meaningful foundation for further breeding programs.

An Outlook on GWAS with a Special Focus on Solanaceous Vegetable Crops – A Review

The commercial solanaceous group of vegetables viz., Tomato, Brinjal, Peppers, and Potatoes hold a prime position among all other vegetables in terms of cultivation and consumption worldwide. These vegetables are consumed fresh by all strata of people and are also used as raw materials in the processing industries. Hence, most plant breeders have a keen interest in the crop improvement of these crops emphasizing yield improvement, quality and nutraceuticals enrichment and imparting resistance to various biotic and abiotic stresses in accordance with climate change. Most of the desirable traits are polygenic in nature which may have a complex inheritance pattern. It is essential to have clear-cut knowledge of the expression frequencies of multiple genes/alleles governing a particular quantitative trait/phenotype, the methods employed to examine and comprehend the candidate genes governing one or various characteristics in plants are quantitative trait loci mapping and genome-wide association studies. In This review, we have discussed GWAS and its future perspectives and made efforts to tabulate the recent past works done in solanaceous vegetable crops using this approach. GWAS is a attractive strategy that constitutes an important advancement in genetic analysis and has unquestionably proven to be a useful tool in identifying candidate genes, which is justified in this article.

Genomic signatures reveal selection in Chinese and European domesticated geese.

The Swan goose and Greylag goose are species of geese native to East Asia and Europe, respectively, and are widely believed to be the ancestors of Chinese and European domesticated geese. The Yili goose (YL) and European domestic geese originated from the Greylag goose, but the history of domestication is unclear. In this study, we sequenced and analyzed the genome of the YL goose and the Hortobagy goose to combine with other previously sequenced goose populations for in-depth analysis. The population genetic variations in Stone geese, East Zhejiang White Geese, Taihu geese and Zi geese were also identified and compared. The results showed that admixture gene flow existed in the YL geese population, which was introgressed by Chinese geese, suggesting that gene flow events were frequent and widespread among domesticated geese. Further selected sweep analysis identified candidate genes and metabolic pathways that may be related to the differences in morphology. Several genes such as TGFBR3L, CMYA5, FOXD1, ARHGEF28 and SUCLG2 are associated with growth, reproduction and fertility traits. The results of this study will help to understand the genetic characteristics of domestic geese and the genes affecting important traits and provide a basis for the improved breed of domestic geese.

Identification of Candidate Genes that Affect the Contents of 17 Amino Acids in the Rice Grain Using a Genome-Wide Haplotype Association Study

BackgroundThe amino acid content (AAC) of the rice grain is one of the most important determinants of nutritional quality in rice. Understanding the genetic basis of grain AAC and mining favorable alleles of target genes for AAC are important for developing new cultivars with improved nutritional quality.ResultsUsing a diverse panel of 164 accessions genotyped by 32 M SNPs derived from 3 K Rice Genome Project, we extracted 1,123,603 high quality SNPs in 44,248 genes and used them to construct haplotypes. We measured the contents of the 17 amino acids that included seven essential amino acids and 10 dispensable amino acids. Through a genome-wide haplotype association study, 261 gene-trait associations containing 174 genes for the 17 components of AAC were detected, and 34 of these genes were associated with at least two components. Furthermore, the associated SNPs in genes were also identified by a traditional genome-wide association study to identify the key natural variations in the specific genes.ConclusionsThe genome-wide haplotype association study allowed us to detected candidate genes directly and to identify key natural genetic variation as well. In the present study, twelve genes have been cloned, and 34 genes were associated with at least two components, suggesting that the genome-wide haplotype association study approach used in the current study is an efficient way to identify candidate genes for target traits. The identified candidate genes, favorable haplotypes, and key natural variations affecting AAC provide valuable resources for further functional characterization and genetic improvement of rice nutritional quality.

Bioinformatics Analysis and Screening of Potential Target Genes Related to the Lung Cancer Prognosis.

Several genes have been validated as molecular targets for gene therapy in lung cancer. We screened target genes that affect survival of patients with lung cancer. Data on gene expression in normal lung tissues/lung adenocarcinoma (LUAD) samples were acquired from Genotype-Tissue Expression (GTEx)/The Cancer Genome Atlas (TCGA) databases and merged to expand the sample size, followed by differential analysis of the merged expression data and acquisition of differentially expressed genes. Survival and simple Cox analyses were used to screen for genes affecting LUAD survival. Protein-protein interaction/multivariable Cox analyses were utilized, and a risk model was established. Candidate genes expression levels in cancer/paracancerous tissues of lung cancer patients, and BEAS-2B/A549/HCC95 cells were measured by RT-qPCR/Western blot. Survival analysis of candidate genes was conducted in LUAD samples collected from TCGA. Among 947 genes differentially expressed in LUAD, 151 were correlated with patient survival, and 116 might act as risk factors for LUAD. The 7 identified candidate genes (TOP2A, TK1, KIF4A, ANLN, KIF2C, ASF1B, CCNB1) were high-risk genes playing possible roles in LUAD. These genes were differentially expressed in lung cancer and were associated with TNM stages (III - IV)/differentiation grade/lymph node metastasis/distant metastasis, which affected lung cancer patient survival. P2A, TK1, KIF4A, ANLN, KIF2C, ASF1B and CCNB1 were highly-expressed in LUAD/lung squamous cell carcinoma (LUSC) and correlated with LUAD patient survival. This study contributes to better understanding of the prognostic regulation mechanism in LUAD and the screening of target genes for clinical treatment.

Candidate genes associated with heat stress and breeding strategies to relieve its effects in dairy cattle: a deeper insight into the genetic architecture and immune response to heat stress.

The need for food products of animal origin is increasing worldwide. Satisfying these needs in a way that has minimal impact on the environment requires cutting-edge technologies and techniques to enhance the genetic quality of cattle. Heat stress (HS), in particular, is affecting dairy cattle with increasing frequency and severity. As future climatic challenges become more evident, identifying dairy cows that are more tolerant to HS will be important for breeding dairy herds that are better adapted to future environmental conditions and for supporting the sustainability of dairy farming. While research into the genetics of HS in the context of the effect of global warming on dairy cattle is gaining momentum, the specific genomic regions involved in heat tolerance are still not well documented. Advances in omics information, QTL mapping, transcriptome profiling and genome-wide association studies (GWAS) have identified genomic regions and variants associated with tolerance to HS. Such studies could provide deeper insights into the genetic basis for response to HS and make an important contribution to future breeding for heat tolerance, which will help to offset the adverse effects of HS in dairy cattle. Overall, there is a great interest in identifying candidate genes and the proportion of genetic variation associated with heat tolerance in dairy cattle, and this area of research is currently very active worldwide. This review provides comprehensive information pertaining to some of the notable recent studies on the genetic architecture of HS in dairy cattle, with particular emphasis on the identified candidate genes associated with heat tolerance in dairy cattle. Since effective breeding programs require optimal knowledge of the impaired immunity and associated health complications caused by HS, the underlying mechanisms by which HS modulates the immune response and renders animals susceptible to various health disorders are explained. In addition, future breeding strategies to relieve HS in dairy cattle and improve their welfare while maintaining milk production are discussed.

Genome-wide association studies: an intuitive solution for SNP identification and gene mapping in trees.

Analysis of natural diversity in wild/cultivated plants can be used to understand the genetic basis for plant breeding programs. Recent advancements in DNA sequencing have expanded the possibilities for genetically altering essential features. There have been several recently disclosed statistical genetic methods for discovering the genes impacting target qualities. One of these useful methods is the genome-wide association study (GWAS), which effectively identifies candidate genes for a variety of plant properties by examining the relationship between a molecular marker (such as SNP) and a target trait. Conventional QTL mapping with highly structured populations has major limitations. The limited number of recombination events results in poor resolution for quantitative traits. Only two alleles at any given locus can be studied simultaneously. Conventional mapping approach fails to work in perennial plants and vegetatively propagated crops. These limitations are sidestepped by association mapping or GWAS. The flexibility of GWAS comes from the fact that the individuals being examined need not be linked to one another, allowing for the use of all meiotic and recombination events to increase resolution. Phenotyping, genotyping, population structure analysis, kinship analysis, and marker-trait association analysis are the fundamental phases of GWAS. With the rapid development of sequencing technologies and computational methods, GWAS is becoming a potent tool for identifying the natural variations that underlie complex characteristics in crops. The use of high-throughput sequencing technologies along with genotyping approaches like genotyping-by-sequencing (GBS) and restriction site associated DNA (RAD) sequencing may be highly useful in fast-forward mapping approach like GWAS. Breeders may use GWAS to quickly unravel the genomes through QTL and association mapping by taking advantage of natural variances. The drawbacks of conventional linkage mapping can be successfully overcome with the use of high-resolution mapping and the inclusion of multiple alleles in GWAS.

Longitudinal scRNA-seq analysis in mouse and human informs optimization of rapid mouse astrocyte differentiation protocols.

Macroglia (astrocytes and oligodendrocytes) are required for normal development and function of the central nervous system, yet many questions remain about their emergence during the development of the brain and spinal cord. Here we used single-cell/single-nucleus RNA sequencing (scRNA-seq/snRNA-seq) to analyze over 298,000 cells and nuclei during macroglia differentiation from mouse embryonic and human-induced pluripotent stem cells. We computationally identify candidate genes involved in the fate specification of glia in both species and report heterogeneous expression of astrocyte surface markers across differentiating cells. We then used our transcriptomic data to optimize a previous mouse astrocyte differentiation protocol, decreasing the overall protocol length and complexity. Finally, we used multi-omic, dual single-nuclei (sn)RNA-seq/snATAC-seq analysis to uncover potential genomic regulatory sites mediating glial differentiation. These datasets will enable future optimization of glial differentiation protocols and provide insight into human glial differentiation.

Genome and transcriptome analyses reveal genes involved in the formation of fine ridges on petal epidermal cells in Hibiscus trionum.

Hibiscus trionum, commonly known as the 'Flower of an Hour', is an easily cultivated plant in the Malvaceae family that is widespread in tropical and temperate regions, including drylands. The purple base part of its petal exhibits structural colour due to the fine ridges on the epidermal cell surface, and the molecular mechanism of ridge formation has been actively investigated. We performed genome sequencing of H. trionum using a long-read sequencing technology with transcriptome and pathway analyses to identify candidate genes for fine structure formation. The ortholog of AtSHINE1, which is involved in the biosynthesis of cuticular wax in Arabidopsis thaliana, was significantly overexpressed in the iridescent tissue. In addition, orthologs of AtCUS2 and AtCYP77A, which contribute to cutin synthesis, were also overexpressed. Our results provide important insights into the formation of fine ridges on epidermal cells in plants using H. trionum as a model.

The role of WRKY transcription factors, FaWRKY29 and FaWRKY64, for regulating Botrytis fruit rot resistance in strawberry (Fragaria × ananassa Duch.)

BackgroundThe cultivated strawberry (Fragaria × ananassa Duch.) is one of the most economically important horticultural crops worldwide. Botrytis fruit rot (BFR) caused by the necrotrophic fungal pathogen Botrytis cinerea is the most devasting disease of cultivated strawberries. Most commercially grown strawberry varieties are susceptible to BFR, and controlling BFR relies on repeated applications of various fungicides. Despite extensive efforts, breeding for BFR resistance has been unsuccessful, primarily due to lack of information regarding the mechanisms of disease resistance and genetic resources available in strawberry.ResultsUsing a reverse genetics approach, we identified candidate genes associated with BFR resistance and screened Arabidopsis mutants using strawberry isolates of B. cinerea. Among the five Arabidopsis T-DNA knockout lines tested, the mutant line with AtWRKY53 showed the greatest reduction in disease symptoms of BFR against the pathogen. Two genes, FaWRKY29 and FaWRKY64, were identified as orthologs in the latest octoploid strawberry genome, ‘Florida Brilliance’. We performed RNAi-mediated transient assay and found that the disease frequencies were significantly decreased in both FaWRKY29- and FaWRKY64-RNAi fruits of the strawberry cultivar, ‘Florida Brilliance’. Furthermore, our transcriptomic data analysis revealed significant regulation of genes associated with ABA and JA signaling, plant cell wall composition, and ROS in FaWRKY29 or FaWRKY64 knockdown strawberry fruits in response to the pathogen.ConclusionOur study uncovered the foundational role of WRKY transcription factor genes, FaWRKY29 and FaWRKY64, in conferring resistance against B. cinerea. The discovery of susceptibility genes involved in BFR presents significant potential for developing resistance breeding strategies in cultivated strawberries, potentially leveraging CRISPR-based gene editing techniques.

Deep learning to obtain high-throughput morphological phenotypes and its genetic correlation with swimming performance in juvenile large yellow croaker

Breeding for swimming performance in fish may cause changes in morphological traits in offspring, which are not only related to industrial efficiency, but also affect animal welfare. However, the genetic correlation between swimming performance and morphological traits in juvenile large yellow croaker remains unclear, and traditional morphological traits collection is time-consuming and laborious. Deep learning offers new opportunities for high-throughput phenomics, especially for complex morphological traits. In this study, the automatic High-Resolution Network (HRNet) based on a deep learning approach was used for the first time to effectively detect the morphological traits of juvenile large yellow croaker. We assessed the swimming performance (Ucrit) of 1300 juvenile fish, and conducted a genome-wide association study (GWAS) and genetic parameters study on the morphological traits of 383 juvenile fish using a 55 K SNP array. The morphological traits data of 383 fish comes from the predicted results of the HRNet model. The results showed that: (1) All of the 10 morphological traits showed positively correlated with Ucrit, and mostly positive genetic correlated with Ucrit; (2) The heritability of all 10 morphological traits was low to moderate; (3) We identified 4 SNPs significantly associated with morphological traits, and identified candidate genes including sox8, setd6, and ctbp2, and enriched significant pathways including Notch signaling pathway. In conclusion, this study provides an efficient and multi-context adaptive HRNet based on deep learning for high-throughput morphological traits detection of juvenile large yellow croaker, and analyses the genetic basis between morphological traits and swimming performance for this species, which provides a new understanding of the genetic basis of morphological traits of large yellow croaker, and provides a basis for breeding programs.

CCDC50, an essential driver involved in tumorigenesis, is a potential severity marker of diffuse large B cell lymphoma

Diffuse Large B Cell Lymphoma (DLBCL) is the most common form of blood cancer. Among the subtypes, the activated B-cell (ABC) subtype is typically more aggressive and associated with worse outcomes. However, the underlying mechanisms are not fully understood. In this study, we performed microarray analysis to identify potential ABC-DLBCL-associated genes. We employed Kaplan–Meier methods and cox univariate analysis to explore the prognostic value of the identified candidate gene Coiled-coil domain containing 50 (CCDC50). Additionally, we used DLBCL cell lines and mouse models to explore the functions and mechanisms of CCDC50. Finally, we isolated CCDC50-bearing exosomes from clinical patients to study the correlation between these exosomes and disease severity. Our results demonstrated that CCDC50 not only showed significantly positive correlations with ABC subtype, tumor stage and number of extranodal sites, but also suggested poor outcomes in DLBCL patients. We further found that CCDC50 promoted ABC-DLBCL proliferation in vitro and in vivo. Mechanistically, CCDC50 inhibited ubiquitination-mediated c-Myc degradation by stimulating the PI3K/AKT/GSK-3β pathway. Moreover, CCDC50 expression was positively correlated with c-Myc at protein levels in DLBCL patients. Additionally, in two clinical cohorts, the plasma CCDC50-positive exosomes differentiated DLBCL subtypes robustly (AUC > 0.80) and predicted disease severity effectively (p < 0.05). Our findings suggest that CCDC50 likely drives disease progression in ABC-DLBCL patients, and the CCDC50-bearing exosome holds great potential as a non-invasive biomarker for subtype diagnosis and prognosis prediction of DLBCL patients.

Evolutionary history and seascape genomics of Harbour porpoises (Phocoena phocoena) across environmental gradients in the North Atlantic and adjacent waters.

The Harbour porpoise (Phocoena phocoena) is a highly mobile cetacean species primarily occurring in coastal and shelf waters across the Northern hemisphere. It inhabits heterogeneous seascapes broadly varying in salinity and temperature. Here, we produced 74 whole genomes at intermediate coverage to study Harbour porpoise's evolutionary history and investigate the role of local adaptation in the diversification into subspecies and populations. We identified ~6 million high quality SNPs sampled at eight localities across the North Atlantic and adjacent waters, which we used for population structure, demographic and genotype-environment association analyses. Our results suggest a genetic differentiation between three subspecies (P.p. relicta, P.p. phocoena and P.p. meridionalis), and three distinct populations within P.p. phocoena: Atlantic, Belt Sea and Proper Baltic Sea. Effective population size and Tajima's D suggest population contraction in Black Sea and Iberian porpoises, but expansion in the P.p. phocoena populations. Phylogenetic trees indicate post-glacial colonization from a southern refugium. Genotype-environment association analysis identified salinity as major driver in genomic variation and we identified candidate genes putatively underlying adaptation to different salinity. Our study highlights the value of whole genome resequencing to unravel subtle population structure in highly mobile species, shows how strong environmental gradients and local adaptation may lead to population differentiation, and how neutral and adaptive markers can give different perspectives on population subdivision. The results have great conservation implications as we found inbreeding and low genetic diversity in the endangered Black Sea subspecies and identified the critically endangered Proper Baltic Sea porpoises as a separate population.

Investigation into Molecular Brain Aging in Senescence-Accelerated Mouse (SAM) Model Employing Whole Transcriptomic Analysis in Search of Potential Molecular Targets for Therapeutic Interventions.

With the progression of an aging society, cognitive aging has emerged as a pressing concern necessitating attention. The senescence-accelerated mouse-prone 8 (SAMP8) model has proven instrumental in investigating the early stages of cognitive aging. Through an extensive examination of molecular changes in the brain cortex, utilizing integrated whole-genome transcriptomics, our principal aim was to uncover potential molecular targets with therapeutic applications and relevance to drug screening. Our investigation encompassed four distinct conditions, comparing the same strain at different time points (1 year vs. 16 weeks) and the same time point across different strains (SAMP8 vs. SAMR1), namely: physiological aging, accelerated aging, early events in accelerated aging, and late events in accelerated aging. Focusing on key functional alterations associated with aging in the brain, including neurogenesis, synapse dynamics, neurometabolism, and neuroinflammation, we identified candidate genes linked to these processes. Furthermore, employing protein-protein interaction (PPI) analysis, we identified pivotal hub genes involved in interactions within these functional domains. Additionally, gene-set perturbation analysis allowed us to uncover potential upstream genes or transcription factors that exhibited activation or inhibition across the four conditions. In summary, our comprehensive analysis of the SAMP8 mouse brain through whole-genome transcriptomics not only deepens our understanding of age-related changes but also lays the groundwork for a predictive model to facilitate drug screening for cognitive aging.

Candidate genes for domestication and resistance to cold climate according to whole genome sequencing data of Russian cattle and sheep breeds.

It is known that different species of animals, when living in the same environmental conditions, can form similar phenotypes. The study of the convergent evolution of several species under the influence of the same environmental factor makes it possible to identify common mechanisms of genetic adaptation. Local cattle and sheep breeds have been formed over thousands of years under the influence of domestication, as well as selection aimed at adaptation to the local environment and meeting human needs. Previously, we identified a number of candidate genes in genome regions potentially selected during domestication and adaptation to the climatic conditions of Russia, in local breeds of cattle and sheep using whole genome genotyping data. However, these data are of low resolution and do not reveal most nucleotide substitutions. The aim of the work was to create, using the whole genome sequencing data, a list of genes associated with domestication, selection and adaptation in Russian cattle and sheep breeds, as well as to identify candidate genes and metabolic pathways for selection for cold adaptation. We used our original data on the search for signatures of selection in the genomes of Russian cattle (Yakut, Kholmogory, Buryat, Wagyu) and sheep (Baikal, Tuva) breeds. We used the HapFLK, DCMS, FST and PBS methods to identify DNA regions with signatures of selection. The number of candidate genes in potentially selective regions was 946 in cattle and 151 in sheep. We showed that the studied Russian cattle and sheep breeds have at least 10 genes in common, apparently involved in the processes of adaptation/selection, including adaptation to a cold climate, including the ASTN2, PM20D1, TMEM176A, and GLIS1 genes. Based on the intersection with the list of selected genes in at least two Arctic/Antarctic mammal species, 20 and 8 genes, have been identified in cattle and sheep, respectively, that are potentially involved in cold adaptation. Among them, the most promising for further research are the ASPH, NCKAP5L, SERPINF1, and SND1 genes. Gene ontology analysis indicated the existence of possible common biochemical pathways for adaptation to cold in domestic and wild mammals associated with cytoskeleton disassembly and apoptosis.

Using High-Throughput Phenotyping Analysis to Decipher the Phenotypic Components and Genetic Architecture of Maize Seedling Salt Tolerance.

Soil salinization is a worldwide problem that limits agricultural production. It is important to understand the salt stress tolerance ability of maize seedlings and explore the underlying related genetic resources. In this study, we used a high-throughput phenotyping platform with a 3D laser sensor (Planteye F500) to identify the digital biomass, plant height and normalized vegetation index under normal and saline conditions at multiple time points. The result revealed that a three-leaf period (T3) was identified as the key period for the phenotypic variation in maize seedlings under salt stress. Moreover, we mapped the salt-stress-related SNPs and identified candidate genes in the natural population via a genome-wide association study. A total of 44 candidate genes were annotated, including 26 candidate genes under normal conditions and 18 candidate genes under salt-stressed conditions. This study demonstrates the feasibility of using a high-throughput phenotyping platform to accurately, continuously quantify morphological traits of maize seedlings in different growing environments. And the phenotype and genetic information of this study provided a theoretical basis for the breeding of salt-resistant maize varieties and the study of salt-resistant genes.

Transposon sequencing identifies genes impacting Staphylococcus aureus invasion in a human macrophage model.

Staphylococcus aureus is a facultative intracellular pathogen in many host cell types, facilitating its persistence in chronic infections. The genes contributing to intracellular pathogenesis have not yet been fully enumerated. Here, we cataloged genes influencing S. aureus invasion and survival within human THP-1 derived macrophages using two laboratory strains (ATCC2913 and JE2). We developed an in vitro transposition method to produce highly saturated transposon mutant libraries in S. aureus and performed transposon insertion sequencing (Tn-Seq) to identify candidate genes with significantly altered abundance following macrophage invasion. While some significant genes were strain-specific, 108 were identified as common across both S. aureus strains, with most (n = 106) being required for optimal macrophage infection. We used CRISPR interference (CRISPRi) to functionally validate phenotypic contributions for a subset of genes. Of the 20 genes passing validation, seven had previously identified roles in S. aureus virulence, and 13 were newly implicated. Validated genes frequently evidenced strain-specific effects, yielding opposing phenotypes when knocked down in the alternative strain. Genomic analysis of de novo mutations occurring in groups (n = 237) of clonally related S. aureus isolates from the airways of chronically infected individuals with cystic fibrosis (CF) revealed significantly greater in vivo purifying selection in conditionally essential candidate genes than those not associated with macrophage invasion. This study implicates a core set of genes necessary to support macrophage invasion by S. aureus, highlights strain-specific differences in phenotypic effects of effector genes, and provides evidence for selection of candidate genes identified by Tn-Seq analyses during chronic airway infection in CF patients in vivo.