Genetically Research Articles

The genetics of plant-plant interactions and their cascading effects on agroecosystem - from model plants to application.

Plants are typically surrounded by neighboring individuals in agricultural fields or natural environments. In such circumstances, plant-plant interactions (PPI) are ubiquitous and represent not only important evolutionary forces but also have consequences on (agro-)ecosystem functioning, such as increased productivity and resistance. However, many mechanisms underlying these PPIs remain poorly understood. Recently, new genomic technologies and tools, such as genome-wide association studies, have facilitated genetic approaches to study PPIs, particularly among conspecific individuals. Here, we highlight emerging issues and advances in the field by focusing on three different aspects. First, we overview the current status of genetic mapping studies on PPIs and pinpoint that these studies open a new opportunity that is relevant to agriculture and breeding. Second, we introduce two proof-of-concept studies in Arabidopsis thaliana, in which genetic differences among plants improved the functioning of genotype mixtures. Both studies were able to predict effective mixtures with different experimental designs applied to different outcomes (productivity increase vs. herbivory mitigation). Third, we discuss implications from these case studies about how PPIs have cascading effects that propagate to higher levels of biological organization, such as populations or communities. At the population level, plant yield or resistance can be optimized through breeding that achieves reduced competition or push-pull protection systems, respectively. At the community level, these population-level changes may have further beneficial effects on plant-associated organisms. Overall, we suggest that the increasing availability of genomic resources will improve our understanding of PPIs and thereby contribute to the management of crops or semi-natural ecosystems.

Photoexcited Cryptochrome 1 Interacts With SPCHLESS to Regulate Stomatal Development in Arabidopsis.

Stomata are epidermal openings that facilitate plant-atmosphere gas and water exchange during photosynthesis, respiration and water evaporation. SPEECHLESS (SPCH) is a master basic helix-loop-helix (bHLH) transcription factor that determines the initiation of stomatal development. It is known that blue light promotes stomatal development through the blue light photoreceptor cryptochromes (CRYs, CRY1 and CRY2). Whether CRYs regulate stomatal development through directly modulating SPCH is unknown. Here, we demonstrate by biochemical studies that CRY1 physically interacts with SPCH in a blue light-dependent manner. Genetic studies show that SPCH acts downstream of CRY1 to promote stomatal development in blue light. Furthermore, we show that CRY1 enhances the DNA-binding activity of SPCH and promotes the expression of its target genes in blue light. These results suggest that the mechanism by which CRY1 promotes stomatal development involves positive regulation of the DNA-binding activity of SPCH, which is likely mediated by blue light-induced CRY1-SPCH interaction. The precise regulation of SPCH DNA-binding activity by CRY1 may allow plants to optimize stomatal density and pattern according to ambient light conditions.

Genetic variation in CCDC93 is associated with elevated central systolic blood pressure, impaired arterial relaxation, and mitochondrial dysfunction.

Genetic studies of blood pressure (BP) traits to date have been performed on conventional measures by brachial cuff sphygmomanometer for systolic BP (SBP) and diastolic BP, integrating several physiologic occurrences. Genetic associations with central SBP (cSBP) have not been well-studied. Genetic discovery studies of BP have been most often performed in European-ancestry samples. Here, we investigated genetic associations with cSBP in a Chinese population and functionally validated the impact of a novel associated coiled-coil domain containing 93 (CCDC93) gene on BP regulation. An exome-wide association study (EWAS) was performed using a mixed linear model of non-invasive cSBP and peripheral BP traits in a Han Chinese population (N = 5,954) from Beijing, China genotyped with a customized Illumina ExomeChip array. We identified four SNP-trait associations with three SNPs, including two novel associations (rs2165468-SBP and rs33975708-cSBP). rs33975708 is a coding variant in the CCDC93 gene, c.535C>T, p.Arg179Cys (MAF = 0.15%), and was associated with increased cSBP (β = 29.3 mmHg, P = 1.23x10-7). CRISPR/Cas9 genome editing was used to model the effect of Ccdc93 loss in mice. Homozygous Ccdc93 deletion was lethal prior to day 10.5 of embryonic development. Ccdc93+/- heterozygous mice were viable and morphologically normal, with 1.3-fold lower aortic Ccdc93 protein expression (P = 0.0041) and elevated SBP as compared to littermate Ccdc93+/+ controls (110±8 mmHg vs 125±10 mmHg, P = 0.016). Wire myography of Ccdc93+/- aortae showed impaired acetylcholine-induced relaxation and enhanced phenylephrine-induced contraction. RNA-Seq transcriptome analysis of Ccdc93+/- mouse thoracic aortae identified significantly enriched pathways altered in fatty acid metabolism and mitochondrial metabolism. Plasma free fatty acid levels were elevated in Ccdc93+/- mice (96±7mM vs 124±13mM, P = 0.0031) and aortic mitochondrial dysfunction was observed through aberrant Parkin and Nix protein expression. Together, our genetic and functional studies support a novel role of CCDC93 in the regulation of BP through its effects on vascular mitochondrial function and endothelial function.

Genetics and Epigenetic in Mental Health

Genetics and epigenetics play critical roles in mental health, offering insights into the complex interplay between biological predisposition and environmental influences in the development and progression of mental disorders. Genetic studies have identified numerous risk loci associated with conditions such as schizophrenia, bipolar disorder, and depression, highlighting the polygenic nature of these illnesses. However, the presence of genetic risk factors alone does not fully account for the variability in disease onset, severity, or response to treatment. This gap is increasingly understood through the lens of epigenetics, which involves heritable changes in gene expression that do not alter the DNA sequence itself but are influenced by environmental factors, such as stress, diet, and exposure to toxins. Epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNAs, can modulate gene activity in response to external stimuli, leading to long-lasting effects on brain function and behavior. These processes are particularly important during critical periods of brain development, where epigenetic modifications can shape neural circuits involved in emotion regulation, cognition, and stress response. Emerging research suggests that the interaction between genetic predisposition and epigenetic changes contributes to the heterogeneity observed in mental health disorders, explaining why individuals with similar genetic risks can have different outcomes. Understanding these intricate genetic and epigenetic networks is essential for developing personalized therapeutic strategies, which could revolutionize the prevention, diagnosis, and treatment of mental health conditions. Advances in this field hold the promise of identifying biomarkers for early intervention and creating targeted interventions that consider an individual’s unique genetic and epigenetic profile, ultimately improving mental health outcomes on a global scale.

Decoding the genetic landscape of autism: A comprehensive review.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings. Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD, influencing both diagnosis and therapeutic strategies. To explore the genetic architecture of ASD, elucidate mechanistic insights into genetic mutations, and examine gene-environment interactions. A comprehensive systematic review was conducted, integrating findings from studies on genetic variations, epigenetic mechanisms (such as DNA methylation and histone modifications), and emerging technologies [including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 and single-cell RNA sequencing]. Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar. Genetic studies have identified numerous risk genes and mutations associated with ASD, yet many cases remain unexplained by known factors, suggesting undiscovered genetic components. Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving. Epigenetic modifications, particularly DNA methylation and non-coding RNAs, also play significant roles in ASD pathogenesis. Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data. Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments. Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice. Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies, ultimately enhancing outcomes for individuals affected by ASD.

"The Reference Genome Of The Kidnapper Ant, Polyergus Mexicanus".

Polyergus kidnapper ants are widely distributed, but relatively uncommon, throughout the Holarctic, spanning an elevational range from sea level to over 3000 m. These species are well known for their obligate social parasitism with various Formica ant species, which they kidnap in dramatic, highly coordinated raids. Kidnapped Formica larvae and pupae become integrated into the Polyergus colony where they develop into adults and perform nearly all of the necessary colony tasks for the benefit of their captors. In California, Polyergus mexicanus is the most widely distributed Polyergus, but recent evidence has identified substantial genetic polymorphism within this species, including genetically divergent lineages associated with the use of different Formica host species. Given its unique behavior and genetic diversity, Polyergus mexicanus plays a critical role in maintaining ecosystem balance by influencing the population dynamics and genetic diversity of its host ant species, Formica, highlighting its conservation value and importance in the context of biodiversity preservation. Here, we present a high-quality genome assembly of P. mexicanus from a sample collected in Plumas County, CA, USA, in the foothills of the central Sierra Nevada. This genome assembly consists of 364 scaffolds spanning 252.31Mb, with contig N50 of 481,250kb, scaffold N50 of 10.36Mb, and BUSCO completeness of 95.4%. We also assembled the genome of the Wolbachia endosymbiont of P. mexicanus - a single, circular contig spanning 1.23Mb. These genome sequences provide essential resources for future studies of conservation genetics, population genetics, speciation, and behavioral ecology in this charismatic social insect.

Association of LIN28B Gene Polymorphisms with Intrauterine Adhesions in Patients after Curettage Abortion.

Background/Objectives: Intrauterine adhesion (IUA) is characterized by endometrial fibrocyte hyperplasia. The LIN28B gene is associated with many proliferative diseases. However, its association with IUA is entirely unknown. We hypothesized that LIN28B gene polymorphisms are responsible for IUA susceptibility after curettage abortion. Methods: In this genetic association study, We genotyped two common polymorphisms (rs369065 C>T and rs314280 A>G) in 107 patients with IUA and 270 controls without IUA after curettage abortion from a Chinese population between July 2022 and May 2023 and analyzed their associations with IUA risk using multiple logistic regression models. Results: The carriers of genotype rs314280 AA of the LIN28B gene showed an increased risk of IUA (AOR [adjusted odds ratio] = 2.12, 95% CI [confidence interval] = 1.151-3.903), compared to GG+GA genotypes. Further stratification analyses showed that the deleterious role of the rs314280 AA genotype was more evident in patients with fewer than four pregnancies (AOR = 2.740, 95% CI = 1.355-5.540), fewer than two births (AOR = 2.676, 95% CI = 1.300-5.509), and fibrous (AOR = 2.082, 95% CI = 1.084-3.997) and muscular adhesions (AOR = 3.887, 95% CI = 1.116-13.540). However, the rs369065 T>C polymorphism of the LIN28B gene was not significantly associated with the occurrence of IUA. Conclusions: The rs314280 AA genotype of the LIN28B gene is associated with an increased risk of IUA in patients after curettage abortion, especially in those with fewer pregnancies or parities and higher disease severity. Our findings implicate a precise choice of clinical counseling and decision-making of IUA, thereby protecting female reproduction.

Identification of Insertion and Deletion (InDel) Markers for Chickpea (Cicer arietinum L.) Based on Double-Digest Restriction Site-Associated DNA Sequencing.

Enhancing the marker repository and the development of breeder-friendly markers in chickpeas is important in relation to chickpea genomics-assisted breeding applications. Insertion-deletion (InDel) markers are widely distributed across genomes and easily observed with specifically designed primers, leading to less time, cost, and labor requirements. In light of this, the present study focused on the identification and development of InDel markers through the use of double-digest restriction site-associated DNA sequencing (ddRADSeq) data from 20 chickpea accessions. Bioinformatic analysis identified 20,700 InDel sites, including 15,031 (72.61%) deletions and 5669 (27.39%) insertions, among the chickpea accessions. The InDel markers ranged from 1 to 25 bp in length, while single-nucleotide-length InDel markers were found to represent the majority of the InDel sites and account for 79% of the total InDel markers. However, we focused on InDel markers wherein the length was greater than a single nucleotide to avoid any read or alignment errors. Among all of the InDel markers, 96.1% were less than 10 bp, 3.6% were between 10 and 20 bp, and 0.3% were more than 20 bp in length. We examined the InDel markers that were 10 bp and longer for the development of InDel markers based on a consideration of the genomic distribution and low-cost genotyping with agarose gels. A total of 29 InDel regions were selected, and primers were successfully designed to evaluate their efficiency. Annotation analysis of the InDel markers revealed them to be found with the highest frequency in the intergenic regions (82.76%), followed by the introns (6.90%), coding sequences (6.90%), and exons (3.45%). Genetic diversity analysis demonstrated that the polymorphic information content of the markers varied from 0.09 to 0.37, with an average of 0.20. Taken together, these results showed the efficiency of InDel marker development for chickpea genetic and genomic studies using the ddRADSeq method. The identified markers might prove valuable for chickpea breeders.

Role of the X Chromosome in Alzheimer Disease Genetics

The X chromosome has remained enigmatic in Alzheimer disease (AD), yet it makes up 5% of the genome and carries a high proportion of genes expressed in the brain, making it particularly appealing as a potential source of unexplored genetic variation in AD. To perform the first large-scale X chromosome-wide association study (XWAS) of AD. This was a meta-analysis of genetic association studies in case-control, family-based, population-based, and longitudinal AD-related cohorts from the US Alzheimer's Disease Genetics Consortium, the Alzheimer's Disease Sequencing Project, the UK Biobank, the Finnish health registry, and the US Million Veterans Program. Risk of AD was evaluated through case-control logistic regression analyses. Data were analyzed between January 2023 and March 2024. Genetic data available from high-density single-nucleotide variant microarrays and whole-genome sequencing and summary statistics for multitissue expression and protein quantitative trait loci available from published studies were included, enabling follow-up genetic colocalization analyses. A total of 1 629 863 eligible participants were selected from referred and volunteer samples, 477 596 of whom were excluded for analysis exclusion criteria. The number of participants who declined to participate in original studies was not available. Risk of AD, reported as odds ratios (ORs) with 95% CIs. Associations were considered at X chromosome-wide (P < 1 × 10-5) and genome-wide (P < 5 × 10-8) significance. Primary analyses are nonstratified, while secondary analyses evaluate sex-stratified effects. Analyses included 1 152 284 participants of non-Hispanic White, European ancestry (664 403 [57.7%] female and 487 881 [42.3%] male), including 138 558 individuals with AD. Six independent genetic loci passed X chromosome-wide significance, with 4 showing support for links between the genetic signal for AD and expression of nearby genes in brain and nonbrain tissues. One of these 4 loci passed conservative genome-wide significance, with its lead variant centered on an intron of SLC9A7 (OR, 1.03; 95% CI, 1.02-1.04) and colocalization analyses prioritizing both the SLC9A7 and nearby CHST7 genes. Of these 6 loci, 4 displayed evidence for escape from X chromosome inactivation with regard to AD risk. This large-scale XWAS of AD identified the novel SLC9A7 locus. SLC9A7 regulates pH homeostasis in Golgi secretory compartments and is anticipated to have downstream effects on amyloid β accumulation. Overall, this study advances our knowledge of AD genetics and may provide novel biological drug targets. The results further provide initial insights into elucidating the role of the X chromosome in sex-based differences in AD.

Intermittent Fasting-Induced Orm2 Promotes Adipose Browning via the GP130/IL23R-p38 Cascade.

Intermittent fasting (IF) plays a critical role in mitigating obesity, yet the precise biological mechanisms require further elucidation. Here Orosomucoid 2 (Orm2)is identified as an IF-induced hepatokine that stimulates adipose browning. IF induced Orm2 expression and secretion from the liver through peroxisome proliferator-activated receptor alpha (PPARα). In adipose tissue, Orm2 bound to glycoprotein 130/interleukin 23 receptor (GP130/IL23R)and promoted adipose browning through the activation of p38 mitogen-activated protein kinases (p38-MAPK). In obese mice, Orm2 led to a significant induction of adipose tissue browning and subsequent weight loss, an effect that is not replicated by a mutant variant of Orm2 deficient in GP130/IL23R binding capability. Crucially, genetic association studies in humans identified an obesity-associated Orm2 variant (D178E), which shows decreased GP130/IL23R binding and impaired browning capacity in mice. Overall, the research identifies Orm2 as a promising therapeutic target for obesity, mediating adipose browning through the GP130/IL23R-p38 signalling pathway.

Enhancing genetic association power in endometriosis through unsupervised clustering of clinical subtypes identified from electronic health records.

Endometriosis is a complex and heterogeneous condition affecting 10% of reproductive-age women, and yet, it often goes undiagnosed for several years. Limited observed heritability (7%) of large genetic association studies may be attributable to underlying heterogeneity of disease mechanisms. Therefore, we conducted this study to investigate genetic associations across sub-phenotypes of endometriosis. We performed unsupervised clustering of 4,078 women with endometriosis based on known endometriosis risk factors, symptoms, and concomitant conditions. The clusters were characterized by examining electronic health record (EHR) data and comprehensive chart reviews. We then performed genetic association for each cluster with 39 endometriosis-associated loci (Total Nendometriosis cases = 12,350). We identified five sub-phenotype clusters: (1) pain comorbidities, (2) uterine disorders, (3) pregnancy complications, (4) cardiometabolic comorbidities, and (5) HER-asymptomatic. Bonferroni significant loci included PDLIM5 for the cluster 1, GREB1 for cluster 2, WNT4 for cluster 3, RNLS for cluster 4, and ABO for cluster 5. The difference in associations between the groups suggests complex and varied genetic mechanisms of endometriosis and its symptoms. This study enhances our understanding of the clinical patterns of endometriosis sub-phenotypes, showcasing the innovative approach employed to investigate this complex disease.

Innovative Approaches and Future Directions in the Management and Understanding of Varicose Veins: A Systematic Review.

Varicose veins, a prevalent condition that primarily affects the lower limbs, present significant hurdles in diagnosis and treatment due to their diverse causes. This study dives into the complex hormonal, environmental, and molecular elements that influence varicose vein genesis, emphasizing the need for precise diagnostic methods and changing therapy approaches to improve patient outcomes. It investigates the epidemiology and demographic distribution of varicose veins, delves into their pathophysiology, and assesses diagnostic methods such as duplex ultrasonography and the CEAP classification system. In addition, the study discusses novel therapies such as sclerotherapy and endovenous thermal ablation, as well as the effectiveness of existing diagnostic methods in detecting chronic venous illnesses. By investigating venous wall remodeling and inflammatory pathways, it gives a thorough knowledge of varicose vein formation. The study calls for future research that focuses on patient-centered methods, bioengineering advances, digital health applications, and genetic and molecular studies to improve the accuracy and effectiveness of vascular therapy. As a result, a multidisciplinary literature analysis was done, drawing on insights from vascular medicine, epidemiology, genetics, and pharmacology, to consolidate existing knowledge and identify possibilities to enhance varicose vein diagnosis, treatment, and patient care outcomes.

Comparing Apples and Oranges: Advances in Disease Resistance Breeding of Woody Perennial Fruit Crops.

Apple and citrus are perennial tree fruit crops that are vital for nutritional security and agricultural economy and to achieve the Sustainable Development Goals of the United Nations. Apple scab and fire blight, along with Huanglongbing, canker, and tristeza virus, stand out as their most notorious diseases and annually destabilize fruit supply. An environmentally sound approach to managing these diseases is improving tree resistance through breeding and biotechnology. Perennial fruit tree germplasm collections are distributed globally and offer untapped potential as sources of resistance. However, long juvenility, specific pollination and flowering habits, and extensive outcrossing hinder apple and citrus breeding. Advances in breeding approaches include trans- and cis-genesis, genome editing, and rapid-cycle breeding, which, in addition to conventional crossbreeding, can all facilitate accelerated integration of resistance into elite germplasm. In addition, the global pool of available sources of resistance can be characterized by the existing genetic mapping and gene expression studies for accurate discovery of associated loci, genes, and markers to efficiently include these sources in breeding efforts. We discuss and propose a multitude of approaches to overcome the challenges of breeding for resistance in woody perennials and outline a technical path to reduce the time required for the ultimate deployment of disease-resistant cultivars.

Development and validation of a 66K SNP array for the hard clam (Mercenaria mercenaria)

BackgroundThe hard clam (Mercenaria mercenaria), a marine bivalve distributed along the U.S. eastern seaboard, supports a significant shellfish industry. Overharvest in the 1970s and 1980s led to a reduction in landings. While the transition of industry from wild harvest to aquaculture since that time has enhanced production, it has also exacerbated challenges such as disease outbreaks. In this study, we developed and validated a 66K SNP array designed to advance genetic studies and improve breeding programs in the hard clam, focusing particularly on the development of markers that could be useful in understanding disease resistance and environmental adaptability.ResultsWhole-genome resequencing of 84 individual clam samples and 277 pooled clam libraries yielded over 305 million SNPs, which were filtered down to a set of 370,456 SNPs that were used as input for the design of a 66K SNP array. This medium-density array features 66,543 probes targeting coding and non-coding regions, including 70 mitochondrial SNPs, to capture the extensive genetic diversity within the species. The SNPs were distributed evenly throughout the clam genome, with an average interval of 25,641 bp between SNPs. The array incorporates markers for detecting the clam pathogen Mucochytrium quahogii (formerly QPX), enhancing its utility in disease management. Performance evaluation on 1,904 samples demonstrated a 72.7% pass rate with stringent quality control. Concordance testing affirmed the array's repeatability, with an average agreement of allele calls of 99.64% across multiple tissue types, highlighting its reliability. The tissue-specific analysis demonstrated that some tissue types yield better genotyping results than others. Importantly, the array, including its embedded mitochondrial markers, effectively elucidated complex genetic relationships across different clam groups, both wild populations and aquacultured stocks, showcasing its utility for detailed population genetics studies.ConclusionsThe 66K SNP array is a powerful and robust genotyping tool that offers unprecedented insights into the species’ genomic architecture and population dynamics and that can greatly facilitate hard clam selective breeding. It represents an important resource that has the potential to transform clam aquaculture, thereby promoting industry sustainability and ecological and economic resilience.

Atp1a2 and Kcnj9 are candidate genes underlying sensitivity to oxycodone-induced locomotor activation and withdrawal-induced anxiety-like behaviors in C57BL/6 substrains.

Opioid use disorder is heritable, yet its genetic etiology is largely unknown. C57BL/6J and C57BL/6NJ mouse substrains exhibit phenotypic diversity in the context of limited genetic diversity which together can facilitate genetic discovery. Here, we found C57BL/6NJ mice were less sensitive to oxycodone (OXY)-induced locomotor activation versus C57BL/6J mice in a conditioned place preference paradigm. Narrow-sense heritability was estimated at 0.22-0.31, implicating suitability for genetic analysis. Quantitative trait locus (QTL) mapping in an F2 cross identified a chromosome 1 QTL explaining 7-12% of the variance in OXY locomotion and anxiety-like withdrawal in the elevated plus maze. A second QTL for EPM withdrawal behavior on chromosome 5 near Gabra2 (alpha-2 subunit of GABA-A receptor) explained 9% of the variance. To narrow the chromosome 1 locus, we generated recombinant lines spanning 163-181 Mb, captured the QTL for OXY locomotor traits and withdrawal, and fine-mapped a 2.45-Mb region (170.16-172.61 Mb). Transcriptome analysis identified five, localized striatal cis-eQTL transcripts and two were confirmed at the protein level (KCNJ9, ATP1A2). Kcnj9 codes for a potassium channel (GIRK3) that is a major effector of mu opioid receptor signaling. Atp1a2 codes for a subunit of a Na+/K+ ATPase enzyme that regulates neuronal excitability and shows functional adaptations following chronic opioid administration. To summarize, we identified two candidate genes underlying the physiological and behavioral properties of opioids, with direct preclinical relevance to investigators employing these widely used substrains and clinical relevance to human genetic studies of opioid use disorder.

Use of Maize (Zea maysL.) Mutator Transposon-Induced Mutants of theBonnMuResource for Forward and Reverse Genetics Studies

TheBonnMuresource represents a tagged collection of maize (Zea maysL.)Mutator(Mu) transposon-induced mutants, designed for functional genomics studies. Here, we describe the use of theBonnMucollection for identifying and characterizing mutations. Specifically, we describe workflows for use in both reverse and forward genetics strategies in maize. For reverse genetics, users first acquire aBonnMuF2stock of interest based on data accessible at the Maize Genetics and Genomics Database (MaizeGDB). We provide details here for their subsequent propagation and for the confirmation ofMuinsertions by genotyping via PCR, with the ultimate goal of establishing genotype–phenotype relationships of interest. For forward genetics studies, we describe a workflow that involves a combined approach of Mutant-Seq (Mu-Seq) and bulked segregant RNA-seq (BSR-Seq), to identify the causal gene underlying a mutant phenotype of interest.

Defining and pursuing diversity in human genetic studies

Defining and pursuing diversity in human genetic studies

BonnMu: A Resource for Functional Genomics in Maize (Zea mays L.).

The BonnMu resource is a public transposon-tagged population designed for reverse and forward genetics studies in maize (Zea mays L.). The resource was created by crossing an active Mutator (Mu) transposon line into different inbred lines to induce insertional mutations. The resulting F1 generation was self-pollinated to generate segregating BonnMu F2 stocks. The Mu-tagged BonnMu F2 stocks have insertions in 83% of all annotated maize gene models, and Mu insertion positions and photos of the seedling phenotypes of the segregating BonnMu F2 stocks are deposited in the Maize Genetics and Genomics Database (MaizeGDB), with seeds available to the community. Here, we discuss the creation, expansion, and application of the BonnMu resource for identifying and characterizing mutations induced by Mu transposons, which represents a useful tool for functional genomics studies in maize.

Clinically Relevant Genes Identified in Cerebral Palsy Cohorts Following Evaluation of the Clinical Description and Phenotype: A Systematic Review.

A growing number of genes have been identified in individuals with cerebral palsy (CP); however, many of these studies have poor compliance with the cerebral palsy clinical description. This systematic review aimed to assess the quality of the cerebral palsy clinical description/phenotype in cerebral palsy genetic studies published between 2010 and 2024 and report clinically relevant genes based on the quality of the cerebral palsy phenotype. An expert panel developed 6 criteria to review the reported cerebral palsy phenotype/description for each included study. Clinically relevant genes were extracted from each study and stratified into 2 tiers based on the quality. Eighteen studies were included. There was high confidence in the reported cerebral palsy description/phenotype from 8 studies. Of the initial 373 clinically relevant genes, 85 were tier II genes. Individual cerebral palsy motor disorder and phenotype data were absent for 349 of these individuals, limiting further analysis. The tier I gene list was composed of 6 genes: ATL1, COL4A1, GNAO1, KIF1A, SPAST, and TUBA1A. Bilateral spasticity was the most common motor disorder reported in individuals with variants in all 6 genes, and most individuals had accompanying conditions. Prioritizing the accurate reporting of motor and nonmotor phenotypes is crucial for future cerebral palsy genetic studies to further understand the underlying neurobiology.

Endothelium Piezo1 deletion alleviates experimental varicose veins by attenuating perivenous inflammation.

Previous large-scale genetic studies have prioritized the causal genes piezo type mechanosensitive ion channel component 1 (PIEZO1) and castor zinc finger 1 (CASZ1) associated with varicose veins (VVs). This study aims to evaluate their roles in both clinical and experimental VVs. In this study, we investigated abundance of PIEZO1 and CASZ1 in both varicose and normal veins from the same patients. Yoda1 (a selective PIEZO1 agonist, 2.6mg/kg/day) or vehicle was administered intraperitoneally for 3weeks to evaluate the effect of PIEZO1 activation on experimental VVs. Subsequently, endothelial Piezo1 deletion mice (Piezo1iΔEC mice) were generated to explored the role of endothelial PIEZO1 on VVs. Laser speckle imaging, flow cytometry, cell tracing with Evans blue or rhodamine-6G, and histopathological staining were utilized to evaluate the pathophysiology of VVs. Our results showed that mRNA expression of PIEZO1, but not CASZ1, was abundant and increased in clinical VVs. The Piezo1tP1-td mice revealed endothelium-specific expression of PIEZO1 in mice veins. By establishing iliac vein ligation-induced VVs in mice, Yoda1 exacerbated experimental VVs with increased inflammatory cell infiltration. Subsequently, endothelial Piezo1 deletion (Piezo1iΔEC mice) alleviated experimental VVs and vascular remodeling by directly reducing vascular permeability and leukocyte-endothelium interactions compared to the control (Piezo1fl/fl mice). PIEZO1 is highly expressed in clinical VVs, meanwhile, activation or inhibition of PIEZO1 exerts a remarkable effect on experimental VVs. Furthermore, Piezo1 may constitute a potential therapeutic approach for the medical treatment of VVs.