Phenotypic Variation Research Articles

Habitat-specific allocations of elements in Atriplex lentiformis seeds indicate adaptation to metal toxicity.

Self-sustaining vegetation in metal-contaminated areas is essential for rebuilding ecological resilience and community stability in degraded lands. Metal-tolerant plants originating from contaminated post-mining areas may hold the key to successful plant establishment and growth. Yet, little is known about the impact of metal toxicity on reproductive strategies, metal accumulation, and allocation patterns at the seed stage. Our research focused on the metal tolerant Atriplex lentiformis. Specifically, we examined the effects of toxic metal(loid) concentration in soils on variability in its reproductive strategies, including germination patterns, elemental uptake, and allocation within the seeds. We employed advanced imaging techniques like synchrotron X-ray fluorescence microscopy (2D scans and 3D tomograms) combined with inductively coupled plasma mass spectrometry to reveal significant differences in metal(loid) concentration and distribution within the seed structures of A. lentiformis from contrasting habitats. Exclusive Zn hotspots of high concentrations were found in the seeds of the metallicolous accession, primarily in the sensitive tissues of shoot apical meristems and root zones of the seed embryos. Our findings offer novel insights into phenotypic variability and metal tolerance and accumulation in plants from extreme environments. This knowledge can be applied to enhance plant survival and performance in land restoration efforts.

Comparison of machine learning methods for genomic prediction of selected Arabidopsis thaliana traits.

We present a comparison of machine learning methods for the prediction of four quantitative traits in Arabidopsis thaliana. High prediction accuracies were achieved on individuals grown under standardized laboratory conditions from the 1001 Arabidopsis Genomes Project. An existing body of evidence suggests that linear models may be impeded by their inability to make use of non-additive effects to explain phenotypic variation at the population level. The results presented here use a nested cross-validation approach to confirm that some machine learning methods have the ability to statistically outperform linear prediction models, with the optimal model dependent on availability of training data and genetic architecture of the trait in question. Linear models were competitive in their performance as per previous work, though the neural network class of predictors was observed to be the most accurate and robust for traits with high heritability. The extent to which non-linear models exploit interaction effects will require further investigation of the causal pathways that lay behind their predictions. Future work utilizing more traits and larger sample sizes, combined with an improved understanding of their respective genetic architectures, may lead to improvements in prediction accuracy.

Endocrinological features and epileptic encephalopathy in COX deficiency due to SCO1 mutations: case series and review of literature.

Cytochrome C oxidase (COX) is the fourth component of the respiratory chain and is located within the internal membrane of mitochondria. COX deficiency causes an inherited mitochondrial disease with significant genetic and phenotypic heterogeneity. Four clinical subtypes have been identified, each with distinct phenotypes and genetic variants. Mitochondrial complex IV deficiency nuclear type 4 (MC4DN4) is a form of COX deficiency associated with pathogenic variants in the SCO1 gene. We describe three patients with MC4DN4 with developmental and epileptic encephalopathy (DEE), hypopituitarism, and SCO1 pathogenic variants. These patients' phenotypes considerably differ from previously reported MC4DN4 phenotypes as they associate DEE with progressive hypopituitarism and survival beyond the first months after birth. Pituitary deficiency in these patients progressively worsened and mainly involved growth hormone secretion and thyroid function. Our findings expand knowledge of phenotypic variability in MC4DN4 and suggest that SCO1 is a candidate gene for genetic hypopituitarism and DEE. Our paper describes three patients affected by MC4DN4 with hypopituitarism and developmental and epileptic encephalopathy (DEE), two features that have never been associated with this condition. In addition, we reviewed the clinical features of all previous cases of MC4DN4 to give the other clinicians a wide picture of the clinical phenotype of this genetic disease. We hope that the publication of our data may help others to identify this disease and consider the chance to analyze the SCO1 gene in cases of DEE associated with pituitary dysfunction. Our article contributes to expanding the spectrum of genetic hypopituitarism and proposes a model to explain an association between this condition, mitochondrial anomalies, and neurodevelopmental defects.

Contribution of homoeologous exchange to domestication of polyploid Brassica

BackgroundPolyploidy is widely recognized as a significant evolutionary force in the plant kingdom, contributing to the diversification of plants. One of the notable features of allopolyploidy is the occurrence of homoeologous exchange (HE) events between the subgenomes, causing changes in genomic composition, gene expression, and phenotypic variations. However, the role of HE in plant adaptation and domestication remains unclear.ResultsHere we analyze the whole-genome resequencing data from Brassica napus accessions representing the different morphotypes and ecotypes, to investigate the role of HE in domestication. Our findings demonstrate frequent occurrence of HEs in Brassica napus, with substantial HE patterns shared across populations, indicating their potential role in promoting crop domestication. HE events are asymmetric, with the A genome more frequently replacing C genome segments. These events show a preference for specific genomic regions and vary among populations. We also identify candidate genes in HE regions specific to certain populations, which likely contribute to flowering-time diversification across diverse morphotypes and ecotypes. In addition, we assemble a new genome of a swede accession, confirming the HE signals on the genome and their potential involvement in root tuber development. By analyzing HE in another allopolyploid species, Brassica juncea, we characterize a potential broader role of HE in allopolyploid crop domestication.ConclusionsOur results provide novel insights into the domestication of polyploid Brassica species and highlight homoeologous exchange as a crucial mechanism for generating variations that are selected for crop improvement in polyploid species.

Genome‐Wide Association Studies Predicted Drought Stress Occuring at Anthesis and Post‐Anthesis Stages in Novel Diverse Germplasm of Bread Wheat (Triticum aestivum)

ABSTRACTThis study employed genome‐wide association studies (GWAS) to identify the crucial marker–trait associations (MTAs) for agronomic and physiological traits in bread wheat grown under full irrigation and 40% reduced irrigation. One hundred twenty‐four genotypes derived from three‐way crosses of landraces and synthetic bread wheat were evaluated for 2 years in the field conditions of CIMMYT Obregon, Mexico. Irrigation was not provided at anthesis and post‐anthesis stage for the drought treatment, and data of 12 traits were recorded. Most of the traits were reduced significantly under drought conditions except for vigour, wax and spike length (SL); genotypes were significantly different for the eight traits except for days to heading (DTH), number of grains spike−1 (NGS), normalized difference in vegetation index (NDVI) and canopy temperature depression (CTD); and differences were also significant for five traits between the years. Moreover, GY was significantly and negatively correlated with wax and CTD. Our GWAS results indicated 117 significant (p ≤ 0.001) MTAs distributed on all the wheat chromosomes except chromosomes 4B and 4D explaining 10%–21.5% of the phenotypic variation of the corresponding traits. Moreover, 22 MTAs were recorded for grain yield and explaining the phenotypic variations up to 14.7% with one common association under both irrigated and drought conditions. Additionally, we also identified the associations for NDVI, CTD and SL at chromosome 1B, suggesting that genotypes are sustaining superior grain yield through better values of traits like NDVI, CTD, and SL under the challenging conditions of anthesis and post‐anthesis drought stress.

Single-cell RNA sequencing of nc886, a non-coding RNA transcribed by RNA polymerase III, with a primer spike-in strategy.

Single-cell RNA sequencing (scRNA-seq) has emerged as a versatile tool in biology, enabling comprehensive genomic-level characterization of individual cells. Currently, most scRNA-seq methods generate barcoded cDNAs by capturing the polyA tails of mRNAs, which exclude many non-coding RNAs (ncRNAs), especially those transcribed by RNA polymerase III (Pol III). Although previously thought to be expressed constitutively, Pol III-transcribed ncRNAs are expressed variably in healthy and disease states and play important roles therein, necessitating their profiling at the single-cell level. In this study, we developed a measurement protocol for nc886 as a model case and initial step for scRNA-seq for Pol III-transcribed ncRNAs. Specifically, we spiked in an oligo-tagged nc886-specific primer during the polyA tail capture process for the 5'scRNA-seq. We then produced sequencing libraries for standard 5' gene expression and oligo-tagged nc886 separately, to accommodate different cDNA sizes and ensure undisturbed transcriptome analysis. We applied this protocol in three cell lines that express high, low, and zero levels of nc886. Our results show that the identification of oligo tags exhibited limited target specificity, and sequencing reads of nc886 enabled the correction of non-specific priming. These findings suggest that gene-specific primers (GSPs) can be employed to capture RNAs lacking a polyA tail, with subsequent sequence verification ensuring accurate gene expression counting. Moreover, we embarked on an analysis of differentially expressed genes in cell line sub-clusters with differential nc886 expression, demonstrating variations in gene expression phenotypes. Collectively, the primer spike-in strategy allows combined analysis of ncRNAs and gene expression phenotype.

Elucidation of the genetic architecture of water absorption capacity in hard winter wheat through genome wide association study.

Water absorption capacity (WAC) influences various aspects of bread making, such as loaf volume, bread yield, and shelf life. Despite its importance in the baking process and end-product quality, its genetic determinants are less explored. To address this limitation, a genome-wide association study was conducted on 337 hard wheat (Triticum aestivum L.) genotypes evaluated over 5 years in multi-environmental trials. Phenotyping was done using the solvent retention capacity (SRC) test with water (SRC-water), sucrose (SRC-sucrose), lactic acid (SRC-lactic acid), and sodium carbonate (SRC-carbonate) as solvents. Individuals were genotyped using genotyping-by-sequencing to detect single nucleotide polymorphisms across the wheat genome. To detect the genomic regions that underline the SRCs and gluten performance index (GPI), a genome-wide association study was performed using six multi-locus models using the mrMLM package in R. Adjusted means for SRC-water ranged from 54.1% to 66.5%, while SRC-carbonate exhibited a narrow range from 84.9% to 93.9%. Moderate to high genomic heritability values were observed for SRCs and GPI, ranging from h2=0.61 to 0.88. The genome-wide association study identified a total of 42 quantitative trait nucleotides (QTNs), of which five explained over 10% of the phenotypic variation (R2 ≥ 10%). Most of the QTNs were detected on chromosomes 1A, 1B, 3B, and 5B. Few QTNs, such as S1A_5190318, S1B_3282665, S4D_472908721, and S7A_37433960, were located near gliadin, glutenin starch synthesis, and galactosyltransferase genes. Overall, these results show WAC to be under polygenic genetic control, with genes involved in the synthesis of key flour components influencing overall water absorption.

Epigenetic gene regulation in plants and its potential applications in crop improvement.

DNA methylation, also known as 5-methylcytosine, is an epigenetic modification that has crucial functions in plant growth, development and adaptation. The cellular DNA methylation level is tightly regulated by the combined action of DNA methyltransferases and demethylases. Protein complexes involved in the targeting and interpretation of DNA methylation have been identified, revealing intriguing roles of methyl-DNA binding proteins and molecular chaperones. Structural studies and in vitro reconstituted enzymatic systems have provided mechanistic insights into RNA-directed DNA methylation, the main pathway catalysing de novo methylation in plants. A better understanding of the regulatory mechanisms will enable locus-specific manipulation of the DNA methylation status. CRISPR-dCas9-based epigenome editing tools are being developed for this goal. Given that DNA methylation patterns can be stably transmitted through meiosis, and that large phenotypic variations can be contributed by epimutations, epigenome editing holds great promise in crop breeding by creating additional phenotypic variability on the same genetic material.

Plasticity in older infants' perception of phonetic contrasts: The role of selective attention in context.

Developmental plasticity refers to conditions and circumstances that increase phenotypic variability. In infancy, plasticity expands and contracts depending on domains of functioning, developmental history, and timing. In terms of language processing, infants attend to and discriminate both native and non-native phonetic contrasts, but selectively attune to their native phonemes by the end of the first postnatal year. However, relevant studies have excluded factors regarded as promoters of attention such as infant-directed (ID) speech, synchronous multimodal presentations, and female speakers. Here we investigated whether English-learning 11-month-olds would discriminate a non-native phonetic contrast while manipulating these factors. Results showed significant discrimination of the non-native contrast, regardless of speech register, provided that they were presented by a dynamic female speaker. Interestingly, when a static object or a dynamic male ID speaker replaced the female, no significant discrimination was found. These results show infants to be capable of discriminating non-native phonetic contrasts in an enhanced context at an age when they have been characterized as not being able to do so. Synchronized, multimodal information from female speakers allowed infants to perceive difficult non-native phonemes, highlighting the importance of an ecologically valid context for studying speech perception and language learning in early development.

Clinical, Histopathologic, and Genetic Features of Patients With Myofibrillary and Distal Myopathies: Experience From the Italian Network.

The diagnostic process for myofibrillar myopathies (MFM) and distal myopathies (DM) is particularly complex because of the large number of causative genes, the existence of still molecularly undefined disease entities, and the overlapping features between the 2 categories. This study aimed to characterize a large cohort of patients affected by MFM and DM and identify the most important diagnostic and prognostic aspects of these diseases. Patients with either a myopathological diagnosis of MFM or a clinical diagnosis of DM were included in this retrospective multicentric national study. Demographic, genetic, clinical, and histopathologic data of anonymized patients were collected from the neuromuscular centers of the Italian Association of Myology network. Data regarding 132 patients with MFM (mean age 57.0 ± 15.8 years, 49% female) and 298 patients with DM (mean age 50.7 ± 15.9 years, 40% female) were gathered from 20 neuromuscular centers. 69 patients fulfilled the criteria for both groups (distal myopathies with myofibrillar pathology, DM-MP). Molecular confirmation was achieved in 63% of the patients. Fifty-two percent of the patients with MFM carried pathogenic variants in either DES (n = 30), MYOT (n = 20), or DNAJB6 (n = 18), which were also the most frequent disease-causing genes in DM-MP, while GNE (n = 44) and MYH7 (n = 23) were the genes most commonly carrying pathogenic variants in DM. The mean age at onset varied from <25 years in patients with causative variants in MYH7 and DYSF to 59 years in patients with myotilinopathies. Cardiac involvement was reported in 29% of patients with MFM and 16% of patients with DM, with DES and MYH7 variants significantly associated with the development of cardiomyopathy. Respiratory impairment was more prevalent in patients with TTN and DES variants and rare in other disorders such as GNE myopathy and dysferlinopathies, which were instead associated, together with DNAJB6-related and PLIN4-related myopathies, with the risk of losing ambulation during the disease course. The Italian cohort of patients with MFM and DM recapitulates the phenotypic heterogeneity and the partial overlap between the 2 groups. However, in relative contrast to the encountered phenotypic variability, only 5 genes accounted for most of the molecular diagnoses. Specific genetic entities are associated with significantly increased risk of developing cardiorespiratory complications or loss of ambulation, which has relevant prognostic implications.

Systematic discovery of gene-environment interactions underlying the human plasma proteome in UK Biobank

Understanding how gene-environment interactions (GEIs) influence the circulating proteome could aid in biomarker discovery and validation. The presence of GEIs can be inferred from single nucleotide polymorphisms that associate with phenotypic variability - termed variance quantitative trait loci (vQTLs). Here, vQTL association studies are performed on plasma levels of 1463 proteins in 52,363 UK Biobank participants. A set of 677 independent vQTLs are identified across 568 proteins. They include 67 variants that lack conventional additive main effects on protein levels. Over 1100 GEIs are identified between 101 proteins and 153 environmental exposures. GEI analyses uncover possible mechanisms that explain why 13/67 vQTL-only sites lack corresponding main effects. Additional analyses also highlight how age, sex, epistatic interactions and statistical artefacts may underscore associations between genetic variation and variance heterogeneity. This study establishes the most comprehensive database yet of vQTLs and GEIs for the human proteome.

Genome-wide copy number variation regions in indigenous (Bos indicus) cattle breeds of Tamil Nadu, India.

Identification of large scale structural polymorphisms (Copy number variations) of more than 50 bp between the individuals of a species would help in knowing genetic diversity, phenotypic variability, adaptability to tropical environment and disease resistance. Read depth-based method implemented in CNVnator was used for calling copy number variant regions on sequenced data obtained from WGS from 15 pooled samples belonging to five draught cattle breeds of Tamil Nadu. A total of 11,605 CNV regions (CNVRs) were observed covering a genome size of 18.63 percent. Among these, 11,459 were restricted to autosomes, consisting of 11,013 deletions, 353 duplications and 93 complex events. These CNVRs were annotated to 4,989 candidate genes. A total of 8,291 numbers of CNVRs were shared among the five cattle breeds as also supported by PCA and STRUCTURE analyses and 1,172 CNVRs were breed-specific. Four out of five selected breed-specific CNVRs were validated using real-time PCR. Genes with CNVRs are related to milk production (BTN1A1, ABCA1 and LAP3), disease resistance (TLR4 and DNAH8), adaptability (SOD1, CAST and SMARCAL1), growth (EGFR, NKAIN3), reproduction (BRWD1 and PDE6D), meat and carcass traits (MAP3K5 and NCAM1) and exterior (ATRN and MITF) traits. Gene enrichment analysis based on the gene list retrieved from the CNVRs disclosed over-represented terms (p<0.01) associated with milk fat production. NETWORK analysis had identified 13 putative candidate genes involved in milk fat percentage, milk fat yield, lactation persistency, milk yield, heat tolerance, calving ease, growth and conformation traits. The genome-wide CNVRs identified in the present study produced genome-wide partial CNV map in indigenous cattle breeds of Tamil Nadu.

GallOnt: An ontology for plant gall phenotypes.

Galls are novel plant structures that develop in response to select biotic stressors. These structures, extended phenotypes of the inducer, usually serve to protect and feed the inducer or its progeny. This life history strategy has evolved dozens of times, and tens of thousands of species - including many bacteria, fungi, nematodes, mites and insects - are capable of manipulating plants in this way. The variation in gall phenotypes is extraordinary across species but usually predictable for each species of inducer. We introduce here a new ontology, GallOnt, that facilitates consistent descriptions and the semantic representation of and reasoning over plant gall phenotype data. GallOnt was largely developed from ontologies in the Open Biological and Biomedical Ontology (OBO) Foundry and stands to connect plant gall phenotypes to knowledge derived from model plant systems, including genotype-phenotype and agricultural research. We also introduce the idea of a new gall data standard - Minimum Information for the Description of Galls (MIDG version 0.1) - as a starting point for discussions regarding cecidology best practices.

QTL Mapping and Candidate Gene Analysis for Starch-Related Traits in Tartary Buckwheat (Fagopyrum tataricum (L.) Gaertn).

Starch is the main component that determines the yield and quality of Tartary buckwheat. As a quantitative trait, using quantitative trait locus (QTL) mapping to excavate genes associated with starch-related traits is crucial for understanding the genetic mechanisms involved in starch synthesis and molecular breeding of Tartary buckwheat varieties with high-quality starch. Employing a recombinant inbred line population as research material, this study used QTL mapping to investigate the amylose, amylopectin, and total starch contents across four distinct environments. The results identified a total of 20 QTLs spanning six chromosomes, which explained 4.07% to 14.41% of the phenotypic variation. One major QTL cluster containing three stable QTLs governing both amylose and amylopectin content, qClu-4-1, was identified and located in the physical interval of 39.85-43.34 Mbp on chromosome Ft4. Within this cluster, we predicted 239 candidate genes and analyzed their SNP/InDel mutations, expression patterns, and enriched KEGG pathways. Ultimately, five key candidate genes, namely FtPinG0004897100.01, FtPinG0002636200.01, FtPinG0009329200.01, FtPinG0007371600.01, and FtPinG0005109900.01, were highlighted, which are potentially involved in starch synthesis and regulation, paving the way for further investigative studies. This study, for the first time, utilized QTL mapping to detect major QTLs controlling amylose, amylopectin, and total starch contents in Tartary buckwheat. The QTLs and candidate genes would provide valuable insights into the genetic mechanisms underlying starch synthesis and improving starch-related traits of Tartary buckwheat.

Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR)- the new lacunae: a case report

BackgroundMicrocephaly with or without chorioretinopathy, lymphedema, or mental retardation is a rare autosomal dominant disease caused by mutations in KIF11 which disrupt EG5 protein function, impacting the development and maintenance of retinal and lymphatic structures due to its expression in the retinal photoreceptor cilia. The primary ocular finding in MCLMR is chorioretinopathy. Additional features can include microphthalmia, angle-closure glaucoma, persistent hyperplastic primary vitreous, cataract, pseudo-coloboma, persistent hyaloid artery, and myopic or hypermetropic astigmatism. The appearance of the chorioretinal lesions as white to pinkish, round, non-elevated atrophic areas devoid of blood vessels resembles the lacunae in Aicardy syndrome. Due to the lack of systematic description of the lesions and significant phenotypical variability, there is an impending need for a detailed report of each case.Case presentationA child with microcephaly detected in the third trimester of gestation began her following in the ophthalmology department due to a non-visually significant cataract. Shortly after, she developed nystagmus and large-angle alternating esotropia with cross-fixation. Her fundus initially showed a pallid optic disc and pigmentary changes, developing thereafter retinal lacunae and a retinal fold. Her differential diagnosis accompanied the dynamic changes in her fundus, which included congenital infections, Leber´s Congenital Amaurosis and Aicardy syndrome. At 19 months old, genetic testing identified a heterozygous mutation (c.1159 C > T, p.Arg387*) in the KIF11 gene. The patient underwent bilateral medial rectus muscle recession surgery at 2 years old for persistent esotropia, with significant improvement. Refraction revealed a hyperopic astigmatism in both eyes (+ 0.25 -2.50 × 180 OD and + 0.75 -2.00 × 170 OS). She continues to require right eye patching for 2 hours daily.ConclusionsThis case report expands the phenotypic spectrum of MCLMR by demonstrating a unique combination of retinal features which sheds new light on differential diagnosis from Aicardy syndrome. Our findings emphasize the significant phenotypic variability associated with MCLMR, particularly regarding ocular involvement. This underscores the importance of detailed clinical evaluation and comprehensive reporting of cases to improve our understanding of the disease spectrum and genotype-phenotype correlations.

Identification and Mapping of QTLs for Adult Plant Resistance in Wheat Line XK502.

Stripe rust is a serious wheat disease occurring worldwide. At present, the most effective way to control it is to grow resistant cultivars. In this study, a population of 221 recombinant inbred lines (RILs) derived via single-seed descent from a hybrid of a susceptible wheat line, SY95-71, and a resistant line, XK502, was tested in three crop seasons from 2022 to 2024 in five environments. A genetic linkage map was constructed using 12,577 single-nucleotide polymorphisms (SNPs). Based on the phenotypic data of infection severity and the linkage map, five quantitative trait loci (QTL) for adult plant resistance (APR) were detected using the inclusive composite interval mapping (ICIM) method. These five loci are QYrxk502.swust-1BL, QYrxk502.swust-2BL, QYrxk502.swust-3AS, QYrxk502.swust-3BS, and QYrxk502.swust-7BS, explaining 5.67-19.64%, 9.63-36.74%, 9.58-11.30%, 9.76-23.98%, and 8.02-12.41% of the phenotypic variation, respectively. All these QTL originated from the resistant parent XK502. By comparison with the locations of known stripe rust resistance genes, three of the detected QTL, QYrxk502.swust-3AS, QYrxk502.swust-3BS, and QYrxk502.swust-7BS, may harbor new, unidentified genes. From among the tested RILs, 16 lines were selected with good field stripe rust resistance and acceptable agronomic traits for inclusion in breeding programs.

Genome-Wide Association Study of Conformation Traits in Brazilian Holstein Cattle.

The linear conformation of animals exerts an influence on health, reproduction, production, and welfare, in addition to longevity, which directly affects the profitability of milk-producing farms. The objectives of this study were (1) to perform genome-wide association studies (GWASs) of conformation traits, namely the Rump, Feet and Legs, Mammary System, Dairy Strength, and Final Classification traits, and (2) to identify genes and related pathways involved in physiological processes associated with conformation traits in Brazilian Holstein cattle. Phenotypic and genotypic data from 2339 Holstein animals distributed across the states of Rio Grande do Sul, Paraná, São Paulo, and Minas Gerais were used. The genotypic data were obtained with a 100 K SNP marker panel. The single-step genome-wide association study (ssGWAS) method was employed in the analyses. Genes close to a significant SNP were identified in an interval of 100 kb up- and downstream using the Ensembl database available in the BioMart tool. The DAVID database was used to identify the main metabolic pathways and the STRING program was employed to create the gene regulatory network. In total, 36 significant SNPs were found on 15 chromosomes; 27 of these SNPs were linked to genes that may influence the traits studied. Fourteen genes most closely related to the studied traits were identified, as well as four genes that showed interactions in important metabolic pathways such as myogenesis, adipogenesis, and angiogenesis. Among the total genes, four were associated with myogenesis (TMOD2, TMOD3, CCND2, and CTBP2), three with angiogenesis (FGF23, FGF1, and SCG3), and four with adipogenesis and body size and development (C5H12orf4, CCND2, EMILIN1, and FGF6). These results contribute to a better understanding of the biological mechanisms underlying phenotypic variability in conformation traits in Brazilian Holstein cattle.

Genome wide detection of CNV and their association with body size in Danzhou chickens

Copy number variation (CNV) is a crucial component of genetic diversity in the genome, serving as the foundation for the genetic architecture and phenotypic variability of complex traits. In this study, we examined CNVs in the Danzhou (DZ) chicken, an indigenous breed exclusive to Hainan Province, China. By employing whole-genome resequencing data from 200 DZ chickens, we conducted a comprehensive genome-wide analysis of CNVs using CNVpytor and performed CNV-based genome-wide association studies (GWAS) on six body size traits, including body slope length (BSL), keel length (KeL), tibial length (TiL), tibial circumference (TiC), chest width (ChW), and chest depth (ChD) utilizing linear mixed model methods considering a genomic relationship matrix. We identified a total of 144,265 autosomal CNVs among the 200 individuals, comprising 67,818 deletions and 76,447 duplications. After merging these variants together, we obtained 4,824 distinct copy number variant regions, which accounted for approximately 20% of the chicken autosomal genome. Furthermore, we discovered several significantly associated CNV segments with body size traits located proximal to genes such as IHH, WNT6, WNT10A, LPR4, FZD2, WNT7B, and GNAS that have been extensively implicated in skeletal development and growth processes. These findings enhance our understanding of CNVs in chickens and their potential impact on body size traits by revealing candidate genes involved in the regulation of these traits. This establishes a solid framework for future studies and may prove particularly beneficial for exploring genetic structural variation in chickens.

Cross-site reproducibility of human cortical organoids reveals consistent cell type composition and architecture

While guided human cortical organoid (hCO) protocols reproducibly generate cortical cell types at one site, variability in hCO phenotypes across sites using a harmonized protocol has not yet been evaluated. To determine the cross-site reproducibility of hCO differentiation, three independent research groups assayed hCOs in multiple differentiation replicates from one induced pluripotent stem cell (iPSC) line using a harmonized miniaturized spinning bioreactor protocol across 3months. hCOs were mostly cortical progenitor and neuronal cell types in reproducible proportions that were consistently organized in cortical wall-like buds. Cross-site differences were detected in hCO size and expression of metabolism and cellular stress genes. Variability in hCO phenotypes correlated with stem cell gene expression prior to differentiation and technical factors associated with seeding, suggesting iPSC quality and treatment are important for differentiation outcomes. Cross-site reproducibility of hCO cell type proportions and organization encourages future prospective meta-analytic studies modeling neurodevelopmental disorders in hCOs.

Priorities and barriers for research related to primary ciliary dyskinesia.

Despite advances in primary ciliary dyskinesia (PCD) research, many questions remain; diagnosis is complex and no disease-specific therapies exist. Using a mixed-methods approach, we aimed to identify priorities for clinical and epidemiological research and explore barriers to research. To obtain rich, relevant, diverse data, we performed in-depth semi-structured interviews with PCD specialists selected using purposive sampling. We transcribed, coded and analysed interview data using thematic analysis. Based on interview themes that we identified, we developed an anonymous survey and circulated it widely through the BEAT-PCD network. We interviewed 28 participants from 15 countries across different disciplines and expertise levels. The main themes identified as priorities for PCD research were improving diagnosis; understanding prevalence and disease course; phenotypic variability; disease monitoring; treatment strategies; clinical trial end-points; and poorly researched areas. In total, 136 participants (49% paediatric pulmonologists) from 36 countries completed the survey. Most commonly reported barriers for research were low awareness about PCD and difficulties securing funding - in more than one-third of cases, participants reported undertaking predominantly unfunded research. Research questions ranked highest included priorities related to further improving diagnosis, treating PCD, managing upper and lower airway problems, and studying clinical variability and disease prognosis. We need to overcome barriers of limited funding and low awareness and promote collaborations between centres, disciplines, experts and patients to address identified PCD priorities effectively. Our results contribute to the ongoing efforts of guiding the use of existing limited research resources and setting up a roadmap for future research activities.