Nucleotide Diversity Research Articles

HOXA7 Expression Is an Independent Prognostic Biomarker in Esophageal Squamous Cell Carcinoma

Background/Objectives: Homeobox (HOX) genes encode conserved transcription factors essential for tissue and organ development and cellular differentiation. In humans, these genes are organized into four clusters: HOXA, HOXB, HOXC, and HOXD. While HOX genes have been extensively studied in cancer biology, their roles in esophageal squamous cell carcinoma (ESCC) remain poorly understood. Given the increasing incidence and high mortality rate of ESCC, exploring the molecular drivers of this tumor is urgent. Methods: Therefore, this study investigated the mutational landscape and expression profiles of HOX genes in ESCC and their differentially expressed targets using ESCC data from The Cancer Genome Atlas (TCGA) and two independent transcriptome datasets. Results: We found that copy number alterations and single nucleotide variations were rare, while seven HOX genes (HOXA2, HOXA7, HOXB13, HOXC9, HOXC10, HOXC13, and HOXD10) were significantly differentially expressed in ESCC compared to paired non-malignant mucosa. Further analysis identified 776 potential HOX target genes differentially expressed in ESCC, many of which are involved in critical cancer pathways such as PI3K-AKT, cell cycle regulation, and epithelial–mesenchymal transition (EMT). The HOXA7 overexpression was associated with poor overall survival rates in ESCC. This finding opens new possibilities for targeted therapies, offering hope for improved patient outcomes. Conclusions: Thus, this study underscored the pivotal role of HOX gene dysregulation in ESCC and classified HOXA7 as a potential prognostic biomarker in this tumor.

Combining Morphological and Molecular Tools Can Enhance Tick Species Identification for Improved Tick-Borne Disease Surveillance Among Pastoral Communities in Kenya.

Background: Ticks are ecto-parasites of domestic animals, rodents, and wildlife living for periods at a time on one or more vertebrate hosts. They are important vectors of viral, bacterial, or parasitic diseases in livestock and humans. Crimean-Congo haemorrhagic fever virus and the spotted fever rickettsiae are some of the tick-borne diseases of public health importance reported in Kenya. Their distribution and public health risks among communities, especially pastoralists, remain poorly characterized due to limited surveillance, affected partly by inadequate capacity for tick identification arising from a limited number of skilled taxonomists. Materials and Methods: The aim of this survey was to identify tick species currently circulating in different livestock hosts in northern Kenya. Ticks were sampled from cattle, sheep, goats, and camels in Turkana, Isiolo, Baringo, and West Pokot counties, and differential identification was carried out using morphological identification keys followed by molecular characterization based on the cytochrome c oxidase I gene (cox1). Haplotypes were determined using the DnaSP v6 software and phylogenetic relationships inferred using the maximum likelihood algorithm. Results: A total of 12,206 ticks were collected, from Turkana (45.4%), Isiolo (23.1%), Baringo (22.7%), and West Pokot (8.8%) counties in Kenya. Ten species were confirmed by molecular analysis; H. rufipes, H. impeltatum, H. dromedarii, R. pravus, R. camicasi, R. pulchellus, R. evertsi evertsi, A. variegatum, A. gemma, and A. lepidum. There was no disparity in the morphological and molecular identification of Amblyomma species. However, molecular analysis provided insight into the complexity of morphological identification especially among Hyalomma and Rhipicephalus species. High haplotype diversities (0.857-1.000) and low nucleotide diversities (0.00719-0.06319) were observed in all the tick samples tested. Conclusion: The findings highlight the diversity of tick species in dry pastoral ecologies in Kenya and the importance of confirming morphological identification by molecular analysis thus contributing to accurate mapping of tick-borne disease distribution and risk.

Genetic analyses of Anisakis pegreffii (Nematoda: Anisakidae) from the East Asian finless porpoise Neophocaena asiaeorientalis sunameri (Cetacea: Phocoenidae) in Korean waters

The East Asian finless porpoise, Neophocaena asiaeorientalis sunameri, is an endangered species that inhabits the coastal marine environments of East Asia. In the present study, we investigated the overall infection status of anisakid nematodes in East Asian finless porpoises from three sea sectors off the Korean Peninsula. The genetic diversity and population genetic structure of the identified nematode species were evaluated. The prevalence of all stages of anisakid nematodes collected from the stomach was 57.55% (61 among the 106 porpoises examined), and 16 of the hosts were found to have adult worms. The mean number of infected adults was 211 (± 419.54, 5–1455 per host). Only one species of anisakids, Anisakis pegreffii, was identified from randomly selected worms by molecular approaches. Analysis of the mitochondrial (mt) cox2 partial gene in 50 newly generated sequences of A. pegreffii revealed 24 haplotypes, including 14 new haplotypes. We observed below-average levels of nucleotide diversity and haplotype diversity compared to other seas around the world. The mtDNA cox2 haplotypes of the species in the three Korean sea areas showed no genetic structure, suggesting well-connected gene flow within these areas. This study represents the first record of a definitive host of A. pegreffii in Korean waters, providing important information regarding anisakids genetic diversity in the cetacean species inhabiting limited regions.

Structured, Inbred and Plastic: the Genome and Population Genetics of the weed False cleavers (Galium spurium)

Abstract False cleavers (Galium spurium L.) is an aggressive weed from the Rubiaceae. Here we assemble a chromosome scale draft of its genome, laying the foundations for determining the genetic basis of auxinic herbicide resistance and for systematic research into its polyphyletic genus. We use the genome to examine the population genetics in material from the Canadian Prairies and, in concert with a common greenhouse experiment, to examine whether the phenotypic variation observed in the field results primarily from genetic or environmental factors. The genome assembly covers approximately 85% of G. spurium’s expected 360Mbp genome size with 94% of BUSCO genes complete and most single copy (89%). Approximately 37% of the genome is repetitive elements and 35,540 genes were annotated using RNA-Seq data, including 100 homologs for genes involved or, potentially involved in, herbicide resistance. The genome shows strong synteny with other members of the Rubiaceae including smooth bedstraw (Cruciata laevipes Opiz) and robusta coffee [Coffea canephora (Pierre ex Froehner]. Double digested RADseq data for the 19 populations from the Canadian Prairies indicated that G. spurium has high levels of population structure (FST = 0.54) and inbreeding (FIS =0.86) with low levels of hetrozygosity (HO = 0.02) and nucleotide diversity (π = 0.0003). Variation in flowering time and seed weight largely overlapped among populations grown in the greenhouse. A redundancy analysis investigating genotype-phenotype associations showed few associations between SNP variation and these characteristics. In contrast, the majority of SNPs under selection were associated with mericarp hook density. This suggests that for most traits, environmental variation rather than genetic variation likely underlies phenotypic differences observed in the field. Several genes of interest including several homologs involved in the assembly of the Skp1-Culliun-F-Box IR1/AFB E3 ubiquitin ligase complex (e.g. CAND1, ECR1) are located in areas of the genome with evidence of selection and are targets for further investigation.

Using intrahost single nucleotide variant data to predict SARS-CoV-2 detection cycle threshold values.

Over the last four years, each successive wave of the COVID-19 pandemic has been caused by variants with mutations that improve the transmissibility of the virus. Despite this, we still lack tools for predicting clinically important features of the virus. In this study, we show that it is possible to predict the PCR cycle threshold (Ct) values from clinical detection assays using sequence data. Ct values often correspond with patient viral load and the epidemiological trajectory of the pandemic. Using a collection of 36,335 high quality genomes, we built models from SARS-CoV-2 intrahost single nucleotide variant (iSNV) data, computing XGBoost models from the frequencies of A, T, G, C, insertions, and deletions at each position relative to the Wuhan-Hu-1 reference genome. Our best model had an R2 of 0.604 [0.593-0.616, 95% confidence interval] and a Root Mean Square Error (RMSE) of 5.247 [5.156-5.337], demonstrating modest predictive power. Overall, we show that the results are stable relative to an external holdout set of genomes selected from SRA and are robust to patient status and the detection instruments that were used. This study highlights the importance of developing modeling strategies that can be applied to publicly available genome sequence data for use in disease prevention and control.

Complete Chloroplast Genome of Crassula aquatica: Comparative Genomic Analysis and Phylogenetic Relationships

Background/Objectives: Crassula aquatica (L.) Schonl. is a very small annual plant growing along riverbanks. Chloroplast (cp) genomes, crucial for photosynthesis, are highly conserved and play a key role in understanding plant evolution. In this study, we conducted cp genome analysis of C. aquatica, aiming to elucidate its phylogenetic position and structural variations. We analyzed and described the features of the complete cp genome of C. aquatica and conducted comparative analysis with the cp genomes of closely related taxa. Rsults: The cp genome was 144,503 bp in length and exhibited the typical quadripartite structure, consisting of a large single-copy region (LSC; 77,993 bp), a small single-copy region (SSC; 16,784 bp), and two inverted repeats (24,863 bp). The cp genome of C. aquatica comprised 113 unique genes, including 79 protein-coding genes (PCGs), 30 tRNAs, and 4 rRNA genes. Comparative genomic analysis of 13 other Crassula species and six outgroups demonstrated highly conserved gene content and order among Crassula species. However, notable differences were observed, including the complete loss of the rpoC1 intron in C. aquatica and several closely related species, which may serve as a synapomorphic trait supporting the monophyly of the subgenus Disporocarpa. We analyzed the nucleotide diversity among 14 Crassula cp genomes and identified five highly variable regions (pi > 0.08) in the IGS regions. Phylogenetic analysis based on 78 PCGs confirmed the monophyly of Crassula and its division into two subgenera: Crassula and Disporocarpa. Although the phylogenetic tree supported the subgeneric classification system, the sectional classification system requires reassessment. Conclusions: In this study, we conducted a comparative analysis of the cp genome of the genus Crassula. We inferred evolutionary trends within the Crassula cp genome and provided molecular evidence supporting the integration of the genus Tillaea into the genus Crassula. However, as this study does not represent all species within the genus Tillaea, further comprehensive phylogenetic analyses are requrired.

Genetic and Haplotype Diversity of Clarias gariepinus (Burchell 1822) Based on Cytochrome c Oxidase I (COI) Gene

The evaluation of mitochondrial DNA and genetic analysis is helpful for economically significant species. Clarias gariepinus is a critical species in aquaculture. This study investigates the genetic diversity and population differentiation of C. gariepinus from 19 countries using 164 sequences of the mitochondrial DNA’s Cytochrome c oxidase I (COI) gene. The haplotype analysis revealed a total of 17 haplotypes, with a nucleotide diversity (π) of 0.012 and a haplotype diversity (Hd) of 0.87. The results of an AMOVA and fixation index indicated significant genetic variation and structure among the populations. Additionally, neutrality tests and mismatch distribution analysis supported the hypothesis of under-purifying selection in C. gariepinus. The findings suggested that the population did not experience expansion. In conclusion, the genetic analysis highlighted substantial variation among C. gariepinus populations from different locations, providing valuable insights for the global management of this species.

StSNV: a comprehensive resource of SNVs in spatial transcriptome.

Single nucleotide variants (SNVs), as important componentsof genetic variation, affect gene expression, function and phenotype. Mining and summarizing the spatial distribution of SNVs in diseased and normal tissues for a better understanding of their characteristics and potential roles in cell-lineage determination, aging, or disease occurrence is significant. Herein, we have developed a comprehensive spatial mutation resource stSNV (http://bio-bigdata.hrbmu.edu.cn/stSNV/index.jsp), which provides an atlas of spatial SNVs in major diseased and normal tissues of human and mouse. stSNV documents 42202 spatial mutated genes involving 898908 SNVs called from 730067 spots within 450 slices from 19 diseased and 28 normal tissues. Importantly, potential characteristics of SNVs are explored and provided by analyzing the perturbation of the SNVs to gene expression, spatial communication,biological function, region-specific mutated genes, spatial mutant signatures, SNV-cell co-localizationand mutation core region. All these spatial mutation data and in-depth analyses have been integrated into a user-friendly interface, visualized through intuitive tables and various image formats. Flexible tools are developed to explore co-localization among clusters, genes, cell types and SNVs in the same slice. In summary, stSNV as a valuable resourcehelps to dissect intra-tissue genetic heterogeneity and lays the groundwork for understanding the SNVs' biological regulatory mechanisms.

Diversity of the Chicken Growth Hormone Gene and Effects on Growth Desi and Fayoumi Chicken Traits at District Kashmore, Sindh-Pakistan

Chicken growth hormone (cGH) gene, one of the candidate genes for economic traits that control body weight and fat deposition, is associated with regulating both growth-axon patterning and metabolism. The growth hormone gene located on the chromosome 2 it enhances and encodes growth hormones as well as protein which are responsible for regulating of growth and development of body tissues. Growth hormone gene as economically very important because of growth rate, efficiency of feeds, body weight, and also for egg production. It also used for the Genetic Engineering for production of desirable GH- related genes. Genomic DNA from four different chicken breeds were screened for single nucleotide polymorphisms (SNPs) of cGH gene by denaturing high-performance liquid chromatography, as well as sequencing. SNPs and Nucleotide Diversity of the cGH Gene PCR amplification of 700 bp region from each individual from two chicken breeds was performed, which covered partial exons/introns encoding fragments corresponding to the investigated translated peptide. An average of one SNP was found every 86 bp, with a total of eight SNPs discovered. Nine SNPs were in introns, while 4 and one each was in the 5'UTR and 3'UTR respectively of these, five of them (01 from GWAS linkage signals) had significant associations.

Plastid phylogenomics of Robinsonia (Senecioneae; Asteraceae), endemic to the Juan Fernández Islands: insights into structural organization and molecular evolution

BackgroundThe genus Robinsonia DC. (tribe Senecioneae, Asteraceae) endemic to the Juan Fernández Islands in Chile is one of the most conspicuous insular plant groups in the world. Unlike typical herbaceous Asteraceae plants, these plants demonstrate spectacular and unusual rosette tree growth forms as shown by the alpine giant senecios (genus Dendrosenecio, tribe Senecioneae) endemic to the East African mountains. However, monophyly of the genus and phylogenetic relationships among species of Robinsonia as well as their plastome evolution remain elusive. This study aims to explore their phylogeny, species diversification, and molecular evolution based on the complete plastome sequences in the context of adaptive radiation on oceanic islands.ResultsThe insular Robinsonia plastomes are highly conserved in their structures and organization of contents. Five divergence hotspots as potential chloroplast markers and five positively selected coding genes (accD, ndhF, rpoA, ycf1, and ycf2) are identified. Robinsonia plastomes has an overall nucleotide diversity higher than that of the sky island Dendrosenecio, but much lower than herbaceous Senecio. Phylogenetic analysis demonstrates the monophyly of Robinsonia and identifies two major infrageneric lineages. Both Robinsonia and Dendrosenecio are deeply nested within large genus Senecio.ConclusionsWhile plastid genomes of Robinsonia are highly conserved, their sequences strongly demonstrated the monophyly of the genus and inferred robust interspecific relationships, including herbaceous Senecio and woody Dendrosenecio. Different sets of positively selected chloroplast genes, five for Robinsonia and two for Dendrosenecio, may play an important role in the adaptation strategies of these fascinating woody species in insular and continental sky island habitats. Overall phylogenetic positions and sister lineages of Robinsonia and Dendrosenecio require additional study based on broader sampling of Senecio.

Genome Sequencing Identifies 13 Novel Candidate Risk Genes for Autism Spectrum Disorder in a Qatari Cohort

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Despite considerable research efforts, the genetic complexity of ASD remains poorly understood, complicating diagnosis and treatment, especially in the Arab population, with its genetic diversity linked to migration, tribal structures, and high consanguinity. To address the scarcity of ASD genetic data in the Middle East, we conducted genome sequencing (GS) on 50 ASD subjects and their unaffected parents. Our analysis revealed 37 single-nucleotide variants from 36 candidate genes and over 200 CGG repeats in the FMR1 gene in one subject. The identified variants were classified as uncertain, likely pathogenic, or pathogenic based on in-silico algorithms and ACMG criteria. Notably, 52% of the identified variants were homozygous, indicating a recessive genetic architecture to ASD in this population. This finding underscores the significant impact of high consanguinity within the Qatari population, which could be utilized in genetic counseling/screening program in Qatar. We also discovered single nucleotide variants in 13 novel genes not previously associated with ASD: ARSF, BAHD1, CHST7, CUL2, FRMPD3, KCNC4, LFNG, RGS4, RNF133, SCRN2, SLC12A8, USP24, and ZNF746. Our investigation categorized the candidate genes into seven groups, highlighting their roles in cognitive development, including the ubiquitin pathway, transcription factors, solute carriers, kinases, glutamate receptors, chromatin remodelers, and ion channels.

A burden of rare copy number variants in obsessive-compulsive disorder.

Current genetic research on obsessive-compulsive disorder (OCD) supports contributions to risk specifically from common single nucleotide variants (SNVs), along with rare coding SNVs and small insertion-deletions (indels). The contribution to OCD risk from rare copy number variants (CNVs), however, has not been formally assessed at a similar scale. Here we describe an analysis of rare CNVs called from genotype array data in 2248 deeply phenotyped OCD cases and 3608 unaffected controls from Sweden and Norway. Cases carry an elevated burden of CNVs ≥30 kb in size (OR = 1.12, P = 1.77 × 10-3). The excess rate of these CNVs in cases versus controls was around 0.07 (95% CI 0.02-0.11, P = 2.58 × 10-3). This signal was largely driven by CNVs overlapping protein-coding regions (OR = 1.19, P = 3.08 × 10-4), particularly deletions impacting loss-of-function intolerant genes (pLI >0.995, OR = 4.12, P = 2.54 × 10-5). We did not identify any specific locus where CNV burden was associated with OCD case status at genome-wide significance, but we noted non-random recurrence of CNV deletions in cases (permutation P = 2.60 × 10-3). In cases where sufficient clinical data were available (n = 1612) we found that carriers of neurodevelopmental duplications were more likely to have comorbid autism (P < 0.001), and that carriers of deletions overlapping neurodevelopmental genes had lower treatment response (P = 0.02). The results demonstrate a contribution of rare CNVs to OCD risk, and suggest that studies of rare coding variation in OCD would have increased power to identify risk genes if this class of variation were incorporated into formal tests.

Germline Variants in Proto-Oncogenes and Tumor Suppressor Genes in Women with Cervical Cancer

Background/Objectives: Cervical cancer (CC) remains a significant global health challenge, characterized by genetic heterogeneity and a complex molecular landscape, both of which contribute to its pathogenesis. This study aimed to investigate germline variants in proto-oncogenes and tumor suppressor genes in cervical cancer patients, with the objective of clarifying their potential role in disease development. Methods: We utilized a custom next-generation sequencing (NGS) panel targeting 48 genes implicated in oncogenesis. Germline DNA samples from cervical cancer patients were analyzed in order to identify nucleotide sequence alterations. Variants were classified according to pathogenicity and clinical relevance, based on established guidelines. Results: A total of 148 nucleotide variants were detected within the cohort. Of these, 35 variants (23.6%) were classified as benign. In contrast, 105 variants (70.9%) were identified as variants of uncertain significance (VUSs). Moreover, seven pathogenic or likely pathogenic mutations were discovered, along with the polymorphic variant rs1042522 in the TP53 gene, which has been associated with an increased risk of cervical cancer. Conclusions: Our findings contribute to expanding our understanding of the molecular genetic landscape of cervical cancer. They emphasize the potential contribution of rare germline mutations to its development and progression. These results highlight the importance of comprehensive genetic screening in order to improve diagnostic and therapeutic approaches for cervical cancer patients.

Multiple Maternal Lineages of &lt;i&gt;Strauchbufo raddei&lt;/i&gt; (Strauch, 1876) in Mongolia Revealed by Mitochondrial DNA

The Mongolian toad Strauchbufo raddei (Strauch, 1876) is one of widely distributed and dominated amphibian species in eastern Asian, including Mongolia. In this study, we amplified and sequenced a total of 50 samples of S. raddei, from three main regions in its Mongolian distribution range namely, Northern, Eastern, and Gobi regions. Our phylogenetic trees (Bayesian inference; BI and time-calibrated) and network analysis clearly support presence of multiple maternal mitochondrial DNA lineages for S. raddei in Mongolia. As expected, samples from these three regions were clustered separately in BI tree (Bayesian posterior probability (BPP 0.52). In addition, the population specific haplotypes, estimated genetic distances (e.g. uncorrelated p distance; ranged from 1% to 25%) and hierarchical AMOVA suggested relatively strong population genetic structure of S. raddei across Mongolia. Time-calibrated tree and ancestral range analysis showed that the first colonization of S. raddei may have occurred in Northern part of Mongolia approximately 9.63 mya, then dispersed over other parts of the country. Estimated approximate time for crossing event of S. raddei over dry steppe and semi-desert regions in Mongolia was 5.02 – 2.50 mya. Finally, high level of genetic diversity (overall; haplotype diversity, Hd = 0.93; nucleotide diversity, π = 0.011) of S. raddei were observed in Mongolia. Importantly, through this study, we contributed to closing sampling gaps in distribution range of S. raddei in Eastern Asia, which is key to better understanding species history, as well as describing cryptic lineages.

Comparative targeted genome profiling between solid and liquid biopsies in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a proof-of-concept pilot study.

Clinical presentation and genetic profile of gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are highly variable, hampering their management. Sequencing of circulating tumor DNA (ctDNA) from liquid biopsy (LB) has been proposed as a less invasive alternative to solid biopsy (SB). Our aim is to compare the mutational profile (MP) provided by LB with that deriving from SB in GEP-NETs. SB and LB derived simultaneously from 6 GEP-NETs patients. A comparative targeted Next Generation Sequencing (NGS) analysis was performed on DNA from SB and LB to evaluate the mutational status of 11 genes (MEN1, DAXX, ATRX, MUTYH, SETD2, DEPDC5, TSC2, ARID1A, CHECK2, MTOR, PTEN). Patients (M:F =2:1; median age 64 yrs) included 3 with pancreatic and 3 with ileal NETs. NGS detected a median number of 55 variants/sample in SB and 66.5 variants/sample in LB specimens (mutational burden: 0.2-1.9 and 0.3-1.8 mut/Mb, respectively). Missense and nonsense mutations were prevalent in both, mainly represented by C&gt;T transitions. ARID1A, MTOR, and ATRX were consistently mutated in SB and ARID1A, TSC2, MEN1, PTEN, SETD2, and MUTYH were consistently mutated in LB. DAXX mutations were absent in LB. 17 recurrent mutations were shared between SB and LB; in particular, MTOR single nucleotide variants (SNVs) c.G4731A and c.C2997T were shared by 5 out of 6 patients. Hierarchical clustering supported genetic similarity between SB and LB. This pilot study explores the applicability of LB in GEP-NETs MP evaluation. Further studies with larger cohorts are needed to validate LB and to define the clinical impact.

Abundant genetic variation is retained in many laboratory schistosome populations.

Schistosomes are obligately sexual blood flukes that can be maintained in the laboratory using freshwater snails as intermediate and rodents as definitive hosts. The genetic composition of laboratory schistosome populations is poorly understood: whether genetic variation has been purged due to serial inbreeding or retained is unclear. We sequenced 19 - 24 parasites from each of five laboratory Schistosoma mansoni populations and compared their genomes with published exome data from four S. mansoni field populations. We found abundant genomic variation (0.897 - 1.22 million variants) within laboratory populations: these retained on average 49% (π = 3.27e-04 - 8.94e-04) of the nucleotide diversity observed in the four field parasite populations (π = 1.08e-03 - 2.2e-03). However, the pattern of variation was very different in laboratory and field populations. Tajima's D was positive in all laboratory populations except SmBRE, indicative of recent population bottlenecks, but negative in all field populations. Current effective population size estimates of laboratory populations were lower (2 - 258) compared to field populations (3,174 - infinity). The distance between markers at which linkage disequilibrium (LD) decayed to 0.5 was longer in laboratory populations (59 bp - 180 kb) compared to field populations (9 bp - 9.5 kb). SmBRE was the least variable; this parasite also shows low fitness across the lifecycle, consistent with inbreeding depression. The abundant genetic variation present in most laboratory schistosome populations has several important implications: (i) measurement of parasite phenotypes, such as drug resistance, using laboratory parasite populations will determine average values and underestimate trait variation; (ii) genome-wide association studies (GWAS) can be conducted in laboratory schistosome populations by measuring phenotypes and genotypes of individual worms; (iii) genetic drift may lead to divergence in schistosome populations maintained in different laboratories. We conclude that the abundant genetic variation retained within many laboratory schistosome populations can provide valuable, untapped opportunities for schistosome research.

Genetic variants associated with chronic fatigue syndrome predict population-level fatigue severity and actigraphic measurements.

The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (CFS) is based on a constellation of symptoms which center around fatigue. However, fatigue is commonly reported in the general population by people without CFS. Does the biology underlying fatigue in patients with CFS also drive fatigue experienced by individuals without CFS? We used UK Biobank actigraphy data to characterize differences in physical activity patterns and daily temperature rhythms between participants diagnosed with CFS compared to controls. We then tested if single nucleotide variants (SNVs) previously associated with CFS are also associated with the variation of these actigraphic CFS correlates and/or subjective fatigue symptoms in the general population. Participants diagnosed with CFS (n = 295) had significantly decreased overall movement (Cohen's d = 0.220, 95% CI of -0.335 to -0.106, p-value = 2.42x10-15), lower activity amplitudes (Cohen's d = -0.377, 95% CI of -0.492 to -0.262, p-value = 1.74x10-6), and lower wrist temperature amplitudes (Cohen's d = -0.173, 95% CI of -0.288 -0.059, p-value = 0.002) compared to controls (n = 63,133). Of 30 tested SNVs associated in the literature with CFS, one was associated in the control population with subjective fatigue and one with actigraphic measurements (FDR < 0.05). The genetic overlap of CFS risk with actigraphy and subjective fatigue phenotypes suggests that some biological mechanisms underlying pathologic fatigue in CFS patients also underlie fatigue symptoms at a broader population level. Therefore, understanding the biology of fatigue in general may inform our understanding of CFS pathophysiology.

SpliceTransformer predicts tissue-specific splicing linked to human diseases

We present SpliceTransformer (SpTransformer), a deep-learning framework that predicts tissue-specific RNA splicing alterations linked to human diseases based on genomic sequence. SpTransformer outperforms all previous methods on splicing prediction. Application to approximately 1.3 million genetic variants in the ClinVar database reveals that splicing alterations account for 60% of intronic and synonymous pathogenic mutations, and occur at different frequencies across tissue types. Importantly, tissue-specific splicing alterations match their clinical manifestations independent of gene expression variation. We validate the enrichment in three brain disease datasets involving over 164,000 individuals. Additionally, we identify single nucleotide variations that cause brain-specific splicing alterations, and find disease-associated genes harboring these single nucleotide variations with distinct expression patterns involved in diverse biological processes. Finally, SpTransformer analysis of whole exon sequencing data from blood samples of patients with diabetic nephropathy predicts kidney-specific RNA splicing alterations with 83% accuracy, demonstrating the potential to infer disease-causing tissue-specific splicing events. SpTransformer provides a powerful tool to guide biological and clinical interpretations of human diseases.

Comparative and phylogenetic analysis of the chloroplast genomes of four commonly used medicinal cultivars of Chrysanthemums morifolium

‘Boju’ and ‘Huaiju’ are cultivars of the Chrysanthemum (Chrysanthemum morifolium Ramat.) in the family Asteraceae, valued for their medicinal, tea, and ornamental properties, and valued by individuals. However, the yield and quality of medicinal chrysanthemums are limited by the characteristics of the germplasm resources, including the identification at the varieties and cultivation levels. Currently, research characterizing the chloroplast genomes of medicinal Chrysanthemum flowers is relatively limited. This study conducted chloroplast whole-genome sequencing on two cultivars of Chrysanthemum, ‘Boju’ and ‘Huaiju’, and compared them with the previously published chloroplast genomes of ‘Hangbaiju’ and ‘Gongju’. The study analyzed the chloroplast genome structures of these four medicinal Chrysanthemums, identifying mutation hotspots and clarifying their phylogenetic relationships. The chloroplast genome sizes of four medicinal Chrysanthemum cultivation products ranged from 151,057 to 151,109 bp, with GC content ranging from 37.45% to 37.76%. A total of 134 genes were identified, including 89 protein-coding genes, 37 ribosomal RNA genes, and 8 transfer RNA genes. Comparative genomic analysis revealed 159 large repeat sequences, 276 simple sequence repeats, 1 gene, and 8 intergenic regions identified as highly variable regions. Nucleotide diversity (Pi) values were high (≥ 0.004) for the petN-psbM, trnR-UCU-trnT-GGU, trnT-GGU-psbD, ndhC-trnV-UCA, ycf1, ndhI-ndhG, trnL-UGA-rpl32, rpl32-ndhF, and ndhF-ycf1 fragments, aiding in variety identification. Phylogenetic analysis revealed consistent results between maximum likelihood and Bayesian inference trees, showing that the four medicinal Chrysanthemum cultivars, along with their wild counterparts and related species, evolved as a monophyletic group, forming a sister clade to Artemisia and Ajania. Among the six Chrysanthemum species, the wild Chrysanthemum diverged first (Posterior probability = 1, bootstrap = 1,000), followed by Ajania, while C. indicum and C. morifolium clustered together (Bootstrap = 100), indicating their closest genetic relationship. The chloroplast whole-genome data and characteristic information provided in this study can be used for variety identification, genetic conservation, and phylogenetic analysis within the family Asteraceae.

Polymorphic Loci of Adaptively Significant Genes Selection for Determining Nucleotide Polymorphism of Pinus sylvestris L. Populations in the Urals

Background: Scots Pine is one of the main forest-forming species in boreal forests; it has great economic and ecological significance. This study aimed to develop and test primers for detecting nucleotide polymorphisms in genes that are promising for detecting adaptive genetic variability in populations of Pinus sylvestris in the Urals and adjacent territories. Objectives: The objects of the study were 13 populations of Scots Pine located in the Perm Territory, Chelyabinsk Region, and the Republic of Bashkortostan. Results: Sixteen pairs of primers to loci of potentially adaptively significant genes were developed, from which three pairs of primers were selected to detect the nucleotide diversity of the studied populations. The indicator of total haplotype diversity determined in the three studied loci varied from 0.620 (Pinus-12 locus) to 0.737 (Pinus-11 locus) and, on average, amounted to 0.662. The nucleotide diversity indicators in P. sylvestris in the study region were, on average, low (π = 0.004, θW = 0.013). Their highest values were found at the Pinus-12 locus (π = 0.005; θW = 0.032), and the lowest were found at the Pinus-15 locus (π = 0.003; θW = 0.002). This indicates that Pinus-15 is the most conserved of the three studied loci. In the three studied P. sylvestris loci associated with adaptation to environmental factors, 97 polymorphic positions were identified. The 13 populations of P. sylvestris are characterized by an average level of genetic diversity (Hd = 0.662; π = 0.004; θ = 0.013). Conclusions: The polymorphic loci of adaptively significant genes of P. sylvestris can help identify the adaptive potential of pine forests in conditions of increasing ambient temperatures.