Search Results (949)

Endometrial cancer (EC) is the most common gynecologic cancer. Early detection is one of the most important predictors of survival. The cancer is curable if detected early but the five-year survival rate in advanced cases can be as low as 22%. Microsatellite instability (MSI) testing is used to screen populations for Lynch Syndrome (LS), the most common cause of inherited EC, and to classify EC into distinct groups with unique histological, prognostic, and molecular features. Accurate sample identification is crucial for successful MSI testing because instability is assessed by comparing amplification patterns in markers in the normal and tumor samples that must be taken from the same individual. Penta-C and Penta-D pentanucleotide markers are used widely for sample identification in not only MSI testing but also parentage verification, forensic science, and population genetics studies. The objective of this study was to test 324 pairs of tumor and matched normal DNAs from EC patients for instability in these markers using the Promega MSI Analysis System^TM considered the “gold standard” in MSI testing. Both markers were unstable, and therefore not reliable for MSI testing, in 8.2% of the EC patients with MSI. Instability in both mono- and pentanucleotide markers suggest that the tumors with MSI likely suffer from a “generalized” form of instability also affecting other short tandem repeats. Results from many studies using these markers for various purposes may not be accurate if samples with MSI are involved. Full article

Only about 5% of colorectal cancers are hereditary, which is due to the low carrier rate of pathogenic gene mutations. The typical pattern of these cases is intergenerational aggregation within families and early onset. But public awareness of early diagnosis and intervention of HCRC is insufficient, resulting in most patients being diagnosed only after developing cancer, thereby missing the optimal window for treatment. This article reviews the latest developments in precision screening, treatment, evaluation and prevention strategies for HCRC, including innovative uses of artificial intelligence (AI) in molecular diagnostics, imaging technology advances, and potential application prospects. Regarding precision screening, tests of genomics, transcriptomics, microbiome, etc., combined with personalised risk stratification, can, respectively, effectively detect pathogenic mutations and “cancer-promoting” intestinal environments in the preclinical stage. AI combined with endoscopic and imaging tools has improved the accuracy of polyp detection and tumor profiling. Liquid biopsy and molecular marker detection provide new non-invasive monitoring solutions. In precision treatment, beyond traditional approaches like surgery and chemotherapy, immunotherapy with checkpoint inhibitors may be considered for HCRC patients with mismatch repair deficiency (dMMR). For patients harboring somatic mutations such as KRAS or BRAF V600E, targeted therapy can be guided by these specific mutations. Regarding precision assessment, AI incorporates microsatellite instability (MSI) detection and imaging diagnostic techniques, crucial for integrating genetic, environmental, and lifestyle data in follow-up. This helps assess the risk of recurrence and adjust the long-term medication regimens, as well as provide effective nutritional support and psychological counselling. In summary, the rapid development of precision medicine is driving the clinical management of HCRC into the era of tailored care, aiming to optimise patient outcomes. Full article

Background: Early-onset colorectal cancer (EOCRC), defined as diagnosis before the age of 50, is rising rapidly and disproportionately affects high-risk populations, particularly Hispanic/Latino (H/L) individuals, who experience the steepest increases in incidence and mortality. While prevention and screening strategies have curbed late-onset CRC rates, EOCRC remains outside standard screening guidelines and is projected to become the leading cause of cancer-related death in individuals aged 20–49 by 2030. FOLFOX (folinic acid, fluorouracil, and oxaliplatin) is a standard first-line therapy for microsatellite stable (MSS) CRC lacking actionable driver mutations; however, its efficacy and genomic impact in EOCRC, particularly in underrepresented groups, remain poorly understood. The phosphatidylinositol 3-kinase (PI3K) pathway regulates cell growth, survival, and metabolism, and its alterations have been implicated in therapeutic resistance and adverse outcomes. Yet, the prevalence, clinical relevance, and treatment-specific associations of PI3K pathway alterations in EOCRC remain underexplored. Methods: We analyzed somatic mutation and clinical data from 2515 CRC patients (266 H/L and 2249 Non-Hispanic White [NHW]) across publicly available genomic datasets. Patients were stratified by age at diagnosis (EOCRC < 50 vs. LOCRC ≥ 50), ancestry (H/L vs. NHW), and FOLFOX treatment status. PI3K pathway alterations—including mutations in PIK3CA, PTEN, AKT isoforms, and regulatory genes—were identified using curated pathway definitions. Mutation prevalence was compared across groups using Fisher’s exact or chi-squared tests. AI-HOPE-PI3K, a conversational AI platform, was deployed to automate cohort construction, stratify subgroups, and perform post hoc survival analysis. Results: PI3K pathway alterations were observed across all demographic groups. In EO NHW patients treated with FOLFOX, Kaplan–Meier analysis revealed significantly reduced overall survival among those with PI3K pathway alterations (n = 124) compared with their unaltered counterparts (n = 251; p = 0.0008), identifying alterations as a candidate prognostic biomarker in this subgroup. AI-guided subgroup interrogation further highlighted mutation-specific signals: INPP4B and RPTOR emerged as exploratory candidates in EO H/L patients but did not show significant treatment- or ancestry-specific enrichment upon confirmatory testing. Similarly, ancestry-stratified analysis of PIK3R2 mutations revealed comparable rates in EO H/L (1.37%) and EO NHW (1.6%) FOLFOX-treated patients (p = 1.0). Across ancestry and age groups, mutational landscape analysis revealed diverse molecular events—including missense, nonsense, splice-site, frameshift, and in-frame deletions—underscoring the heterogeneity of PI3K pathway dysregulation. Conclusions: This study identifies PI3K pathway alterations as a potential prognostic marker of poor survival in EO NHW patients receiving FOLFOX and uncovers ancestry- and treatment-specific mutational differences in high-risk CRC populations. By integrating clinical, molecular, and treatment variables, the AI-HOPE and AI-HOPE-PI3K platforms enabled rapid, reproducible, and fine-grained analysis of complex datasets. These findings underscore the need for ancestry-informed molecular profiling to optimize therapeutic strategies and highlight AI-guided interrogation as a powerful tool for advancing precision oncology in underrepresented and disproportionately affected CRC populations. Full article

Avocado (Persea americana Mill.) is one of the most widely consumed fruits worldwide. The tree species is traditionally classified into three botanical races: Mexican, Guatemalan, and West Indian (with a potentially distinct Colombian genepool). However, previous studies using molecular markers, such as AFLPs, microsatellites (SSRs), and GBS-derived SNP markers, have only partially resolved this racial divergence, especially in the hyper agrobiodiverse region of northwest South America. Therefore, in order to confirm genetic identity and origin of “criollo” avocado cultivars in the region, as well as to improve their traceability as rootstocks for the Hass variety, we performed low-coverage whole genome resequencing (lcWGS) on 205 ex situ conserved tree samples, comprising 42 commercial varieties and 163 “criollo” trees from various provinces in Colombia. This characterization yielded a total of 64,310,961 SNPs at an average coverage of 4.69×. Population structure analysis using principal component analysis (PCA) and ADMIXTURE retrieved at least five genetic clusters (K = 5), partly confirmed by Bayesian phylogenetic inference. Three clusters matched the recognized Mesoamerican botanical races (Mexican, Guatemalan, and West Indian), and two clusters reinforced the distinctness of two novel Andean and Caribbean Colombian genetic groups. Finally, in order to retrieve high-quality SNP markers for racial screening, a second genomic dataset was filtered, consisting of 68 avocado tree samples exhibiting more than 80% ancestry to a given racial cluster, and 9826 SNPs with a minimum allele frequency (maf) of 5%, a minimum sequencing depth (SD) of 10× per position, and missing data per variant not exceeding 20% (i.e., variants with genotypes present in at least 80% of the samples). This racially segregating high-quality subset was analyzed against the racial substructure using linear mixed models (LMMs), enabling the identification of 254 SNP markers associated with the five avocado genetic races. The previous candidate SNPs may be leveraged by nurseries and producers through a high-throughput SNP screening system for the racial traceability of seedling donor trees, saplings, and rootstocks. These genomic resources will support the selection of regionally adapted elite rootstocks and represent a landmark in Colombian horticulture as the first large-scale lcWGS-based characterization of a local avocado germplasm collection. Full article

Corylus avellana L. is a rare and endangered species in Kazakhstan, included in the national Red Book. The results of morphological and genetic characterization of the sole known natural population of C. avellana in the Western Kazakhstan region are presented in this study. Sixty wild accessions were evaluated based on tree and leaf morphological traits using standard descriptors in accordance with Bioversity International guidelines. Genetic diversity was assessed using ten nuclear simple sequence repeat (SSR) markers. A total of 120 alleles were detected across the nuclear loci, with the number of alleles per locus ranging from 9 to 16 and an average of 12. The mean effective number of alleles (Ne) per locus was 3.862. A high level of intraspecific polymorphism was observed, with an average observed heterozygosity (Ho) of 0.70. The population showed considerable genetic diversity, as highlighted by a mean Shannon’s diversity index of 1.526. STRUCTURE, PCoA, and phylogenetic analyses confirmed strong differentiation between the wild Kazakh population and the cultivated hazelnut germplasm. Due to the lack of viable seeds, in vitro conservation was initiated using vegetative shoots. A two-step disinfection protocol, involving Plant Preservative Mixture and mercuric chloride, significantly improved explant survival, enabling successful establishment of an aseptic in vitro collection. These findings highlight the urgent need for targeted conservation strategies and show the potential of biotechnological approaches for safeguarding Kazakhstan’s only natural C. avellana population. Full article

We conducted a comparative analysis of the identified microsatellite sequences across the genomes of nine sillaginids. We examined the microsatellites with motifs ranging from 1 to 6 bp in length and analyzed their distribution and frequency across different genomic regions. Microsatellite occurrence differed significantly with the degree of coverage ranging from 1.47 to 3.21%. The number and proportion of each repeat type were consistent across the nine species, with di-nucleotide repeats being the most abundant, followed by mono-nucleotide repeats, and gradually decreasing as the number of repeat units increased. The mono-nucleotide repeat motifs were dominated by A/T, while di-nucleotide repeat motifs were mainly AC/GT, and tri-nucleotide repeat motifs were primarily AGG/CCT. Regarding the number of repeats, microsatellites in Sillaginidae were generally concentrated between 5 and 18 repeat units, with peaks observed at 6 and 10 repetitions. The abundance of microsatellite loci consistently decreased as the number of repetitions increased beyond 10. These findings provide valuable insights into genome evolution and microsatellite DNA dynamics, supporting future investigations into their structural and functional characteristics, compositional patterns, and applications in molecular marker development for these species. Full article

The Blackspot Seabream, Pagellus bogaraveo, is a commercially valuable species widely distributed in the northeastern Atlantic and Mediterranean. Its biology makes it vulnerable to overfishing, but its population structure and ontogenetic migration strategy remain unclear. Building on previous work based on microsatellite markers, we expanded the investigation by analysing the mitochondrial Control Region (CR) to complement nuclear data. We analysed 199 specimens from 13 sites and combined the new CR sequences with 129 published records to achieve the broadest coverage in terms of biogeographic and genetic data. We calculated genetic diversity and performed AMOVA, pairwise ΦST comparisons, and multivariate analyses. Eighty-eight haplotypes were identified, showing high haplotype diversity (Hd = 0.767–0.945) and moderate nucleotide diversity (π = 0.0026–0.0054). Most genetic variation occurred within populations, and overall analyses indicated genetic homogeneity. However, pairwise analysis and AMOVA confirmed significant differentiation of the Azores population. These results confirm extensive genetic connectivity throughout the Atlantic–Mediterranean range of P. bogaraveo, likely due to a combination of large larval dispersal and a common spawning migration strategy, but identify the Azores as a genetically distinct unit. This highlights the need to consider both large-scale connectivity and local divergence in fisheries management. Full article

Angulyagra polyzonata is a significant freshwater snail species in southern China. However, its wild resources have sharply declined due to overfishing. To assess the current status of germplasm resources in the Guangxi region, during this study, we first successfully developed nine pairs of primers that enable the amplification of highly polymorphic microsatellite markers (SSRs) with trinucleotide and tetranucleotide repeat sequences (PIC values ranging from 0.662 to 0.861) using transcriptomic data. Then, these designed primers were tested and applied for the genetic investigation of selected wild populations of the species. Finally, a genetic diversity analysis was conducted based on 12 wild populations (360 individuals) in Guangxi. After 798,244 SSR loci were screened out via high-throughput sequencing, the results showed that dinucleotide repeats accounted for the highest proportion (47.64%), mainly consisting of (AC/GT)n repeat units. Among the SSR loci in A. polyzonata, microsatellite loci with 5 to 20+ repeats are the most abundant. All nine selected and tested SSR loci significantly deviated from Hardy–Weinberg equilibrium (p < 0.001) and had heterozygote deficiency (average inbreeding coefficient of F = 0.390), indicating widespread inbreeding. The fixation index among populations was high (average Fst = 0.175), with 73% of the genetic variation occurring within populations and 27% between populations. Gene flow (Nm) was generally restricted (most population pairs had Nm < 1), with the (Tiandeng) TD and (Long’an) LA populations showing the smallest differentiation (Fst = 0.017), and the (Qinnan) QN and (Yinhai) YH populations showing the greatest differentiation (Fst = 0.409). UPGMA clustering and structure analysis (K = 2) divided the 12 populations into two subgroups. Overall, our research suggests that the genetic diversity of the wild population of A. polyzonata in the Guangxi region has declined. Thus, prioritizing the protection of highly genetically diverse populations, such as the LA population, is urgently needed. This study provides a scientific basis for the protection and sustainable utilization of A. polyzonata resources in Guangxi. Full article

Studies of the genetic diversity of ‘Candidatus Liberibacter asiaticus’ strains based on housekeeping genes have been unsuccessful. The increasing availability of complete genome sequences of several strains from different countries has allowed the identification of regions having greater variability, which have been successfully implemented for the bacterium characterization, including microsatellites, genes of prophage origin, and miniature transposable elements with inverted-repeats (MITEs). In the present work, the genetic structure of 147 ‘Ca. L. asiaticus’ strains from nine provinces of Cuba were investigated using two polymorphic regions, consisting of typing for prophages and MITEs. The results showed an important level of coexistence of type 1 and 2 prophages in the Cuban strains, while the type 3 prophage was not detected. Likewise, a high rate of co-occurrence of both types of MITEs (MCLas-A and -B) was also observed. However, the MITE MCLas-A was detected only in its empty form. The double-locus analysis allowed the identification of eight genotypes. Out of these, seven genotypes were present in the Western region, which constitutes the region with the highest genetic variability. This is the first report of a genetic characterization of Cuban strains of ‘Ca. L. asiaticus’ with polymorphic markers in orchards growing in commercial citrus regions. Full article

Fusobacterium nucleatum (Fn) has been increasingly recognized as a crucial mediator of colorectal cancer (CRC) biology, particularly in microsatellite-stable (MSS) tumors, where immune checkpoint inhibitors (ICIs) have shown limited efficacy. Rather than representing a passive microbial passenger, Fn actively shapes tumor behavior by adhering to epithelial cells, activating oncogenic signaling, and promoting epithelial–mesenchymal transition (EMT). At the same time, it remodels the tumor microenvironment, driving immune suppression through inhibitory receptor engagement, accumulation of myeloid-derived cells, and metabolic reprogramming of tumor-associated macrophages. These mechanisms converge to impair cytotoxic immunity and contribute to both intrinsic and acquired resistance to ICIs. Beyond immune escape, Fn interferes with conventional chemotherapy by sustaining autophagy and blocking ferroptosis, thereby linking microbial colonization to multidrug resistance. Most of these mechanisms derive from preclinical in vitro and in vivo models, where causal relationships can be inferred. In contrast, human data are mainly observational and provide correlative evidence without proving causality. No interventional clinical studies directly targeting Fn have yet been conducted. Its enrichment across the adenoma–carcinoma sequence and consistent detection in both tumor and fecal samples highlight its potential as a biomarker for early detection and patient stratification. Importantly, multidimensional stool assays that integrate microbial, genetic, and epigenetic markers are emerging as promising non-invasive tools for CRC screening. Therapeutic strategies targeting Fn are also under exploration, ranging from antibiotics and bacteriophages to multifunctional nanodrugs, dietary modulation, and natural microbiota-derived products. These approaches may not only reduce microbial burden but also restore immune competence and enhance the efficacy of immunotherapy in MSS CRC. Altogether, current evidence positions Fn at the intersection of microbial dysbiosis, tumor progression, and therapy resistance. A deeper understanding of its pathogenic role may support the integration of microbial profiling into precision oncology frameworks, paving the way for innovative diagnostic and therapeutic strategies in CRC. Full article

Cannabis sativa L. (2n = 2x = 20) is a widely recognized species within the Cannabaceae family. Despite its utilization for medicinal, recreational, and industrial purposes, alongside its extensive historical background, the number of genetic and biotechnological studies of this plant species has decreased due to legal ramifications and prohibition campaigns associated with its use and cultivation. For many years, the development of novel varieties has been pursued solely by cultivators, as domestic growers have transitioned their work from cultivation to breeding Cannabis lineages. Recently, the application of genomics has facilitated a surge in methodologies aimed at marker-assisted selection, germplasm management, genetic differentiation, authentication of cultivated varieties or cultivars, and forensic applications such as safeguarding intellectual property rights. Nevertheless, the utilization of molecular markers for the advancement of commercial varieties through marker-assisted breeding (MAB) frameworks remains rare. This investigation was designed to evaluate a previously established informative microsatellite (SSR) array for the genotyping of drug-type Cannabis sativa cultivars derived from seeds of European origin. A total of 171 samples from 20 varieties were collected from European distributors and analyzed for genetic uniformity and population structure. The results were then compared with previously analyzed hemp samples and drug-type samples of Canadian origin, revealing the identification capabilities of our SSR genotyping method. Full article

Background: Extra digits on the hands and/or feet are a frequent condition known as polydactyly. Twelve nonsyndromic polydactyly genes have been identified, including KIAA0825. Methods: Four consanguineous Pakistani families that segregate nonsyndromic postaxial polydactyly (PAP) with an autosomal recessive mode of inheritance were clinically and genetically evaluated. Exome sequencing or genotyping of polymorphic microsatellite markers followed by Sanger sequencing were used to identify the variants underlying the PAP etiology. Results: Three novel KIAA0825 variants were identified that segregate with PAP: a nonsense variant c.2319G>A; p.(Trp773*) in two families; a missense variant c.970G>T; p.(Val324Phe) in one family; and a four amino acids in-frame deletion c.2743_2754del; p.(Gln915_Val918del) in one family. The nonsense variant segregated in families with PAP type B (PAPB), while the missense and the in-frame deletion variants segregated with PAP type A and B. Conclusions: The findings of this study expanded the clinical and genetic spectrum of PAP due to KIAA0825 variants including the first KIAA0825 variant specific to PAPB. Full article

Determining evolutionary significant units (ESUs) is essential for the purpose of biological conservation. Recent definitions of ESUs stress the importance of using ecological data with molecular analysis. The present work aimed to study the genetic structure and ecological niche of the spur-thighed tortoise (Testudo graeca) in its contact zone, with a special focus on hybridization between T. g. buxtoni and T. g. zarudnyi in Central Iran using a combination of genetic data (microsatellite markers) and ecological niche modeling (ENM). Our results indicated that despite the distinct mitochondrial clades, nuclear markers reveal gene flow between the two subspecies, especially in the contact zone, with the majority of hybrids belonging to T. g. zarudnyi. The genetic structure of T. graeca reflects a complex interplay of ancient vicariance and recent gene flow. While mitochondrial markers suggest long-term separation, nuclear markers reveal more recent hybridization events. The results obtained from ENMs demonstrated the niche differentiations. Climatic variables, such as annual rainfall and temperature seasonality, primarily drive the distribution of both subspecies. The western clade is associated with higher precipitation and lower temperature variability. These findings suggest that both subspecies hold valuable evolutionary and conservation issues. Based on these mentioned results, we strongly recommend assigning the two subspecies as ESUs to enhance the accuracy of conservation measurements. We believe that understanding the ecological factors influencing species distribution, along with molecular analysis under the recent concept of ESUs, can provide valuable insights into the conservation and management of the T. graeca complex in its wide geographic range. Full article

This study aimed to generate information for parentage testing in horse breeds using microsatellites (STRs) and single-nucleotide polymorphisms (SNPs). Genotype data were obtained from 189 horse hair root samples, including 38 Thoroughbreds (TBs), 17 Jeju horses (JHs), 20 Quarter horses (QHs), 21 American Miniatures (AMs), and 93 Mongolian horses (MHs), using 15 STR markers and 71 SNP markers. Comparative analysis revealed that the mean expected heterozygosity ranged from 0.468 (AM) to 0.491 (JH) for SNPs and from 0.695 (TB) to 0.791 (MH) for STRs. The mean observed heterozygosity ranged from 0.415 (AM) to 0.487 (MH) for SNPs and from 0.706 (JH) to 0.776 (MH) for STRs. The mean polymorphic information content ranged from 0.349 (AM) to 0.364 (MH) for SNPs and from 0.635 (TB) to 0.761 (MH) for STRs. The inbreeding coefficient ranged from −0.009 (MH) to 0.113 (AM) for SNPs and from −0.058 (TB) to 0.043 (AM) for STRs. The cumulative exclusion probability (PE) for the 71-SNP panel exceeded 0.9999, indicating that SNP markers may be sufficient for parentage testing. In comparison, the STR markers yielded a combined PE of 0.9988 when one parent was known and 0.9999 when both parents were known. These findings highlight the potential of SNPs as alternatives to STRs for routine paternity verification in horses. Full article

The study of horse genetic diversity is imperative for informing conservation strategies, safeguarding ancestral lineages, and enhancing breed adaptability to environmental and disease pressures. This study employed 13 microsatellite markers with fluorescent-labeled capillary electrophoresis to analyze the genetic diversity of the Kyrgyz horse (n = 30) and Barkol horse (n = 30) for the first time, comparing them with three other indigenous horse breeds (n = 30 per breed) from Xinjiang, China. A total of 208 alleles were detected. The Polymorphic Information Content (PIC) results from GenAlEx 6.5115 show that all loci, except for the HTG06 locus in the Yanqi horse races, were highly polymorphic (PIC > 0.5), indicating a high level of genetic diversity across the five races. Among the five races, the Kyrgyz horse exhibited the lowest mean values for the effective number of alleles (Ne), observed heterozygosity (Ho), and expected heterozygosity (He), which were 6.025, 0.737, and 0.810, respectively. In contrast, the Barkol horse showed the highest mean number of alleles (Na), Ne, and He values, at 11.308, 6.330, and 0.816, respectively. Principal Coordinate Analysis (PCoA), performed using GenAlEx 6.5115, revealed the smallest genetic distance between the Kyrgyz and Yanqi horse breeds. Combined with phylogenetic tree and clustering analysis results, this supports the hypothesis that the two breeds share a common origin. This study offers valuable scientific insights for conserving and utilizing the genetic resources of indigenous Xinjiang horse breeds, specifically the Kyrgyz and Barkol horses. Full article