Search Results (112)

Thyroid cancer (TC) is the most common endocrine malignancy, with a rising global incidence. In Ecuador, TC rates are among the highest worldwide. Generally, fine-needle aspiration (FNA) remains the standard diagnostic tool; however, due to its limitations, alternative or complementary approaches are required. In this context, liquid biopsy, particularly circulating tumor DNA (ctDNA), offers a promising, minimally invasive option for tumor genotyping. Objective: This study evaluated the concordance between genetic variants identified in ctDNA and tumor tissue. Thirty-six women with papillary thyroid cancer were included. Tumor tissue and blood samples were collected, and DNA was extracted. Next-Generation Sequencing (NGS) using the TruSight Tumor 15 panel identified genetic variants in both ctDNA and tumor DNA. Variant pathogenicity was assessed following ACMG guidelines. Genetic ancestry was determined using Ancestry Informative Markers (AIMs). A total of 71 cancer-associated variants were detected, with 81.69% concordance between tumor DNA and ctDNA. TP53 was the most frequently mutated gene. While most pathogenic variants were found in tumor tissue, some variants appeared exclusively in ctDNA samples on specific patients, suggesting tumor heterogeneity. Ancestry analysis revealed a predominant Native American component (62.4%). Liquid biopsy demonstrates high concordance with tumor tissue analysis and holds potential as a complementary diagnostic tool for thyroid cancer. However, challenges such as low ctDNA yield and underrepresentation in genetic databases highlight the need for improved protocols and increased inclusion of admixed populations in genomic studies. Full article

To investigate the genetic diversity and structure of farmed Chinese three-keeled pond turtles (Mauremys reevesii), we performed whole-genome resequencing on 238 individuals from eight farms across six Chinese regions. Genetic diversity indices (nucleotide diversity π, inbreeding coefficient F_HOM, polymorphism information content PIC, observed heterozygosity Ho), principal component analysis (PCA), phylogenetic reconstruction, and population structure analysis were integrated. The results revealed that the Guangdong Maoming (MM) and Anhui Wuwei (WW) populations exhibited the highest genetic diversity (MM: PIC = 0.149, Ho = 0.299; WW: PIC = 0.144, Ho = 0.287), while the Guangdong Huizhou (HZ) and Hunan Changhan (CH) populations showed the lowest diversity due to elevated inbreeding coefficients (HZ: F_HOM = 0.043; CH: F_HOM = 0.041). Low genetic differentiation (F_st = 0.00043–0.04758) indicated limited population divergence. However, PCA and phylogenetic analysis demonstrated that MM and Guangxi Pingxiang (PX) populations formed distinct genetic clusters, suggesting that management differences might contribute to their genetic uniqueness. Admixture analysis identified K = 2 (based on the lowest cross-validation error) as the optimal ancestral cluster number, with MM and PX populations displaying admixed genetic backgrounds while others showed homogeneous compositions. Conservation priorities should focus on preserving MM and PX’s unique genetic resources, introducing genetic material to high-inbreeding populations, and establishing interregional breeding networks. This study provides genomic insights for germplasm conservation and sustainable utilisation of M. reevesii. Full article

Background. The coevolution of nuclear and mitochondrial genomes has guaranteed mitochondrial function for millions of years. The introduction of European (EUR) and African (AFR) genomes into the Ameridian continent during the Columbus exchange in Latin America created an opportunity to naturally test different combinations of nuclear and mitochondrial genomes. However, the impact of potential “mitonuclear discordance” (MND, differences in ancestries) has not been evaluated in Latin American admixed individuals (AMR) affected with developmental disorders, even though MND alters mitochondrial function and reduces viability in other organisms. Methods. To characterize MND in healthy and affected AMR individuals, we used AMR genotype data from the 1000 Genomes Project (n = 385), two cohorts of 22q.11 deletion syndrome patients 22qDS-ARG (n = 26) and 22qDS-CHL (n = 58), and a cohort of patients with multiple congenital anomalies and/or neurodevelopmental disorders (DECIPHERD, n = 170). Based on their importance to mitochondrial function, genes were divided into all mitonuclear genes (n = 1035), high-mt (n = 167), low-mt (n = 793), or OXPHOS (n = 169). We calculated local ancestry using FLARE and estimated MND as the fraction of nuclear mitochondrial genes ancestry not matching the mtDNA ancestry and ∆MND as (MNDoffspring—MNDmother)/MNDmother. Results. Generally, MND showed distinctive population and haplogroup distributions (ANOVA p < 0.05), with haplogroup D showing the lowest MND of 0.49 ± 0.17 (mean ± s.d.). MND was significantly lower in 22qDS-ARG patients at 0.43 ± 0.24 and DECIPHERD patients at 0.56 ± 0.12 compared to healthy individuals at 0.60 ± 0.09 (ANOVA p < 0.05). OXPHOS and high-mt showed the same trend, but with greater differences between healthy and affected individuals. Conclusions. MND seems to inform population history and constraint among affected individuals, especially for OXPHOS and high-mt genes. Full article

Wariness is increasing about resident times of microplastics (MPs) in soils; however, limited knowledge is available on ultraviolet (UV) light exposure of MPs to soil fauna. This study investigated the effects of virgin and photoaged polyethylene microplastics (PE MPs) on soil mesofauna (enchytraeids and collembolans) at environmentally relevant concentrations in a microcosm incubation experiment. Ten individuals of each Enchytraeus crypticus and Folsomia candida and twenty Proisotoma minuta were exposed separately to virgin and photoaged PE MPs (40–48 μm) admixed in agricultural soil (0.2–2000 mg/kg) to evaluate reproduction and survival. After 28 d of exposure to photoaged PE MPs, there was a moderate survival reduction but reproduction promotion of E. crypticus. Contrastingly, F. candida exhibited an opposite trend, with survival enhancement and reproduction depression rates when exposed to both PE MP contaminated soils. However, P. minuta was the only species with significant apical endpoint changes after PE MP exposure; at 20 mg/kg photoaged and 2000 mg/kg virgin PE MP exposure, there was a 34% and 31% decrease in survival, respectively, and at 200 mg/kg photoaged PE MP exposure, an increase of 39% for reproduction. PE MPs had contrasting impacts on soil mesofauna species, which highlights the need to account for these variable results when understanding the repercussions of MP pollution on community assemblage and population dynamics in soils. Full article

The Mediterranean trout (currently referred to as Salmo ghigii for Corsican and Italian-native populations) is listed as Endangered in the IUCN Red List, due to fragmented distribution and declining populations across its whole range, and is included in Annex II of the European Habitat Directive. The widespread genome introgression from the invasive Atlantic trout (Salmo trutta), overexploitation, and habitat alterations represent major threats to the persistence of native populations. The LIFE18NAT/IT/000931 STREAMS project aims to enhance conservation status of Mediterranean trout in 6 Italian pilot areas (Maiella, Sibillini Mountains, Casentino Forests and Pollino National Parks, Montemarcello-Magra-Vara Regional Park, and Sardinia with five sites of the Natura 2000 Network), and in 19 transferability areas covering almost the whole Italian species range. To achieve this, the following conservation strategies were implemented: (i) the identification of residual native populations; (ii) eradication of entirely Atlantic-exotic populations and removal of hybrids in admixed populations; (iii) restocking/reintroduction of native populations; (iv) monitoring/improving the Mediterranean trout habitats quality; (v) production of the “Guidelines for the conservation and management of native Mediterranean trout and its habitat”; and (vi) the prevention of illegal stocking. Here, we present the project rationale, major outcomes on demographic and genetic characterization of wild populations, and summary results from conservation actions. Full article

Background: Bighead carp (Hypophthalmichthys nobilis), a vital species in China’s freshwater ecosystems and aquaculture, has experienced significant population declines due to habitat degradation and intensive farming. Methods: In this study, eight polymorphic microsatellite markers were utilized to examine the genotypes and genetic diversity of 320 individuals of bighead carp populations located in the middle Yangtze River. This included four wild populations (ZX, DTH, SS, WH) and six cultured populations (HH, XZ, CH, QC, CD, HG). Results: Wild populations exhibited significantly higher genetic diversity (mean Na = 12.25 ± 0.63, Ho = 0.802 ± 0.063) than cultured groups (mean Na = 8.85 ± 1.21, He = 0.779 ± 0.032). Low differentiation (Fst < 0.05) among wild populations indicated high connectivity with low genetic structure, whereas cultured populations CH and HG showed moderate-to-high differentiation (Fst = 0.156–0.293). Bayesian analysis (K = 7) revealed a distinct clustering of wild populations, while cultured stocks exhibited admixed genetic ancestries. Bottleneck tests confirmed recent genetic bottlenecks in three cultured populations. Conclusions: Wild bighead carp populations retain a critical genetic diversity, serving as reservoirs for conservation, while intensive aquaculture practices threaten genetic integrity through allele loss and inbreeding. Full article

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), poses a significant threat to wheat production in China. Previous epidemic studies have demonstrated the potential of high genetic diversity in the southwest regions of China. Among this epidemic region, the eastern Xizang (Tibet) region holds particular significance, as both wheat and barley crops are susceptible to Pst. However, limited information exists regarding the level of population genetic diversity, reproduction model, and migration patterns of the rust in eastern Xizang. The present study seeks to address this gap by analyzing 146 Pst isolates collected from the Basu, Zuogong, and Mangkang regions, genotyping by the 20K target Gene Array (Genobait). Our results showed relatively low genotypic diversity in the Basu region, while the highest genetic diversity was observed in the Mangkang area. Structural analysis revealed the abundance of admixed groups in Mangkang, which exhibited this population occurred due to sexual recombination between two different ancestor groups. Gene flow was observed between Zuogong and Basu populations, but it almost did not occur between Mangkang and Zuogong/Basu populations. This region is the world’s highest-altitude epidemic area, thus facilitating the evolution of the rust and possessing the potential to transmit newly evolved Pst races to lower wheat-growing regions. Implementing disease management strategies in this area is of potential importance to prevent the transmission of Pst races to other parts of Xizang, even neighboring regions possibly. This study facilitates our understanding of epidemiological and population genetic knowledge and the evolution of Pst in Xizang. Full article

Objectives: To analyze Colombia’s current human population, we employed a population genetics approach enriched by genealogical, demographic, cultural, and historical data to learn about its evolutionary history and to elucidate ethnic belonging and relationship patterns between its various population groups. Materials and Methods: This study relied on ten autosomal microsatellite markers (STRs) from 1364 individuals surveyed throughout the country. Aside from employing descriptive population genetics, substructure, and distance analysis, this investigation evaluated genealogical, demographic, cultural, and historical data gathered from fieldwork surveys. Results: We present a genetic diversity and ethnic belonging map of Colombia that suggests a nine-population classification (under Afro-descendant, Native American, and Admixed ethnicity labels) that reveals traces of evolutionary processes discussed in the light of the recent literature based on modern molecular markers. Colombia’s genetic trace from Africa varies among territories, as shown here by two differentiated Afro ancestral components, Chocó and San Andrés, in addition to the Afro admixture category. Some Native American peoples like the Wayúu, Zenú, Ticuna, Huitoto, and Cocama have a genetic configuration that remains relatively preserved. Nevertheless, other self-determined indigenous peoples who remain in their ancestral territories exhibit genetic introgression that is also reflected by their acculturation levels such as the Pijaos, Kankuamos, and Mokaná. The population classified as European admixture also shows an ancestral component that seems to be more fixed throughout neighboring territories but whose fluctuation depends on its specific demographic histories. Conclusions: This study combines STRs, a targeted sampling strategy, and advanced analytical tools to explore Colombia’s genetic diversity and evolutionary history. Locally, these findings enhance the understanding of genetics in a post-conflict society, crucial for human identification. Globally, they contribute to human population genetics, helping address evolutionary questions using data from diverse human ancestries and geographies. Full article

Background/Objectives: Brazil has a highly admixed population. Polygenic risk scores (PRSs) have mostly been developed from European population studies, and their application to other populations is challenging. To assess the use of PRS for breast cancer (BC) risk in Brazil, we evaluated four PRSs in the Brazilian population. Methods: We analyzed a Brazilian cohort composed of 6206 women with a history of breast cancer and 8878 unphenotyped adults as controls. Genomic variants were imputed from exomes, and scores were calculated for all samples. Results: After individuals with known pathogenic or likely pathogenic variants in BRCA1, BRCA2, PALB2, PTEN, or TP53 genes, and first-degree relatives of the probands were excluded, 5598 cases and 8767 controls remained. Four PRS models were compared, and PRS₃₈₂₀ achieved the best performance, with an odds ratio (OR) of 1.43 per standard deviation increase (p value < 0.001) and an OR of 1.88 (p value < 0.001) for the top decile. PRS₃₈₂₀ also performed well for different ancestry groups: East Asian majority (OR 1.59, p value 0.004), Non-European majority (OR 1.45, p value < 0.001), and European majority (OR 1.43, p value < 0.001). Conclusions: Among the different PRSs, PRS₃₁₃ and PRS₃₈₂₀ could be validated in our Brazilian cohort, with the latter exhibiting the best performance. While further clinical studies are necessary to guide clinical practice, this work represents an important step toward improving BC precision medicine in Brazil. Full article

Background/Objectives: Several genetic factors are related to the risk of Alzheimer’s disease (AD) and the response to cholinesterase inhibitors (ChEIs) (donepezil, galantamine, and rivastigmine) or memantine. However, findings have been controversial, and, to the best of our knowledge, admixed populations have not been previously evaluated. We aimed to determine the impact of genetic and non-genetic factors on the risk of AD and the short-term response to ChEIs and memantine in patients with AD from Mexico. Methods: This study included 117 patients from two specialty hospitals in Mexico City, Mexico. We evaluated cognitive performance via clinical evaluations and neuropsychological tests. Nineteen variants in ABCB1, ACHE, APOE, BCHE, CHAT, CYP2D6, CYP3A5, CHRNA7, NR1I2, and POR were assessed through TaqMan assays or PCR. Results: Minor alleles of the ABCB1 rs1045642, ACHE rs17884589, and CHAT rs2177370 and rs3793790 variants were associated with the risk of AD; meanwhile, CHRNA7 rs6494223 and CYP3A5 rs776746 were identified as low-risk variants in AD. BCHE rs1803274 was associated with worse cognitive functioning. None of the genetic and non-genetic factors studied were associated with the response to pharmacological treatment. Conclusions: We identified potential genetic variants related to the risk of AD; meanwhile, no factor was observed to impact the response to pharmacological therapy in patients with AD from Mexico. Full article

Nonsyndromic cleft lip with or without cleft palate (NSCL ± P) is strongly associated with both environmental and genetic risk factors, but its genetic underpinnings remain partially known. While variants in interferon regulatory factor 6 (IRF6) are linked to NSCL ± P risk in populations from Asia and Europe, studies on the highly admixed Brazilian population are scarce and have produced ambiguous results. This study aimed to investigate the contribution of IRF6 variants to the risk of NSCL ± P. Five tag-single nucleotide polymorphisms (rs599021, rs2073485, rs2235375, rs7552506, and rs642961) were analyzed in a large multicenter cohort composed of 1006 patients with NSCL ± P and 942 healthy controls. Statistical analyses involved multiple logistic regression tests consideration the tri-hybrid genetic origin of the Brazilian population, under a Bonferroni p value correcting for multiple comparisons. The A allele (OR: 1.43, 95% CI: 1.22–1.67, p < 0.0001) and AA genotype (OR: 2.04, 95% CI: 1.46–2.86, p < 0.0001) frequencies of rs642961 were significantly associated with NSCL ± P risk. Stratified analyses indicated that the variant is associated with susceptibility to both nonsyndromic cleft lip only (NSCLO) and nonsyndromic cleft lip and palate (NSCLP). However, the association with NSCLO was primarily observed in patients with high African ancestry, whereas the association with NSCLP was predominantly seen in patients with high European ancestry. No significant associations were found for the other investigated variants. Our results support the notion that the IRF6 rs642961 variant represents a marker of susceptibility to NSCL ± P in the Brazilian population, and that genetic ancestry composition plays a central role in the association with the cleft type. Full article

Crossing Oreochromis niloticus (On) females with O. aureus (Oa) males results in all-male progeny that are essential for effective tilapia aquaculture. However, a reproductive barrier between these species prevents commercial-scale yield. To achieve all-male progeny, the currently used practice is crossing admixed stocks and feeding fry with synthetic androgens. Hybrid tilapias escaping to the wild might impact natural populations. Hybrids competing with wild populations undergo selection for different stressors, e.g., oxygen levels, salinity, and low-temperature tolerance. Forming mitochondrial oxidative phosphorylation (OXPHOS) complexes, mitochondrial (mtDNA) and nuclear DNA (nDNA)-encoded proteins control energy production. Crossbred tilapia have been recorded over 60 years, providing an excellent model for assessing incompatibility between OXPHOS proteins, which are critical for the adaptation of these hybrids. Here, by comparing nonconserved amino acid substitutions, across 116 OXPHOS proteins, between On and Oa, we developed a panel of 13 species-specific probes. Screening 162 SRA experiments, we noted that 39.5% had a hybrid origin with mtDNA-nDNA allele mismatches. Observing that the frequency of interspecific mtDNA-nDNA allele combinations was significantly (p < 10⁻⁴) lower than expected for three factors, UQCRC2, ATP5C1, and COX4B, we concluded that these findings likely indicated negative selection, cytonuclear incompatibility, and a reproductive barrier. Full article

Breast cancer (BC) constitutes a significant global health burden, particularly among women, with disparities observed across populations. Notably, women of African ancestry often experience BC at earlier ages and in more aggressive forms, with a higher prevalence of metastasis. Genetic studies, including those focused on BRCA1 and BRCA2 genes, have revealed population-specific variations in BC susceptibility. Despite efforts to investigate BC genetics in African and African-descendant populations, research remains limited compared to studies conducted in populations of European descent. Socioeconomic factors further compound the challenges faced by marginalized populations, influencing disease outcomes and treatment efficacy. This review explores the BC literature in African and African-descendant populations, highlighting population-specific genetic variants associated with the disease’s subtypes, treatment response, and disease evolution. Limited sample sizes and lack of data on genetic ancestry hinder the development of precise risk stratification and treatment strategies. Efforts to expand research, improve data collection, and enhance genetic analyses in diverse populations are crucial steps toward addressing racial disparities and advancing BC care on a global scale. Full article

Two species of wild sheep inhabit Iran: Asiatic mouflon (Ovis gmelini) and urial (O. vignei). Phylogenetic relationships between populations distributed in this country are complex and still remain unclear. This study aimed to clarify, by genetic assessment, the phylogenetic status of Kerman wild sheep, considered to be a hybrid of the two species. For this purpose, we created a dataset that included specimens of O. gmelini, O. vignei, and Kerman sheep. We applied genome-wide SNP genotyping technology to analyze population structure and genetic diversity of these groups. Using Neighbor-Net and PCA plots, it was demonstrated that Kerman sheep were differentiated from other groups and occupy an intermediate position between O. gmelini and O. vignei. Using Admixture analysis, two ancestral components were identified in this population; however, admixed ancestry was not confirmed by f3 statistics. Genetic diversity in Kerman wild sheep was significantly higher than in any group of O. vignei, but lower than in O. gmelini. Additionally, we examined complete mitochondrial genomes and it was demonstrated that the matrilineal ancestor of Kerman sheep belonged to O. vignei. Our results lead to the conclusion that Kerman wild sheep can be recognized as a separate subspecies of O. vignei. Full article

Latin Americans have a rich genetic make-up that translates into heterogeneous fractions of the autosomal genome in runs of homozygosity (F_ROH) and heterogeneous types and proportions of indigenous American ancestry. While autozygosity has been linked to several human diseases, very little is known about the relationship between inbreeding, genetic ancestry, and cancer risk in Latin Americans. Chile has one of the highest incidences of gallbladder cancer (GBC) in the world, and we investigated the association between inbreeding, GBC, gallstone disease (GSD), and body mass index (BMI) in 4029 genetically admixed Chileans. We calculated individual F_ROH above 1.5 Mb and weighted polygenic risk scores for GSD, and applied multiple logistic regression to assess the association between homozygosity and GBC risk. We found that homozygosity was due to a heterogeneous mixture of genetic drift and consanguinity in the study population. Although we found no association between homozygosity and overall GBC risk, we detected interactions of F_ROH with sex, age, and genetic risk of GSD that affected GBC risk. Specifically, the increase in GBC risk per 1% F_ROH was 19% in men (p-value = 0.002), 30% in those under 60 years of age (p-value = 0.001), and 12% in those with a genetic risk of GSD above the median (p-value = 0.01). The present study highlighted the complex interplay between inbreeding, genetic ancestry, and genetic risk of GSD in the development of GBC. The applied methodology and our findings underscored the importance of considering the population-specific genetic architecture, along with sex- and age-specific effects, when investigating the genetic basis of complex traits in Latin Americans. Full article