Search Results (142)

Expanded carrier screening (ECS) has emerged as a cornerstone of reproductive genetics, enabling the identification of couples at risk of transmitting autosomal recessive and X-linked disorders. Advances in next-generation sequencing and the increasing adoption of exome- and genome-based strategies have greatly expanded its clinical scope. However, despite existing national and international recommendations, substantial heterogeneity remains in gene panel composition, inclusion criteria, and interpretation frameworks. A key novelty of the current genomic era is the availability of large, publicly accessible human genome datasets encompassing broader ancestral diversity. These resources are transforming our understanding of variant frequencies and disease penetrance across populations, supporting the development of evidence-based and ancestry-informed gene panels. In parallel, recent studies investigating the genetic contribution of pathogenic variants to euploid pregnancy losses are opening new perspectives for ECS. Incorporating genes associated with lethal conditions in utero may enhance the predictive power of screening and deepen our understanding of reproductive outcomes, while also demanding careful consideration of clinical validity and counseling implications. This mini-review synthesizes current evidence on ECS, examines ongoing interpretive and implementation challenges, and discusses how population-scale genomic resources and emerging data on reproductive lethality are shaping the next generation of evidence-based carrier screening. Full article

Background/Objectives: Establishing the identity of unknown individuals has always been one of the primary objectives of anthropologists and forensic pathologists in judicial contexts. Particularly when human remains are found in advanced stages of decomposition, carbonization, or fragmentation conditions that may compromise the efficacy of techniques such as DNA analysis or dental comparison innovative methodologies, including craniofacial superimposition, are employed, often supplemented by further examinations. This study presents the discovery of an individual in an advanced state of decomposition, transitioning from the colliquative to the semi-skeletal phase, demonstrating how degenerative processes can alter soft tissues to the extent of hindering genetic investigations. Methods: The multidisciplinary investigation conducted to resolve the case is described in two phases: the first, of an anthropological and medico-legal nature, aimed at reconstructing the biological profile (sex, age, stature, ancestry); the second, anthropological in focus, directed toward identification through craniofacial superimposition, applying two established methods from the literature the linear method and the computer-assisted comparison approach. Results: The results obtained from both investigative phases proved decisive, providing a significant and anticipated resolution for the authorities involved. Conclusions: This judicial case ultimately reaffirms the critical importance of multidisciplinary collaboration in forensic investigations. Full article

Genealogy is a powerful analytical framework for understanding the cultural evolution of tribes, communities, and societies. This article demonstrates that the recurrent reliance on genealogical structures is a common feature of human societies, serving as a fundamental mechanism for cultural evolution through time, space, and culture. Based on comparative analysis of indigenous tribal societies (e.g., Aboriginal Australian kinship, Polynesian chiefly genealogies), agrarian civilizations (e.g., European feudal lineages, Chinese patriliny), and modern nation-states (e.g., nationalist mythmaking, DNA-based ancestry movements), this study reveals consistent patterns in genealogical functions. Drawing on an interdisciplinary perspective from anthropology, sociology, history, and evolutionary biology, it is argued that genealogical systems are not passive records of descent but dynamic forces of cultural continuity and adaptation. The evidence shows that, despite vast sociocultural differences, genealogy widely operates as a dual-purpose instrument. It preserves cultural memory and legitimizes political authority while simultaneously facilitating social adaptation and innovation in response to new challenges. The paper also critiques contemporary trends like commercial genetic genealogy, highlighting its potential for reconnecting diasporic communities alongside its risks of biological essentialism. Ultimately, the work establishes that the persistent and patterned reliance on genealogy from oral traditions to genetic data offers a critical lens for understanding the deep structures of cultural continuity and transformation in human societies. It further underscores the importance of genealogy in cultural evolution, historical persistence, societal transformation, and the construction of belonging in an increasingly globalized world. Full article

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those of European or Asian descent. Identifying microRNA (miRNA) signatures that contribute to these disparities may enhance prognostic accuracy and inform personalized therapeutic strategies. Methods: In this study, we identified prognostic markers of overall survival in serous ovarian cancer (SOC) using data from The Cancer Genome Atlas (TCGA) and the Human Protein Atlas. Integrative bioinformatic analyses revealed three key prognostic genes—TIMP3 (Tissue Inhibitor of Metalloproteinases-3), BRAF (v-raf murine sarcoma viral oncogene homolog B), and ITGB1 (Integrin Beta-1)—as critical molecular determinants associated with survival in patients with SOC. Candidate miRNAs regulating these genes were predicted using TargetScanHuman v8.0, identifying a core regulatory set comprising miR-192, miR-30d, miR-16-5p, miR-143-3p, and miR-20a-5p. To validate their clinical relevance, formalin-fixed, paraffin-embedded (FFPE) and fresh SOC tumor samples were obtained from African American and Caucasian patients who underwent surgery at Loma Linda University (LLU) between 2010 and 2023. Results and Discussion: Among all these, ITGB1 (p = 0.00033), TIMP3 (p = 0.0035), and BRAF (p = 0.026) emerged as statistically significant predictors. Following total RNA extraction, cDNA synthesis, and quantitative reverse transcription PCR (qRT-PCR), the expression levels of these miRNAs and their target genes were quantified. In the LLU cohort, ITGB1 and TIMP3 were significantly upregulated in African American patients compared to Caucasian patients (p < 0.01 and p < 0.02, respectively). Among the miRNAs, miR-192-5p was particularly noteworthy, showing marginally differential expression in LLU samples (p = 0.0712) but strong statistical significance in the TCGA cohort (p = 0.00013), where elevated expression correlated with poorer overall survival (p = 0.021). Pathway enrichment and gene ontology analyses (miRTargetLink2.0, Enrichr) revealed interconnected regulatory networks linking miR-192, miR-16-5p, miR-143-3p, and miR-20a-5p to ITGB1; miR-143-3p/miR-145-5p to BRAF; and miR-16-5p and miR-30c/d to TIMP3. Conclusions: Collectively, these findings identify distinct miRNA–mRNA regulatory signatures—particularly the miR-192-5p–ITGB1/TIMP3 axis—as potential clinically relevant biomarkers that may contribute to racial disparities and disease progression in ovarian cancer. Full article

Background/Objectives: Previous studies suggest that nutrient deficiencies can alter immune responses in animals. However, the impact of micronutrients on autoimmune diseases like type 1 diabetes (T1D) in humans remains unclear since the described associations are based on observational data and they cannot establish causality. This study aims to examine the causal relationship between various micronutrients and T1D using Mendelian randomization (MR). Methods: We performed a two-sample MR analysis using genetic variants from genome-wide association studies (GWASs) of 17 micronutrients as instrumental variables (IVs). We analyzed T1D GWAS datasets of European (18,942 cases/520,580controls), multi-ancestry (25,717 cases/583,311 controls), Latin American/Hispanic (2295 cases/55,134 controls), African American/Afro-Caribbean (6451 cases/109,410 controls), and East Asian (1219 cases/132,032 controls) ancestries. We applied the inverse variance weighted (IVW) method in our main analysis, and additional MR estimators (MR-Egger, weighted median, weighted mode, MR-PRESSO) to address pleiotropy, and the Steiger test to test directionality in sensitivity analyses. Results: Following Bonferroni correction (p < 0.05/17), we found positive association between potassium levels and T1D risk (OR = 1.098, 95% CI [1.075, 1.122] p = 5.5 × 10⁻¹⁸) in the multi-ancestry analysis. Zinc, vitamin B12, retinol, and alpha tocopherol showed nominal associations. Vitamin C, D, K1, B6, beta- and gamma-tocopherol, magnesium, iron, copper, selenium, carotene, and folate showed no significant effects on T1D risk. For the multi-ancestry analysis, we had sufficient power to detect ORs for T1D larger than 1.065. Conclusions: Higher serum potassium levels were associated with increased T1D risk in our MR study, though supporting observational evidence is currently limited. Other micronutrients are unlikely to have large effects on T1D. Full article

This study examines the construction of individual and collective identity in pre-Neolithic Egypt and the Levant through the post mortem manipulation of human remains. Focusing on funerary rituals and skull reuse, interpreted using recent anthropological theory frameworks, we propose a totemic framework of ontological identity, in which clans associated with specific animals structured their ritual and spatial practices. Based on archaeological, taphonomic, and ethnohistorical evidence, it is possible to identify how these practices reflect clan-based social units, seasonal mobility, and a reciprocal relationship with the environment, integrating corporeal and mental continuity. Plastered skulls in the Levant acted as intergenerational anchors of communal memory, while early Egyptian dismemberment practices predate the standardization of mummification and reveal the function of some structures of pre-Neolithic sanctuaries. By interpreting these mortuary rituals, we argue that selective body treatment served as a deliberate mechanism to reinforce totemic identity, transmit ancestry, and mediate ontological transitions in response to sedentarization and environmental change. Full article

This article reflects on the fading of personal and familial histories in the context of migration, trauma, and cultural transformation. While modern tools such as ancestry kits and digitized records promise clarity about our roots, they often fail to capture the emotional and narrative legacies that define us. Drawing on scholars such as Jan Mason, Gayatri Chakravorty Spivak, and Saidiya Hartman, this piece explores the silence that surrounds intergenerational memory. Whether caused by disruption, grief, or survival, silence is shown to be both an absence and a form of protection. The editorial calls for greater intentionality in preserving stories through conversation, documentation, and creative expression as a way to resist erasure and affirm identity in the face of historical neglect. In a world where wars, migration, and climate disasters are uprooting millions, we risk losing not just homes but the stories, languages, and rituals that carry who we are. This piece is a call to hold on to those fragile histories beyond the facts and dates, so that what is most human in our past is not silenced by the speed and forgetting of the present. Full article

The ancestry of domestic species from their closest wild relatives is one of the most debated and intriguing topics in evolutionary genetics. This review synthesizes current scientific understanding of the phylogenetic relationships between wild mouflon populations and domestic sheep (Ovis aries). It delves into the complex ancestry, tracing the primary role of the Asiatic mouflon (Ovis gmelini) as the progenitor, while also addressing the debated contributions of other wild Ovis species. The report explores the insights gained from diverse genetic markers, including mitochondrial DNA haplogroups and comprehensive whole-genome sequencing, highlighting their strengths, limitations, and the resolution of phylogenetic discrepancies. The multi-faceted taming process is examined, discussing proposed evolutionary mechanisms such as the domestication syndrome and thyroid hormone hypotheses, alongside human-mediated selection for key phenotypic traits like horn morphology, coat type, and tail characteristics. Furthermore, the pervasive role of hybridization and introgression between wild and domestic populations is analyzed, detailing its impact on genetic distinctiveness, adaptive potential, and the critical implications for conservation strategies. Finally, the review addresses ongoing scientific debates, particularly concerning the taxonomic classification of European mouflon, and identifies crucial avenues for future research to further unravel the intricate evolutionary tapestry of Ovis species. To ensure taxonomic consistency and promote conservation, nomenclature should be updated across all public repositories. Following the widely accepted classification that recognizes its lineage from the Asian mouflon, the Corsican and Sardinian mouflon should be designated as Ovis gmelini musimon. Full article

Copaifera langsdorffii is a neotropical tree widely distributed in the Brazilian Atlantic Forest and Brazilian Savanna. Population genetic analyses can identify the scale at which tree species are impacted by human activities and provide useful demographic information for management and conservation. Using a Restriction site Associated DNA Sequencing approach, we assessed the genomic variability of six C. langsdorffii population relicts in a transition zone between the Seasonal Atlantic Forest and Savanna biomes in Southeastern Brazil. We identified 2797 high-confidence SNP markers from six remnant populations, with 10 to 29 individuals perpopulation, in a transition zone between the Seasonal Atlantic Forest and Savanna biomes in Southeastern Brazil. Observed heterozygosity values (0.197) were lower than expected heterozygosity (0.264) in all populations, indicating an excess of homozygotes. Differentiation among populations (F_ST) was low (0.023), but significant (0.007–0.044, c.i. 95%). A clear correlation was observed between geographic versus genetic distances, suggesting a pattern of isolation by distance. Bayesian inferences of population structure detected partial structuring due to the transition between the Atlantic Forest and the Brazilian Savanna, also suggested by spatial interpolation of ancestry coefficients. Through the analysis of F_ST outliers, 28 candidates for selection have been identified and may be associated with adaptation to these different phytophysiognomies. We conclude that the genetic variation found in these populations can be exploited in programs for the genetic conservation of the species. Full article

Mitochondria are essential organelles for cellular energy production, playing a central role in driving metabolic processes and supporting critical intracellular functions. Neurometabolic disorders encompass a wide variety of conditions characterized by mitochondrial dysfunction. Owing to their bacterial ancestry, mitochondria possess an independent genome consisting of a circular DNA molecule (mtDNA), which has been reported to be subject to methylation. However, the technical challenges in the detection of mtDNA methylation have led to debates on its existence. One of the concerns is that the compactness of mtDNA can lead to suboptimal bisulfite conversion, thereby causing mtDNA methylation overestimation. To address this, liquid chromatography tandem mass spectrometry (LC-MS/MS) offers a bisulfite-independent readout; however, this method requires mtDNA samples devoid of nuclear DNA (nDNA) contamination. To diminish nDNA contamination, we isolated mtDNA from the TRIzol RNA phase. Importantly, pyrosequencing showed no significant difference in the methylation levels of mtDNA isolated from the TRIzol RNA phase compared to those from the TRIzol DNA phase, or isolated via total genomic DNA (gDNA). Across different human cell lines, LC-MS/MS detected significantly lower global methylation levels for DNA isolated from the TRIzol RNA phase than those from the TRIzol DNA or gDNA isolation. Moreover, using mtDNA isolated from the TRIzol RNA phase, LC-MS/MS validated the enhanced mtDNA methylation in HepG2 transgenic cell lines expressing mitochondrial-targeted DNA methyltransferases (means of 2.89% and 2.03% for MCviPI and MSssI transgenic cell lines, respectively), compared to two negative control cell lines (1.36 and 1.39%). When applying it to clinically relevant material, LC-MS/MS demonstrated a significantly lower global methylation level for platelet DNA isolated from the TRIzol RNA phase (mean of 1.98%) compared to gDNA isolations (mean of 4.32%). Similar findings were confirmed in mouse brain tissue, in which a significantly lower methylation level was detected in DNA isolated from the TRIzol RNA phase (1.79%) compared to that from gDNA isolation (5.12%). In conclusion, isolating mtDNA from the TRIzol RNA phase holds significant potential in future studies, particularly for the quantification of mtDNA global methylation by LC-MS/MS, a technique that is independent of bisulfite conversion and bioinformatic analysis. Full article

Some of Spain’s greatest humanists—Juan Luis Vives, Antonio de Nebrija, Juan de Ávila, Luis de León, and Benito Arias Montano—were from a converso background. Recent scholarship suggests that two of the three most influential religious movements in sixteenth-century Spain—Juan de Ávila’s evangelical movement and Teresa of Ávila’s Barefoot Carmelites—were founded by conversos and presented converso membership, whose winds of religious innovation to tame Christian Orthodoxy and Counter-Reformation Spanish society, through the influence of Italian Humanism and reform, prioritized spiritual practice, social toleration, and religious concord. Indeed, Santa Teresa de Ávila, a major innovator within the Spanish Church, was herself from a converso family with Jewish ancestry. She became a key female theologist who transcended as an identity marker of the Spanish Baroque, conceived as quintessential of the Spanish Golden Age. Coopted in different periods, she “reappeared” in the 1930s as Patron of the Sección Femenina de la Falange y de las JONS, the women’s branch of the new radical right, turning into a role model of femininity for highly conservative religious women. Consecrated as “Santa de la Raza”, she became the undisputable womanized icon of the so-called “Spanish Crusade”, the slogan which General F. Franco implemented, with the approval of the Spanish Catholic Church, to re-cast in a pseudo-theological narrative the rebellion against the Spanish Second Republic in July 1936. This article examines different appropriations of the figure of Teresa de Ávila as a pillar of “Hispanidad”, in the last centuries within the changing sociopolitical contexts and theological debates in which this instrumentalization appeared. By highlighting the plasticity of this converso figure, the article suggests possible lines of research regarding the Jewish origins of some national icons in Spain. 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

A variable number tandem repeat polymorphism has been described in the CYP2C9 promoter (pVNTR) with three types of fragments: short (pVNTR-S), medium (pVNTR-M), and long (pVNTR-L). The pVNTR-S allele appears in strong linkage disequilibrium (LD) with the non-functional CYP2C9*3 allele in populations of European ancestry, but independently of this, it also appears to reduce the level of CYP2C9 expression in human liver by up to 34%. Objectives: This study, in a Dominican population with varying amounts of Western European, African, and Native American ancestry, aims primarily to determine the frequency of CYP2C9 pVNTR, and the degree of LD of pVNTR-S with CYP2C9*3. Secondarily, it explores if the frequency of the pVNTR-S allele is over- or under-represented in those with a greater component of African ancestry. Methods: A total of 193 healthy volunteers from the Dominican Republic participated in the study. The promoter region of CYP2C9 was amplified and analyzed by capillary electrophoresis. Analyses of CYP2C9 genotypes (*2, *3, *5, *6, and *8) and genetic ancestry, estimated in 176 Dominican individuals by genotyping 90 ancestry informative markers, were previously performed in this population. Results: The frequencies of CYP2C9 pVNTR-L, M, and S variants are 0.065, 0.896, and 0.039, respectively. LD between pVNTR-S and CYP2C9*3 was found (D’ = 0.756, r² = 0.702) to be weaker than in European populations. Conclusions: Populations with a greater African ancestry component appear to present a lower-than-expected frequency of pVNTR-S, as well as a lower tendency for this and CYP2C9*3 alleles to be inherited together, as is common in Europeans. The present exploratory results warrant further research in vivo about the effects of pVNTR-S in predicting CYP2C9 activity. Its inclusion in CYP2C9 testing panels for personalized drug therapy could be relevant in populations such as the Dominican, where the LD between pVNTR-S and CYP2C9*3 is low. Full article

Background/Objectives: Identification of human remains is of utmost importance for criminal investigations and providing closure to the families. The reconstruction of a biological profile of the individual will narrow down the list of candidates for identification. From another perspective, facial approximations performed by a forensic artist can provide investigative leads, with the identity being confirmed by primary or secondary methods of identification. In recent years, DNA analysis has evolved, trying to create a portrait of the perpetrator/victim based on External Visible Characteristics (EVCs), the color of the eyes, hair, and skin and Biogeographical ancestry (BGA), called DNA phenotyping. Despite these advances, currently, there are no studies integrating the biological profile performed by forensic anthropologists, the facial approximation created by forensic artists and EVCs determined by DNA. The goal of this work was to integrate these three investigative leads to enhance the possibility of human identification. Methods: Five donated remains from Mercyhurst were studied through these approaches: reconstruction of biological profile, facial approximation and estimation of EVCs based on previous studies. Results: Our results indicated the feasibility of integrating this biological profile and EVCs data into the facial approximation developed by the forensic artist, aiming to an enhance portrait of the remains. In a second phase of this project, the accuracy of the integrated facial approximation will be assessed. Conclusions: This study pointed out the importance of an interdisciplinary approach towards the identification of human remains, as well as the combination of current methods with new technologies. Full article

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor associated with vascular disease, which is prevalent in human plasma. Two isoforms of the enzyme dimethylarginine dimethylaminohydrolase (DDAH), DDAH 1 and 2, degrade ADMA. This study investigates the association of DDAH 1 (rs669173, rs7521189) and DDAH 2 gene polymorphisms (rs805305, rs3131383) with the risk of preeclampsia (PE) comorbidity with human immunodeficiency virus (HIV) infection in pregnant women of African ancestry. A total of 405 women were enrolled in this study: 204 were PE, 201 were normotensive pregnant, and 202 were HIV positive. DNA was extracted from whole blood, and SNPs (rs669173, rs7521189, rs805305, and rs3131383) were amplified to detect single-nucleotide polymorphisms (SNPs). After PCR amplification, allelic discrimination was examined. Comparisons were conducted utilizing the Chi-squared test. Our findings indicated that preeclamptic women displayed a greater prevalence of the three variants compared to those with both PE and HIV infection. There is an association between the rs669173 and rs7521189 SNPs of the DDAH 1 gene and rs3131383 of the DDAH 2 gene, which could play a role in reducing the bioavailability of nitric oxide (NO), which affects endothelial function, leading to the development of PE in pregnant women of African ancestry. In contrast, the rs805305 variant of the DDAH 2 gene was not significantly associated with PE development. Interestingly, none of the SNPs investigated correlated with HIV infection or could be attributed to the human allelic variant influence on HIV infection outcome. Full article