Hasil untuk "Genetics"

J. Lush

P. Moran

J. Coyne

G. Hartvigsen

I. Roberts

D. Roff

R. Muhle, S. Trentacoste, I. Rapin

J. Dekkers, Frédéric Hospital

T. Whitham, W. Young, G. Martinsen et al.

C. Biémont, C. Vieira

Mingxia Wei, Jincheng Li, Tongyao You et al.

Abstract Background Cognitive impairment (CI) poses a major global health challenge. In China, neuropsychological scales, regarded as the gold standard for cognitive diagnosis, are largely inaccessible in resource-limited communities. The Mobile Eye-Tracking Application (m-ETA), which captures and quantifies eye movement features, has emerged as a promising tool for CI screening. Methods We developed a tablet-based m-ETA using a two-step approach. First, a logistic regression (LR) model was trained to discriminate dementia based on six oculometric features in a hospital cohort (N = 204), and regression analyses were conducted to validate the biological relevance of these features with Alzheimer’s Disease–related phenotypes in an exploratory dataset (N = 101). Second, the generalizability and accuracy of the LR model were externally validated in a community-based cohort (N = 433) and further evaluated in two real-world community populations (N = 2,685). Model performance was assessed using sensitivity, specificity, negative predictive value (NPV), and area under the ROC curve (AUC). Results m-ETA achieved high diagnostic accuracy for dementia (AUC = 0.99). Regression analyses confirmed that the m-ETA-derived oculometric features were significantly associated with cognitive performance, brain atrophy, and tau deposition in the exploratory dataset (all P < 0.05). m-ETA accurately detected CI (AUC = 0.80), with excellent negative predictive value for ruling out CI, and identified individuals with lower cognition performance across diverse communities. Conclusions m-ETA offers a low-cost, non-invasive, and efficient tool for large-scale CI screening, particularly suited to underserved and low-literacy communities in China.

Pooria Pakdaman, Nadereh Naderi, Narges Farshidi et al.

Abstract Background The Slit guidance Ligand 2 (SLIT2) glycoprotein is of particular interest because of its role in modulating inflammation and the progression of diseases such as atherosclerosis. This study aimed to determine whether SLIT2 polymorphisms can serve as predictive markers for coronary artery disease (CAD) development by investigating its single-nucleotide polymorphisms (SNPs). Methods In this case-control study, a total of 321 participants including 217 patients with diagnosed CAD and 104 healthy controls were recruited. Patients were divided into acute coronary syndrome (ACS) (n = 153) and stable angina pectoris (SAP) (n = 64). Allele and genotype frequency of SLIT2 SNP variants rs666088 C > T and rs16869521 A > T were determined using Polymerase Chain Reaction with Sequence-Specific Primers (PCR-SSP). Odds ratios (ORs) were reported along with their 95% confidence intervals (CIs) and P-values. Crude estimates were initially presented, followed by adjusted ORs computed using logistic regression, controlling for potential confounders including age, gender, high-density lipoprotein (HDL) levels, fasting blood sugar (FBS), and smoking status. Results The frequencies of the T allele of rs666088 were significantly higher in ACS patients compared to healthy controls, and were associated with an increased risk of ACS both before (OR = 1.5, 95% CI = 1.1–2.2, P = 0.01) and after adjustment for confounding factors (OR = 1.3, 95% CI = 1.1–1.9, P = 0.02). Moreover, analysis of ACS subgroups—myocardial infarction (MI) and unstable angina pectoris (UAP), revealed consistent results. However, the allele and genotype frequencies of rs16869521 were not significantly different between patients and controls in any disease categories. Conclusions Our study revealed that genetic polymorphism of SLIT2 (rs666088) TT genotype and T allele is the potential host genetic risk factor for ACS. Therefore, SLIT2 (rs666088) genetic variation may be considered as a biomarker for early screening and diagnosis of the disease.

Zhenxuan Gao, Lihui Feng

In the developing gut of infants, Bifidobacteria establish themselves and become one of the predominant microbial populations, playing vital roles in host health by modulating immune responses, inhibiting the growth of pathogenic bacteria, and enhancing nutrient metabolism. While Bifidobacterium strains from Western populations have been extensively studied, those derived from Chinese infants remain underexplored. Given the substantial impact of geography, diet, and host genetics on gut microbiota composition and function, strains from the Chinese population may possess unique probiotic properties with significant scientific and clinical relevance. In this study, we isolated a highly abundant clinical Bifidobacterium breve strain with intrinsically high transformation efficiency from the feces of a healthy Chinese infant. We obtained its complete genome using Oxford Nanopore sequencing. To assess its genetic tractability, we first employed two conventional double-crossover gene knockout strategies. A pyrE mutant was successfully constructed using a shuttle vector, leveraging its 5-fluoroorotic acid (5-FOA) sensitivity as a counterselection marker. To enable efficient, scarless genome editing, we developed a novel dual-plasmid system that markedly improved the selection of single-crossover events. This approach enabled robust and flexible genetic manipulation of a clinically derived B. breve strain that was previously recalcitrant to standard knockout techniques. Our work not only provides a powerful platform for dissecting the probiotic mechanisms of B. breve, but also serves as a valuable reference for the development of genetic tools applicable to other clinically relevant strains.

Margot Comel, Mouna Barat-Houari, Fanny Alkar et al.

<b>Background and Clinical Significance:</b> Familial short stature is a common reason for referral in clinical genetics. While often attributed to a single genetic cause, genetic heterogeneity can complicate diagnosis and management. This report describes a family in which three distinct pathogenic variants in <i>SHOX</i>, <i>PDE4D</i> and <i>ACAN</i> caused overlapping phenotypes of familial short stature. <b>Case Presentation:</b> Clinical, radiological and molecular data were collected retrospectively at the Reference Centre for Constitutional Bone Diseases at Montpellier University Hospital. Targeted gene panels, whole genome sequencing and Sanger sequencing were employed to identify pathogenic variants. Variant interpretation followed the guidelines of the American College of Medical Genetics. A pathogenic <i>SHOX</i> variant (c.452G>A; p.Ser151Asn) was identified in the proband and her mother, which is consistent with dyschondrosteosis. A de novo <i>PDE4D</i> variant (c.671C>T; p.Thr224Ile) was identified in a cousin presenting with syndromic acrodysostosis. An <i>ACAN</i> splice variant (c.6833-1G>A) was detected in several family members and is associated with short stature and skeletal anomalies. An individual carrying both the <i>SHOX</i> and <i>ACAN</i> variants exhibited a more severe phenotype, suggesting an additive effect. <b>Conclusions:</b> This case study highlights the importance of systematic molecular investigations in families with overlapping yet heterogeneous phenotypes. Comprehensive genetic familial analysis enables personalized care and accurate genetic counselling, particularly when multiple diagnoses coexist. A family history should not preclude molecular testing, since similar phenotypes can result from different genetic causes.

E. Bier

S. Farooqi, S. O’Rahilly

P. Wandeler, P. Hoeck, L. Keller

L. Penke, Jaap J. A. Denissen, G. Miller

Sérgio da Costa Dias, Andressa Lima de Brida, Maguintontz Cedney Jean-Baptiste et al.

The spotted-wing drosophila, <i>Drosophila suzukii</i> (Matsumura) (Diptera: Drosophilidae), is a pest that reduces the productivity of small fruits. Entomopathogenic nematodes (EPNs) and chemical insecticides can suppress this pest, but the compatibility of the two approaches together requires further examination. This laboratory study evaluated the compatibility of <i>Steinernema brazilense</i> IBCBn 06, <i>S. carpocapsae</i> IBCBn 02, <i>Heterorhabditis amazonensis</i> IBCBn 24, and <i>H. bacteriophora</i> HB with ten chemical insecticides registered for managing <i>D. suzukii</i> pupae. In the first study, most insecticides at the recommended rate did not reduce the viability (% of living infective juveniles (IJs)) of <i>S. braziliense</i> and both <i>Heterorhabditis</i> species. The viability of <i>S. carpocapsae</i> was lowered by exposure to spinetoram, malathion, abamectin, azadirachtin, deltamethrin, lambda-cyhalothrin, malathion, and spinetoram after 48 h. During infectivity bioassays, phosmet was compatible with all the EPNs, causing minimal changes in infectivity (% pupal mortality) and efficiency relative to EPN-only controls, whereas lambda-cyhalothrin generally reduced infectivity of EPNs on <i>D. suzukii</i> pupae the most, with a 53, 75, 57, and 13% reduction in infectivity efficiency among <i>H. bacteriophora, H. amazonensis, S. carpocapsae</i>, and <i>S. brazilense</i>, respectively. The second study compared pupal mortality caused by the two most compatible nematode species and five insecticides in various combinations. Both <i>Heterorhabditis</i> species caused 78–79% mortality among <i>D. suzukii</i> pupae when used alone, and were tested in combination with spinetoram, malathion, azadirachtin, phosmet, or novaluron at a one-quarter rate. Notably, <i>H. bacteriophora</i> caused 79% mortality on <i>D. suzukii</i> pupae when used alone, and 89% mortality when combined with spinetoram, showing an additive effect. Novaluron drastically reduced the number of progeny IJs when combined with <i>H. amazonensis</i> by 270 IJs and <i>H. bacteriophora</i> by 218. Any adult flies that emerged from EPN–insecticide-treated pupae had a shorter lifespan than from untreated pupae. The combined use of <i>Heterorhabditis</i> and compatible chemical insecticides was promising, except for novaluron.

Martina Weiss, Armin W. Lorenz, Christian K. Feld et al.

ABSTRACT Worldwide, humans have strongly altered river networks. Key changes resulted in modified hydromorphology, poor habitat quality and availability, migration barriers, and pollution. Restoration measures aim at mitigating anthropogenic stressors and at restoring connectivity, but the biological success of these measures is not guaranteed. Analyzing genetic diversity and metapopulation structure of target species in the river network with genetic markers can help to understand recolonization processes and to identify persisting gene flow barriers. Here, we studied the population genetic structure of the two pollution‐tolerant detritivorous isopod species, Asellus aquaticus and Proasellus coxalis, in the former heavily degraded and polluted, but now mostly restored Emscher catchment in Germany. For both species, we analyzed mitochondrial cytochrome c oxidase I (COI) gene sequences and nuclear genome‐wide single nucleotide polymorphism (SNP) data. Surprisingly, we found a strong metapopulation structure for both species with several isolated populations on a small‐scale of few kilometers, but a still high genetic diversity, especially in the COI gene. For both taxa, potentially cryptic species are known, but our SNP data showed that the mitochondrial lineages represent only one species, each, in the study area. This highlights the importance of integrating high‐resolution nuclear markers into species identification because species diversity may otherwise be overestimated. While we could identify some migration barriers and find indications for passive dispersal by birds or humans, these factors could not fully explain the local metapopulation structure, suggesting that also other drivers, such as isolation by adaptation, priority effects, or biotic interactions, play a role in shaping the population genetic structure.