Host Genetics Research Articles

Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestries

BackgroundAcute infection with hepatitis C virus (HCV) affects millions of individuals worldwide. Host genetics plays a role in spontaneous clearance of the acute infection which occurs in approximately 30% of the individuals. Common variants in GPR158, genes in the interferon lambda (IFNL) cluster, and the Major Histocompatibility complex (MHC) region have been associated with HCV clearance in populations of diverse ancestry. Fine mapping of those regions has identified some key variants and amino acids as potential causal variants but the role of rare variants in those regions and in the genome, in general, has not been explored. We aimed to detect haplotypes containing rare variants related to HCV clearance using identity-by-descent (IBD) haplotype sharing between unrelated cases-case pairs and case-controls pairs in 1,739 individuals of European ancestry and 1,869 African Americans. Additionally, we aimed to detect ancestry-specific effects in African Americans using local ancestry mapping.ResultsWe detected 2,370,341 and 1,567,748 individual pairs of IBD segments in the individuals of European ancestry and African Americans, respectively. Individuals of European descent had more segments of longer length compared to African Americans. We did not detect any significant IBD signals in the known associated or new gene regions. We also failed to detect any significant genome-wide local ancestry signals in the African Americans.ConclusionsIBD is based on sharing of haplotypes and is most powerful in populations with a shared founder or recent common ancestor. For the complex trait of HCV clearance, we used two outbred, global populations that limited our power to detect IBD associations. Overall, in these population-based samples we failed to detect rare variations associated with HCV clearance in individuals of European ancestry and African Americans, and we didn’t detect local ancestry-specific effects associated with HCV clearance in African Americans with our current sample size.

The role of plant host genetics in shaping the composition and functionality of rhizosphere microbiomes.

The plant microbiome comprises a wide range of microorganisms associated with different plant tissues. Over the past decades, significant research efforts have focused on understanding and harnessing the plant rhizosphere microbiome for optimal plant growth and health. However, while environmental factors are often the primary focus of these studies, the influence of plant genotype remains comparatively underexplored. In fact, the plant genotype influences a multitude of factors including root morphology and exudate composition, which play an integral role in shaping the rhizosphere niche. In this review, we discuss how alterations in plant host genetics could lead to differences in the assembly and diversity of the rhizosphere microbiome. Furthermore, we summarize current approaches to decipher complex plant traits and their ecological implications in host-microbiome systems and interactions.

Insomnia: the gut microbiome connection, prospects for probiotic and postbiotic therapies, and future directions.

Insomnia: the gut microbiome connection, prospects for probiotic and postbiotic therapies, and future directions.

Construction of primary chassis cells with efficient protein expression in Thermus thermophilus

BackgroundThermus thermophilus HB27 is a promising thermophilic chassis for recombinant thermostable protein production, owing to its high optimal growth temperature, which can simplify downstream processing and reduce contamination risks. However, maximizing its potential requires optimized genetic tools and host strains. Key limitations include a shortage of well-characterized strong constitutive promoters and potential degradation of recombinant proteins by proteases. To address these, we established a β-galactosidase reporter system (endogenous TTP0042) to screen for strong constitutive promoters and investigated the impact of deleting specific protease genes on protein expression.ResultsScreening of 13 endogenous promoter regions identified P0984 as exhibiting significantly 13-fold higher activity than the control promoter driving the reporter gene. Constructing a plasmid-free strain (HB27ΔpTT27) successfully minimized 270 kb of the genome; it exhibited auxotrophy for cobalamin (requiring 0.1 µg/ml AdoCbl for growth) and a slightly reduced growth rate compared to the wild-type, while its transformation efficiency remained comparable. Notably, a CRISPR-deficient precursor strain (HB27ΔIII-ABΔI-CΔCRF3) showed a significant (~ 100-fold) increase in transformation efficiency compared to the wild-type, facilitating subsequent genetic manipulations. Systematic knockout of 16 predicted non-essential protease loci was performed. Characterization revealed that deletion of TTC0264 (putative ClpY/HslU) and TTC1905 (putative HhoB) significantly reduced extracellular proteolytic activity. Iterative deletion based on phenotypic analysis led to strain DSP9 (10 protease loci deletions), which maintained robust growth and exhibited enhanced accumulation of the β-galactosidase reporter protein compared to the parental strains.ConclusionsThis study provides foundational advancements for T. thermophilus HB27 chassis development, and genetic tools represent valuable resources for optimizing T. thermophilus as a platform for heterologous thermostable protein production and ideas for antibiotic-free systems.

Alcohol, Aging, and the Gut Microbiome: Intersections of Immunity, Barrier Dysfunction, and Disease.

Alcohol, Aging, and the Gut Microbiome: Intersections of Immunity, Barrier Dysfunction, and Disease.

Nutrological, microbiological and extracellular vesicle evidence in the modulation and control of inflammatory bowel disease symptoms: a systematic review

Introduction: Inflammatory bowel diseases (IBD) have an increasing incidence and prevalence, such as Crohn's disease (CD) and ulcerative colitis (UC). Gut dysbiosis is affected by host genetics, nutrition, antibiotics, and inflammation, and is associated with the development of IBD, which can be attributed to impaired miRNA expression functions. Micro and macronutrient deficiencies and overabundance of calories and macronutrients trigger inflammatory processes and susceptibility to infections. Objective: To present the nutrological, microbiological, and extracellular vesicle (exosome-microRNAs) evidence in the modulation and control of symptoms of inflammatory bowel diseases. Methods: The systematic review rules of the PRISMA Platform were followed. The literary search process was carried out from March to May 2025 in the Web of Science, Scopus, Embase, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 189 articles were found. A total of 27 articles were fully evaluated and 21 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 21 studies with a high risk of bias and 29 studies that did not meet GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2=85.7%>50%. It was concluded that miRNAs are important regulators of cellular function and homeostasis, and their abnormal activity has been demonstrated in several diseases, including IBD. Thus, new treatment options could be developed to alter imbalances in miRNA expression. miRNAs affect the intestinal barrier and inflammatory reactions through several pathological mechanisms. The use of miRNAs as biomarkers and therapeutic targets may help monitor IBD treatment and support the development of new, more individualized therapies that minimize common side effects. Extracellular vesicles may attenuate the inflammatory response by inhibiting the TLR4-NF-κB signaling pathway and activating the NLRP3 inflammasome. Dietary manipulation of microRNAs through prebiotics and probiotics may selectively manipulate the gut microbiota, with the bacterium Faecalibacterium prausnitzii being prevalent in healthy adults, being beneficial and producing short-chain fatty acids, such as butyrate, which serves as an energy source for intestinal epithelial cells and induces protective regulatory immune responses.

A pathogen of good taste: genetics of a bacterial host jump of the plant pathogen Xylella fastidiosa from coffee to wine grapes.

When pathogens are repeatedly introduced into new environments, host jumps may occur into naïve taxa. Given the magnitude of the global plant trade, this process can lead to frequent disease emergence as interactions between previously isolated pathogens and new plant hosts become possible. Xylella fastidiosa is a recurring nuisance. This bacterial pathogen has recently emerged in novel geographic locations infecting a breadth of host plants. An introduction of X. fastidiosa subsp. fastidiosa from Central America to the USA several hundred years ago has since been the source of outbreaks across the globe. In the USA, particularly in California, the introduced bacterium is frequently found in European grapevine (Vitis vinifera). In this study, we demonstrated that the introduced strains do not persistently infect Coffea arabica. Furthermore, we did not observe an overall increase in the virulence of the introduced strains towards coffee, indicating a lack of hypervirulence. Then, using X. fastidiosa subsp. fastidiosa whole-genome sequences, 15 from the source region of Costa Rica and 289 from the introduced clade, we tested for traces of adaptation to grapevines. We found both genes and SNPs that are associated with the host shift to grapevines. These results support the hypothesis that a host jump with genetic adaptation occurred following the introduction of the pathogen into the USA.

Evolutionary Dynamics of Codon Usage Bias in Tomato Spotted Wilt Virus: Insights into Viral Adaptation and Host Interactions

Tomato spotted wilt virus (TSWV), belonging to the genus Orthotospovirus, is a significant pathogen through its infection of economically vital crops including tomato, tobacco, pepper, and other species worldwide. Given its substantial influence on the agricultural industry, in-depth research on TSWV is of great necessity. Several studies have been conducted on the dinucleotide preference of TSWV previously; however, the information regarding codon usage bias (CUB) and the virus’s adaptive evolution remains inconclusive. Here, a thorough analysis of TSWV was performed by utilizing five protein-coding sequences in order to investigate the characteristics of CUB. It has been observed that the TSWV protein-coding sequences are AU-rich, and codons ending with A or U are also preferred in these sequences. A consistently stable and preserved genomic composition characterized by a lower codon usage preference was also observed. Principal Component Analysis (PCA), neutrality analysis, and ENC-plot indicated that, in comparison to mutational pressure, natural selection has a more dominant influence on the CUB of TSWV. The codon adaptation index (CAI) demonstrated a more significant correlation between TSWV and Nicotiana tabacum. Meanwhile, the relative codon deoptimization index (RCDI) indicated a stronger correlation between TSWV and Solanum lycopersicum. This study is the first to systematically characterize the CUB of TSWV based on its protein-coding sequences, providing critical insights into viral genetic diversity, evolution mechanisms, and host adaptation. The findings advance understanding of plant-virus coevolution and inform virus-resistant crop breeding and antiviral strategies.

HIV infection and exposure is associated with increased cariogenic taxa, reduced taxonomic turnover, and homogenized spatial differentiation for the supragingival microbiome

BackgroundThe oral microbiome consists of distinct microbial communities that colonize various ecological niches within the oral cavity, the composition of which are influenced by nutrient and substrate availability, host genetics, diet, behavior, age, and other diverse host and environmental factors. Unlike other densely populated human-associated microbial ecosystems (e.g., gut, urogenital), the oral microbiome is directly and frequently exposed to external influences, contributing to its relatively lower stability over time. In individuals with compromised immunity, such as those living with HIV, the composition and stability of the oral microbiome may be especially vulnerable to disruption. Cross-sectional studies of the oral microbiome in children living with HIV capture a glimpse of this temporal dynamism, yet a full appreciation of the relative stability, robusticity, and spatial structure of the oral environment is necessary to understand the role of microbial communities in promoting health or disease in the context of HIV. Here, we investigate the spatial and temporal stability of the oral microbiome over three sampling time points in the context of HIV infection and exposure. Individual teeth were sampled from a cohort of 565 Nigerian children with varying levels of tooth decay severity (i.e., caries disease). We collected 1960 supragingival plaque samples and characterized the oral microbiome using a metataxonomic approach targeting an approximately 478 bp region of the bacterial rpoC gene.ResultsBoth HIV infection and exposure have significant, if subtle, effects on the stability of the supragingival plaque microbiome. Specifically, we observed (1) a slight but significant reduction in taxonomic turnover among HIV-exposed and infected children; (2) an association between HIV infection and a more homogenized oral community across the anterior and posterior dentition in children living with HIV; and (3) a relationship between impaired immunity, lower taxonomic turnover over time, and an elevated frequency of cariogenic taxa, including Streptococcus mutans, in children living with HIV.ConclusionsDespite the influence of various contributing factors, we observe an effect of HIV status on both the temporal and spatial stability of the oral microbiome. Specifically, the results presented here indicate that the oral microbiome shows less community change over time in children living with or exposed to HIV, which we hypothesize may be linked to a reduced capacity to adapt to environmental changes. The observed taxonomic rigidity among children living with HIV may signal community dysfunction, potentially leading to a higher incidence of oral diseases, including caries, in this cohort.-7X2s65mtVxV_hGnFfTU7iVideo

Subgingival microbiota and genetic factors (A-2570G, A896G, and C1196T TLR4 polymorphisms) as periodontal disease determinants.

Subgingival microbiota play an important role in maintaining oral health. Subgingival dysbiosis leads to the aggregation of highly pathogenic bacteria, and the host's genetics modulates the innate immune response. The interaction between these two factors plays an important role in the aggravation of periodontitis. Therefore, evaluating the association between the TLR-4 polymorphisms and subgingival microbiota in patients with periodontitis is necessary. We included 58 cases with periodontitis and 53 controls without periodontitis in this study. A896G, A-2570G, and C1196T polymorphisms of the TLR4 gene were determined by the polymerase chain reaction and restriction fragment length polymorphism technique. The DNA-DNA checkerboard hybridization technique was used for the identification and quantification of 18 bacterial species of subgingival plaque. Cutibacterium acnes occurred in greater number and frequency than other bacterial species ( 1.32 E + 05) in individuals with periodontitis. Patients with C. acnes had a higher risk [odds ratio (OR)= 3.82 (95% confidence interval (CI): 1.37-10.3)] of developing periodontitis (p < 0.05), as did those with orange and red complex bacteria (Treponema denticola, Tannerella forsythia, Porphyromonas gingivalis, Prevotella nigrescens, Prevotella intermedia, Fusobacterium periodonticum, Fusobacterium nucleatum, Eubacterium nodatum, and Campylobacter rectus). The A/G genotype of SNP -2570 of the TLR4 gene was identified as a risk factor for the development of periodontitis [OR = 2.28 (95% CI: 1.04-5.00)]. Furthermore, there was an antagonistic biological effect of the presence of bacteria such as Capnocytophaga gingivalis [OR = 0.44 (95% CI: 0.20-1.96)] and C. rectus [OR = 0.39 (95% CI: 0.18-0.87)] (p < 0.05). The A/G genotype of SNP-2570 was correlated with greater clinical attachment loss and periodontal pocket depth. The agonistic or antagonistic biological effect of each bacterial species depends on the genotype present in each individual and the destruction processes of dental support tissues.

Confirmation of HLA-II associations with TB susceptibility in admixed African samples.

Previously, the International Tuberculosis Host Genetics Consortium (ITHGC) demonstrated the power of large-scale GWAS analysis across diverse ancestries in identifying tuberculosis (TB) susceptibility loci (Schurz et al., 2024). Despite identifying a significant genetic correlate in the human leukocyte antigen (HLA)-II region, this association did not replicate in the African ancestry-specific analysis, due to small sample size and the inclusion of admixed samples. Our study aimed to build upon the findings from the ITHGC and identify TB susceptibility loci in an admixed South African cohort using the local ancestry allelic adjusted association (LAAA) model. We identified a suggestive association peak (rs3117230, p-value = 5.292 × 10-6, OR = 0.437, SE = 0.182) in the HLA-DPB1 gene originating from KhoeSan ancestry. These findings extend the work of the ITHGC, underscore the need for innovative strategies in studying complex admixed populations, and confirm the role of the HLA-II region in TB susceptibility in admixed South African samples.

Confirmation of HLA-II associations with TB susceptibility in admixed African samples

Previously, the International Tuberculosis Host Genetics Consortium (ITHGC) demonstrated the power of large-scale GWAS analysis across diverse ancestries in identifying tuberculosis (TB) susceptibility loci (Schurz et al., 2024). Despite identifying a significant genetic correlate in the human leukocyte antigen (HLA)-II region, this association did not replicate in the African ancestry-specific analysis, due to small sample size and the inclusion of admixed samples. Our study aimed to build upon the findings from the ITHGC and identify TB susceptibility loci in an admixed South African cohort using the local ancestry allelic adjusted association (LAAA) model. We identified a suggestive association peak (rs3117230, p-value = 5.292 × 10-6, OR = 0.437, SE = 0.182) in the HLA-DPB1 gene originating from KhoeSan ancestry. These findings extend the work of the ITHGC, underscore the need for innovative strategies in studying complex admixed populations, and confirm the role of the HLA-II region in TB susceptibility in admixed South African samples.

Confirmation of HLA-II associations with TB susceptibility in admixed African samples

Previously, the International Tuberculosis Host Genetics Consortium (ITHGC) demonstrated the power of large-scale GWAS analysis across diverse ancestries in identifying tuberculosis (TB) susceptibility loci (Schurz et al., 2024). Despite identifying a significant genetic correlate in the human leukocyte antigen (HLA)-II region, this association did not replicate in the African ancestry-specific analysis, due to small sample size and the inclusion of admixed samples. Our study aimed to build upon the findings from the ITHGC and identify TB susceptibility loci in an admixed South African cohort using the local ancestry allelic adjusted association (LAAA) model. We identified a suggestive association peak (rs3117230, p-value = 5.292 × 10-6, OR = 0.437, SE = 0.182) in the HLA-DPB1 gene originating from KhoeSan ancestry. These findings extend the work of the ITHGC, underscore the need for innovative strategies in studying complex admixed populations, and confirm the role of the HLA-II region in TB susceptibility in admixed South African samples.

Inoculation of Maize Leaves with the Bacterial Foliar Pathogen Clavibacter nebraskensis.

Maize significantly contributes to food and fuel production. Yields can be reduced due to foliar diseases, which reduce photosynthetic leaf area. The bacterial foliar disease Goss's wilt (caused by Clavibacter nebraskensis) can cause significant yield losses in susceptible maize varieties. C. nebraskensis can infect leaves through wounds and colonize the vascular tissue of the leaf. We present a protocol that replicates this process with the use of a "clapper" with pins on one end to create wounds and a sponge soaked in inoculum on the other end, which allows for efficient field inoculations of maize leaves. Disease severity is then rated on a percentage scale multiple times over the season to generate an area under disease progress curve (AUDPC). Genetic host resistance is one of the most effective forms of foliar disease control in maize, as there are few effective forms of chemical control for bacterial diseases that affect maize. Screening for resistance in diverse germplasm, or for fine mapping a specific resistance gene, requires inoculating large populations in the field for obtaining phenotypic data. Our high-throughput protocol allows for large-scale disease evaluations and is useful for finding forms of genetic resistance or to understand plant-pathogen interactions of bacterial foliar pathogens.

Polysaccharide synthesis operon modulates Rickettsia-endothelial cell interactions.

Pathogenic Rickettsia species target vascular endothelial cells and cause systemic vasculitis. As obligate intracellular bacterial pathogens, Rickettsia must secure nutritional resources within the cytoplasm of endothelial cells while simultaneously subverting the innate immune defense system. With advances in rickettsial and host genetics, recent studies have identified novel molecular mechanisms involved in the complex interactions between Rickettsia and endothelial cells. However, it remains unclear how Rickettsia shields pathogen-derived immune stimulants, such as lipopolysaccharides (LPS) and peptidoglycan fragments, from immune recognition during intracellular replication. Prior work described two Rickettsia conorii variants with kkaebi transposon insertions in the polysaccharide synthesis operon (pso). Biochemical and immunological analyses revealed that pso is responsible for the biosynthesis of O-antigen (O-Ag) and the proper assembly of surface proteins. In the present work, we document that pso variant HK2 exhibits reduced capacities to adhere to and invade microvascular endothelial cells. Despite the low intracellular abundance, HK2 induced significantly higher levels of proinflammatory cytokines and chemokines, leading to premature cell death. Notably, HK2 exhibited defective intracellular survival in bone marrow-derived macrophages. This inability to dampen endothelial cell-mediated immune stimulation and resist macrophage-induced bactericidal activities resulted in the rapid elimination of viable Rickettsia in the mouse model of spotted fever. Further, when tested as a live-attenuated vaccine, HK2 elicited robust protective immunity against lethal spotted fever pathogenesis. Our work highlights the crucial role of pso in enabling Rickettsia to evade immune surveillance during intracellular replication within endothelial cells, ultimately delaying pathogen-induced programmed cell death and escaping immune defense mechanisms.

Invited review: Interplay of rumen microbiome and the cattle host in modulating feed efficiency and methane emissions.

Given that the majority of energy and protein supplied to cattle arises as a result of ruminal fermentation, the rumen microbiome plays a key role in determining host feed efficiency and methane (CH4) emissions. Some reports suggest that a less diverse rumen microbiome is associated with improved feed efficiency, whereas other studies suggest that microbial diversity does not differ between low- and high-efficiency cattle of the same breed, fed identical diets. Although reducing enteric CH4 emissions offers a dual benefit in terms of improved feed efficiency and a reduced environmental footprint, recent findings indicate that these outcomes are not always consistent in ruminants. The composition of the rumen microbiome is mainly determined by diet but is also influenced by host genetics and physiological parameters such as rumen volume, rate of passage, and rumination. Reduced microbial diversity may impair the ability of cattle to adapt to frequent changes in diet and the environment. Hydrogen exchange and capture are the energetic foundation of the rumen microbiome, and considerable resources have been invested in developing additives that redirect hydrogen flow toward alternative sinks and away from the reduction of CO2 to CH4. These additives reduce enteric CH4 emissions by 30% to 80%, yet the anticipated gains in feed efficiency remain inconsistent. Strategies to improve the feed efficiency of cattle production must consider the multifaceted interactions among the host, rumen microbiome, and diet to ensure the sustainable intensification of cattle production while maintaining the social license for milk and meat production.

Study on the correlation between BRCA1 gene polymorphism and hrHPV infection in cervical precancerous lesions.

Study on the correlation between BRCA1 gene polymorphism and hrHPV infection in cervical precancerous lesions.

Rescue of a unique ovine parainfluenza virus type 3 strain via Red/ET assembly.

Rescue of a unique ovine parainfluenza virus type 3 strain via Red/ET assembly.

Genetic diversity and host specificity of Blastocystis in yaks in Xinjiang, northwest China.

Genetic diversity and host specificity of Blastocystis in yaks in Xinjiang, northwest China.

Meta-analysis reveals the processes and conditions of using biochar to control antibiotic resistance genes in soil.

Meta-analysis reveals the processes and conditions of using biochar to control antibiotic resistance genes in soil.