Allele Of Gene Research Articles

Impact of HLA Class I Antigen, Killer Inhibitory Receptor, and FCGR3A Genotypes on Breast Cancer Susceptibility and Tumor Stage.

The identification in breast cancer (BC) of novel genetic biomarkers regulating natural killer (NK) cell function, including the HLA, KIR, and CD16A (FCGR3A), may be still a challenge. We aimed to evaluate whether the combined effect of these polymorphisms has an impact on BC susceptibility and progression. 47 BC Italian patients and healthy individuals (39 females and 66 males/ females) were genotyped by Sanger sequencing (HLA-C exon 2-4 and FCGR3A- 158V/F, 48L/R/H) and PCR-SSP typing (KIR genes). HLA-C gene allele analysis showed the group C1, with HLA-C*07:02:01 allele, to be significantly associated with tumor progression (16.7% vs. 4.0%, p=0.04, OR=4.867), and instead, group C2, with HLA-C*05:01:01, was protective against disease susceptibility (0.0% vs. 7.2%, p=0.019, OR=0.087). In addition, we highlighted a significant reduction of the KIR2DS4ins in BC patients (pcorr.=0.022) and an increased combined presence of KIR2DL1 and KIR2DS1 genes in advanced BC patients compared to earlier stages (66.7% vs. 19.2%, p=0.002). The concurrent lack of KIR2DL2 and KIR2DS4 genes in the presence of HLA-C2 alleles was significantly associated with increased susceptibility to BC (p=0.012, OR=5.020) or with lymph node involvement (p=0.008, OR=6.375). Lastly, we identified different combinations of the FCGR3A-48/158 variants and KIR genes in BC patients compared to controls. Our findings suggest that in the development of BC probably exists a disorder of the NK innate immunity influenced by KIR/HLA-C gene content and FCGR3A-158 polymorphisms and that the combined analysis of these biomarkers might help predict genetic risk scores for tailored screening of BC patients in therapy.

Study of HSP70 Gene and Relationship to Milk Productivity and Fat Ratio Holstein Cows

The study was conducted on 75 Holstein cows imported from Germany to determine the chi-square value, the breeding value, the additive and dominance effect, and the effect of the allele of the HSP70 gene on the variation of total milk production and fat ratio. The HSP70 gene was divided into three bands, each with a length of 922, 935 and 932 bp. Molecular analysis of the gene shows the presence of 12-point mutations distributed in three primers (T825C, G856A, G937A, A1135G, G1185C, G1753A, C1867T, A2017G, C2548T, G2572T, G2688C and T2734C). Mutation T825C changed the amino acid Ata to Lie, and mutation G856A changed the amino acid Aca. to Thr. The result showed that the chi-square value was significant in the mutations (C1867T, A2017G and G2688C) reached (4.25, 3.90 and 4.16). The higher milk production in the CT genotype of the C1867T mutation was 5442.7 kg/season, the higher breeding value, dominance deviation, additive and dominance variance (652.3, 1460, 726856 and 235183) respectively for total milk production. The higher ratio of fat in the CT genotype of the C2548T mutation was (5.04%), and the higher breeding value, dominance deviation, additive and dominance variance (1.30, 1.70, 0.576 and 0.0793), respectively for the ratio of fat.

STUDYING THE DIVERSITY OF LENTIL VARIETIES BY ALLELES OF THE EARLY FLOWERING GENE LcELF3 USING MOLECULAR MARKERS

Lentils are one of the most widespread leguminous crops in the world and now Kazakhstan is also experiencing a significant expansion of acreage. Howev-er, late sowing is unacceptable for this crop, since in this case the photoperiod effect and drought lead to loss of crop samples if the flowering period of lentil plants is not optimized. The genes controlling early flowering (EFL3) are associ-ated with the rate of growth and the beginning of flowering and are independent of the length of daylight. In this study, the presence of the early flowering gene LcELF3 was analyzed in 76 collection samples of lentils. As a result of PCR am-plification and sequencing of the LcELF3 gene using the Sanger method, genetic polymorphism was detected and codominant SNP (Single Nucleotide Polymor phism) markers were developed. Further testing of collection samples of lentils by ASQ genotyping allowed us to identify 36 samples with homozygous geno-type aa (late flowering) and 40 samples with homozygous genotype bb (earlier flowering). The use of factor analysis of the productivity elements of lentil sam-ples bearing favorable bb alleles of the early flowering gene LcELF3 made it pos sible to conduct a visual analysis for the studied years. Thus, using the example of lentils, the possibility of sampling samples containing favorable bb alleles of the LcEFL3 gene, controlling early flowering, which are necessary to increase its yield in conditions of prolonged spring and short summer season in the dry steppe zone of Northern Kazakhstan, is shown.

Tracing the color: quantitative trait loci analysis reveals new insights into red-flesh pigmentation in apple (Malus domestica).

Red-flesh color development in apple fruit is known to depend upon a particular allele of the MdMYB10 gene. While the anthocyanin metabolic pathway is well characterized, current genetic models do not explain the observed variations in red-flesh pigmentation intensity. Previous studies focused on total anthocyanin content as a phenotypic trait to characterize overall flesh color. While this approach led to a global understanding of the genetic mechanisms involved in color expression, it is essential to adopt a more quantitative approach, by analyzing the variations of other phenolic compound classes, in order to better understand the molecular mechanisms involved in the subtle flesh color variation and distribution. In this study, we performed pedigree-based quantitative trait loci (QTL) mapping, using the FlexQTL™ software, to decipher the genetic determinism of red-flesh color in five F1 inter-connected families segregating for the red-flesh trait. A total of 452 genotypes were evaluated for flesh color and phenolic profiles during 3years (2021-2023). We identified a total of 24 QTLs for flesh color intensity and phenolic compound profiles. Six QTLs were detected for red-flesh color on LG1, LG2, LG8, LG9, LG11, and LG16. Several genes identified in QTL confidence intervals were related to anthocyanin metabolism. Further analyses allowed us to propose a model in which the competition between anthocyanins and flavan-3-ols (monomer and oligomer) end-products is decisive for red-flesh color development. In this model, alleles favorable to high red-flesh color intensity can be inherited from both white-flesh and red-flesh parents.

The cacao gene atlas: a transcriptome developmental atlas reveals highly tissue-specific and dynamically-regulated gene networks in Theobroma cacao L

BackgroundTheobroma cacao, the cocoa tree, is a tropical crop grown for its highly valuable cocoa solids and fat which are the basis of a 200-billion-dollar annual chocolate industry. However, the long generation time and difficulties associated with breeding a tropical tree crop have limited the progress of breeders to develop high-yielding disease-resistant varieties. Development of marker-assisted breeding methods for cacao requires discovery of genomic regions and specific alleles of genes encoding important traits of interest. To accelerate gene discovery, we developed a gene atlas composed of a large dataset of replicated transcriptomes with the long-term goal of progressing breeding towards developing high-yielding elite varieties of cacao.ResultsWe describe the creation of the Cacao Transcriptome Atlas, its global characterization and define sets of genes co-regulated in highly organ- and temporally-specific manners. RNAs were extracted and transcriptomes sequenced from 123 different tissues and stages of development representing major organs and developmental stages of the cacao lifecycle. In addition, several experimental treatments and time courses were performed to measure gene expression in tissues responding to biotic and abiotic stressors. Samples were collected in replicates (3–5) to enable statistical analysis of gene expression levels for a total of 390 transcriptomes. To promote wide use of these data, all raw sequencing data, expression read mapping matrices, scripts, and other information used to create the resource are freely available online. We verified our atlas by analyzing the expression of genes with known functions and expression patterns in Arabidopsis (ACT7, LEA19, AGL16, TIP13, LHY, MYB2) and found their expression profiles to be generally similar between both species. We also successfully identified tissue-specific genes at two thresholds in many tissue types represented and a set of genes highly conserved across all tissues.ConclusionThe Cacao Gene Atlas consists of a gene expression browser with graphical user interface and open access to raw sequencing data files as well as the unnormalized and CPM normalized read count data mapped to several cacao genomes. The gene atlas is a publicly available resource to allow rapid mining of cacao gene expression profiles. We hope this resource will be used to help accelerate the discovery of important genes for key cacao traits such as disease resistance and contribute to the breeding of elite varieties to help farmers increase yields.

Polymorphism of growth hormone (GH/HaeIII) gene and its association with the performance of merino cross rams

Merino cross sheep (75% Merino × 25% Garut) are introduced by the government of Indonesia for meat production purposes. The present study aimed to determine the polymorphism in the exon 2 region of the growth hormone (GH) gene (422 bp) in Merino cross rams using the PCR-RFLP technique and to analyze its relationship with body weight and body measurements of the rams. A total of 145 rams aged one-year-old with an average body weight of 29.08 ± 7.96 kg from the breeding station in West Java, Indonesia were considered as the experimental animals. It was indicated that a missense mutation of c.55G > A (p.G19S) was detected in the target sequence of the GH gene in Merino cross rams. The PCR-RFLP analysis in the GH gene of Merino cross with HaeIII restriction enzyme (GH/HaeIII) was observed in a moderate category with a polymorphic informative content (PIC) value of 0.22. Therefore, the G allele was more frequent than the A allele (0.85 versus 0.15). Furthermore, the genotype AA was not present among the sheep that were part of the study. However, the polymorphism of p.G19S was found to have no significant association with birth weight and body measurements in one-year-old Merino cross sheep. However, the GH/HaeIII gene in Merino cross rams exhibited polymorphism, primarily with two genotypes: GG (wildtype) and GA (carrier). The G allele was identified as the dominant allele in the ovine GH gene, occurring with a frequency of 0.85. Importantly, the polymorphism of the GH/HaeIII gene was significantly linked to birth weight and chest depth in one-year-old Merino cross rams. These findings provide preliminary insights that could potentially aid in the early stages of molecular selection for Indonesian Merino cross sheep.

The Impact of RHT Gene Alleles on the Yield of Spring Wheat Under Drought Conditions

The Impact of RHT Gene Alleles on the Yield of Spring Wheat Under Drought Conditions

P67 gene alleles sequence analysis reveals Theileria parva parasites associated with East Coast fever and Corridor disease in buffalo from Zambia

Theileriosis caused by Theileria parva infections is responsible for high cattle mortalities in Zambia. Although infected buffalo are a risk to cattle, the characterization of T. parva parasites occurring in this host in Zambia has not been reported. Furthermore, considering the advances in the development of a p67 subunit vaccine, the knowledge of p67 genetic and antigenic diversity in both cattle and buffalo associated T. parva is crucial. Therefore, blood samples from buffalo (n=43) from Central, Eastern and Southern provinces, and cattle (n=834) from Central, Copperbelt, Eastern, Lusaka, and Southern provinces, were tested for T. parva infection and the parasites characterized by sequencing the gene encoding the p67 antigen. About 76.7 % of buffalo and 19.3 % of cattle samples were PCR positive for T. parva. Three of the four known p67 allele types (1, 2 and 3) were identified in parasites from buffalo, of which two (allele types 2 and 3) are associated with T. parva parasites responsible for Corridor disease. Only allele type 1, associated with East Coast fever, was identified from cattle samples, consistent with previous reports from Zambia. Phylogenetic analysis revealed segregation between allele type 1 sequences from cattle and buffalo samples as they grouped separately within the same sub-clade. The high occurrence of T. parva infection in buffalo samples investigated demonstrates the risk of Corridor disease infection, or even outbreaks, should naïve cattle co-graze with infected buffalo in the presence of the tick vector. In view of a subunit vaccine, the antigenic diversity in buffalo associated T. parva should be considered to ensure broad protection. The current disease control measures in Zambia may require re-evaluation to ensure that cattle are protected against buffalo-derived T. parva infections. Parasite stocks used in ‘infection and treatment’ immunization in Zambia, have not been evaluated for protection against buffalo-derived T. parva parasites currently circulating in the buffalo population.

Comparing the Yield of Recombinant Human Factor VII Protein Expressed by the rDNA-Promoter with the CMV-Promoter in Iranian Lizard Leishmania.

Iranian Lizard Leishmania (I.L.L) is a nonpathogenic Leishmania strain. Due to its advantages, several recombinant proteins have been produced in this host. However, I.L.L shows a lower yield of recombinant protein expression compared to other commercial hosts. Considering the role of protease enzymes in protein digestion, we selected cysteine protease B (CPB) to investigate its impact on recombinant protein yield in I.L.L. we generated gene knockouts by utilizing homologous recombination (HR) and CRISPR methods. To assess the efficacy of the designed construct, we compared the yield of recombinant human factor VII (rhFVII) production between cells transfected with the pLEXSY-hyg2-FVII vector and the CMV-promoter-based construct (pF7cmvneo). The knockout of a single CPB gene allele through the HR method or the complete knockout of all alleles through the CRISPR method led to cell death. This outcome suggests that even the deletion of a single CPB gene allele diminishes the protein to a level insufficient for the survival of I.L.L, indicating a critical dependency on the presence of this protein for the organism's viability. rhFVII exhibited a greater expression yield with the pLEXSY construct compared to the pF7cmvneo construct in I.L.L. The lower expression rate of pF7cmvneo may be influenced by epigenetic factors related to the CPC gene or the RNA polymerase used for the expression of that promoter. Therefore, considering alternative integration targets for CMV-promoter-based constructs and incorporating UTR sequences of I.L.L high-expression proteins in the vector may enhance recombinant protein expression rates.

Deletion of Trps1 regulatory elements recapitulates postnatal hip joint abnormalities and growth retardation of Trichorhinophalangeal syndrome in mice.

Trichorhinophalangeal syndrome (TRPS) is a genetic disorder caused by point mutations or deletions in the gene-encoding transcription factor TRPS1. TRPS patients display a range of skeletal dysplasias, including reduced jaw size, short stature, and a cone-shaped digit epiphysis. Certain TRPS patients experience early onset coxarthrosis that leads to a devastating drop in their daily activities. The etiologies of congenital skeletal abnormalities of TRPS were revealed through the analysis of Trps1 mutant mouse strains. However, early postnatal lethality in Trps1 knockout mice has hampered the study of postnatal TRPS pathology. Here, through epigenomic analysis we identified two previously uncharacterized candidate gene regulatory regions in the first intron of Trps1. We deleted these regions, either individually or simultaneously, and examined their effects on skeletal morphogenesis. Animals that were deleted individually for either region displayed only modest phenotypes. In contrast, the Trps1Δint/Δint mouse strain with simultaneous deletion of both genomic regions exhibit postnatal growth retardation. This strain displayed delayed secondary ossification center formation in the long bones and misshaped hip joint development that resulted in acetabular dysplasia. Reducing one allele of the Trps1 gene in Trps1Δint mice resulted in medial patellar dislocation that has been observed in some patients with TRPS. Our novel Trps1 hypomorphic strain recapitulates many postnatal pathologies observed in human TRPS patients, thus positioning this strain as a useful animal model to study postnatal TRPS pathogenesis. Our observations also suggest that Trps1 gene expression is regulated through several regulatory elements, thus guaranteeing robust expression maintenance in skeletal cells.

The ABCA1 gene polymorphisms rs1800977 and rs2230806 are differentially associated with the risk for myocardial infarction in Slovenian subjects with type 2 diabetes mellitus

BackgroundThe adenosine triphosphate-binding cassette transporter A1 (ABCA1) is closely linked to various aspects of the regulation of whole-body cholesterol metabolism and atherosclerosis formation. The object of the study was to investigate the association between rs1800977 and rs2230806 polymorphisms in the ABCA1 gene and myocardial infarction (MI) in Slovenian subjects with type 2 diabetes mellitus (T2DM). Methods1590 T2DM patients (484 subjects with MI and 1106 controls) were included in this retrospective cross-sectional case–control study. After genotyping, Pearson χ2 test was used to compare the distribution of genotypes and alleles among the two groups. Logistic regression analysis adjusted for several risk factors for MI was performed. ResultsGenotype distribution showed significant association with MI in T2DM subjects for both selected polymorphisms in ABCA1 gene (p = 0.009 for rs2230806 and p = 0.042 for rs1800977). After applying corrections for confounding variables like age, waist circumference, diastolic blood pressure, serum high-density lipoprotein levels, gender and smoking several genetic models still showed significant associations with MI (dominant model for rs2230806 and dominant, overdominant and co-dominant for rs1800977). ConclusionOur study showed that presence of the T allele of the rs2230806 ABCA1 gene is associated with higher risk of MI, while the A allele of the rs1800977 conferred protection against MI in Slovenian T2DM subjects.

Association of insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme gene (ACE) with Parkinson’s disease and factors risk in eastern Algeria: case–control study

BackgroundThis study aimed to explore the relationship between Parkinson’s disease and insertion/deletion polymorphism (I/D) of the angiotensin-converting enzyme gene (ACE) and to highlight the related risk factors within Eastern Algerian population. A total of 262 individuals were recruited, including 100 PD patients and 162 controls. Polymerase chain reaction technique was employed to determine the ACE polymorphism genotype of each participant. Logistic regression analysis was conducted to examine factors potentially contributing to Parkinson’s disease.ResultsThe mean age of onset of Parkinson’s disease in the patient group was 56.18 ±12.99\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm 12.99$$\\end{document}. The results revealed that the D allele of the angiotensin-converting enzyme gene and the DD genotype were most prevalent in both patients and controls. However, there were no significant differences in the genotype and allele frequencies of the I/D polymorphism of the angiotensin-converting enzyme gene between patients and healthy subjects. Cardiovascular disease, diabetes and profession were identified as potential risk factors for Parkinson’s disease.ConclusionThe obtained data indicated no correlation between the angiotensin-converting enzyme I/D gene polymorphism and Parkinson’s disease in our research cohort. Multiple logistic regression analysis revealed that cardiovascular disease, diabetes and profession were possible risk factors for Parkinson’s disease.

A novel insertional allele of the CG18135 gene is associated with severe mutant phenotypes in Drosophila melanogaster.

Drosophila melanogaster has been at the forefront of genetic studies and biochemical modeling for over a century. Yet, the functions of many genes are still unknown, mainly because no phenotypic data are available. Herein, we present the first evidence data regarding the particular molecular and other quantifiable phenotypes, such as viability and anatomical anomalies, induced by a novel P{lacW} insertional mutant allele of the CG18135 gene. So far, the CG18135 functions have only been theorized based on electronic annotation and presumptive associations inferred upon high-throughput proteomics or RNA sequencing experiments. The descendants of individuals harboring the CG18135 P{lacW}CG18135 allele were scored in order to assess mutant embryonic, larval, and pupal viability versus Canton Special (CantonS). Our results revealed that the homozygous CG18135 P{lacW}CG18135 /CG18135 P{lacW}CG18135 genotype determines significant lethality both at the inception of the larval stage and during pupal development. The very few imago escapers that either breach or fully exit the puparium exhibit specific eye depigmentation, wing abnormal unfolding, strong locomotor impairment with apparent spasmodic leg movements, and their maximum lifespan is shorter than 2days. Using the quantitative real-time PCR (qRT-PCR) method, we found that CG18135 is upregulated in male flies, but an unexpected gene upregulation was also detected in heterozygous mutants compared to wild-type flies, probably because of regulatory perturbations induced by the P{lacW} transposon. Our work provides the first phenotypic evidence for the essential role of CG18135, a scenario in accordance with the putative role of this gene in carbohydrate-binding processes.

Association of single nucleotide genetic polymorphisms of vitamin D receptor and calcium-sensitive receptor with calcium-containing kidney stones in Chinese Dai populations: a prospective multi-center study.

To evaluate the association between vitamin D receptor (VDRs) and calcium-sensitive receptor (CaSR) gene polymorphisms and calcium-containing kidney stones (CCKS) in Dai populations. A total of 160 CCKS patients and 87 healthy controls were included in this study. CCKS was confirmed using urological computed tomography (CT), plain abdominal radiograph, or surgical lithotomy. Stone samples obtained during surgery were analyzed using infrared spectroscopy. Venous blood and 24-h urine samples were collected and analyzed using Sanger sequencing and high-performance liquid chromatography, respectively. Genetic variants in the VDR gene (rs7975232, rs2228570, rs731236, and rs1544410) and CaSR gene (rs7652589, rs1801725, and rs1042636) were identified through sequence analysis. Analysis of genotype and allele frequencies revealed that the rs7975232 polymorphism in the VDR gene and the rs7652589 allele in the CaSR gene were significantly associated with CCKS. Furthermore, patients carrying the AC and AA genotypes of rs7975232 showed a higher incidence of hypocitraturia compared to those with other genotypes (p < 0.05). The AA and GG genotypes of rs1042636 and the AA genotype of rs7652589 were significantly associated with hypercalciuria (p < 0.05). CCKS in this study population may be closely related to hypocitraturia caused by the VDR locus rs7975232 polymorphism and hypercalciuria caused by the CaSR locus rs1042636 and rs7652589 polymorphism.

Characterization of the zebrafish gabra1sa43718/sa43718 germline loss of function allele confirms a function for Gabra1 in motility and nervous system development

Mutation of the GABRA1 gene is associated with neurodevelopmental defects and epilepsy. GABRA1 encodes for the α1 subunit of the γ-aminobutyric acid type A receptor (GABAAR), which regulates the fast inhibitory impulses of the nervous system. Multiple model systems have been developed to understand the function of GABRA1, but these models have produced complex and, at times, incongruent data. Thus, additional model systems are required to validate and substantiate previous results. We sought to provide initial phenotypic analysis of a novel germline mutant allele. Our analysis provides a solid foundation for the future use of this allele to characterize gabra1 functionally and pharmacologically using zebrafish. We investigated the behavioral swim patterns associated with a nonsense mutation of the zebrafish gabra1 (sa43718 allele) gene. The sa43718 allele causes a decrease in gabra1 mRNA expression, which is associated with light induced hypermotility, one phenotype previously associated with seizure like behavior in zebrafish. Mutation of gabra1 was accompanied by decreased mRNA expression of gabra2, gabra3, and gabra5, indicating a reduction in the expression of additional α sub-units of the GABAAR. Although multiple sub-units were decreased, larvae continued to respond to pentylenetetrazole (PTZ), indicating that a residual GABAAR exists in the sa43718 allele. Proteomics analysis demonstrated that mutation of gabra1 is associated with abnormal expression of proteins that regulate synaptic vesicle fusion, vesicle transport, synapse development, and mitochondrial protein complexes. These data support previous studies performed in a zebrafish nonsense allele created by CRISPR/Cas9 and validate that loss of function mutations in the gabra1 gene result in seizure-like phenotypes with abnormal development of the GABA synapse. Our results add to the existing body of knowledge as to the function of GABRA1 during development and validate that zebrafish can be used to provide complete functional characterization of the gene.

1486-P: Role of HLA Class I Gene Alleles and Haplotypes in Type 1 Diabetes in Kuwaiti Children

1486-P: Role of HLA Class I Gene Alleles and Haplotypes in Type 1 Diabetes in Kuwaiti Children

Genetic Analysis of the Plasmid-Based Temperature-Lethal Mutant pa1792|lpxH(Ts) in Pseudomonas aeruginosa.

Many enzymes in the Raetz pathway for lipid A biosynthesis in Escherichia coli are essential. A homologous protein Pa1792|LpxH in Pseudomonas aeruginosa is known to complement the loss of LpxH in E. coli. Genome-wide transposon-insertion sequencing analysis indicates that lpxH is essential in P. aeruginosa. However, genetic analysis of lpxH in P. aeruginosa has not been carried out, partly because the conditional alleles of essential genes are not readily constructed. In this study, we first constructed a plasmid-based temperature-sensitive mutant ΔlpxH/pTS-lpxH or lpxH(Ts) in P. aeruginosa PAO1. Spot-plating assay indicated that lpxH(Ts) was lethal at a restrictive temperature, confirming its essentiality for growth. Microscopic analysis revealed that lpxH(Ts) exhibited an oval-shaped morphology, suggesting that lpxH was required for rod-shape formation. SDS-PAGE and Western blotting analysis showed that lpxH(Ts) failed to synthesize lipid A, consistent with its function in lipid A biosynthesis. Strong expression of lpxH but not the non-homologous isoenzyme lpxI or lpxG impeded growth and caused cell lysis, implying that lpxH-specific cofactors were required for this toxic effect in P. aeruginosa. Together, our results demonstrate that lpxH is essential for lipid A biosynthesis, rod-shaped growth, and viability in P. aeruginosa. We propose that this plasmid-based conditional allele is a useful tool for the genetic study of essential genes in P. aeruginosa.

The Importance of the FUT2 rs602662 Polymorphism in the Risk of Cardiovascular Complications in Patients after Kidney Transplantation.

The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes of vitamin B12 absorption and its transport between cells. FUT2 gene polymorphisms are associated with vitamin B12 levels in the body. Vitamin B12 deficiency associated with hyperhomocysteinemia is a major risk factor for cardiovascular diseases (CVDs), which are one of the main causes of death in patients after kidney transplantation. The aim of our study was to determine the impact of the rs602662 (G>A) polymorphism of the FUT2 gene on the functionality of transplanted kidneys and the risk of CVD in patients after kidney transplantation. The study included 402 patients treated with immunosuppression (183 patients taking cyclosporine (CsA) and 219 patients taking tacrolimus (TAC)). The analysis of the FUT2 rs602662 (G>A) polymorphism was performed using real-time PCR. Patients with CsA were more likely to be underweight (1.64% vs. 0.91%) and obese (27.87% vs. 15.98%), while those taking TAC were more likely to be of normal weight (39.27%) or overweight (43.84%). No statistically significant differences were observed comparing the mean blood pressure, both systolic and diastolic. The renal profile showed a higher median urea nitrogen concentration in patients with CsA (26.45 mg/dL (20.60-35.40) vs. 22.95 mg/dL (17.60-33.30), p = 0.004). The observed frequency of rs602662 alleles of the FUT2 gene was similar in the analyzed groups. The A allele was present in 43.7% of patients with CsA and 41.1% of those taking TAC (OR = 0.898; 95% CI: 0.678-1.189; p = 0.453). In the group with CsA, the GG genotype was present in 32.2% of patients, the GA in 48.1% and the AA in 19.7%. A similar distribution was obtained in the TAC group: GG-33.8%, GA-50.2%, and AA-16.0%. An association of genotypes containing the G allele with a higher incidence of hypertension was observed. The G allele was present in 65% of people with hypertension and in 56% of patients with normal blood pressure (p = 0.036). Moreover, the evaluation of the renal parameters showed no effect of the FUT2 polymorphism on the risk of organ rejection because the levels of creatinine, eGFR, potassium, and urea nitrogen were prognostic of successful transplantation. Our results suggest that the rs6022662 FUT2 polymorphism may influence the risk of cardiovascular diseases.

The potential of genome editing to create novel alleles of resistance genes in rice.

Rice, a staple food for a significant portion of the global population, faces persistent threats from various pathogens and pests, necessitating the development of resilient crop varieties. Deployment of resistance genes in rice is the best practice to manage diseases and reduce environmental damage by reducing the application of agro-chemicals. Genome editing technologies, such as CRISPR-Cas, have revolutionized the field of molecular biology, offering precise and efficient tools for targeted modifications within the rice genome. This study delves into the application of these tools to engineer novel alleles of resistance genes in rice, aiming to enhance the plant's innate ability to combat evolving threats. By harnessing the power of genome editing, researchers can introduce tailored genetic modifications that bolster the plant's defense mechanisms without compromising its essential characteristics. In this study, we synthesize recent advancements in genome editing methodologies applicable to rice and discuss the ethical considerations and regulatory frameworks surrounding the creation of genetically modified crops. Additionally, it explores potential challenges and future prospects for deploying edited rice varieties in agricultural landscapes. In summary, this study highlights the promise of genome editing in reshaping the genetic landscape of rice to confront emerging challenges, contributing to global food security and sustainable agriculture practices.

Full-resolution HLA and KIR gene annotations for human genome assemblies.

The human leukocyte antigen (HLA) genes and the killer cell immunoglobulin-like receptor (KIR) genes are critical to immune responses and are associated with many immune-related diseases. Located in highly polymorphic regions, it is difficult to study them with traditional short-read alignment-based methods. Although modern long-read assemblers can often assemble these genes, using existing tools to annotate HLA and KIR genes in these assemblies remains a nontrivial task. Here, we describe Immuannot, a new computation tool to annotate the gene structures of HLA and KIR genes and to type the allele of each gene. Applying Immuannot to 56 regional and 212 whole-genome assemblies from previous studies, we annotate 9931 HLA and KIR genes and found that almost half of these genes, 4068, have novel sequences compared with the current Immuno Polymorphism Database (IPD). These novel gene sequences are represented by 2664 distinct alleles, some of which contained nonsynonymous variations, resulting in 92 novel protein sequences. We demonstrate the complex haplotype structures at the two loci and report the linkage between HLA/KIR haplotypes and gene alleles. We anticipate that Immuannot will speed up the discovery of new HLA/KIR alleles and enable the association of HLA/KIR haplotype structures with clinical outcomes in the future.