Genetic Background Research Articles

Molecular monitoring of short- and long-term transcriptional effects of hair growth stimulating agents

Male-pattern hair loss (MPHL) is the most common form of hair loss in humans. Limited treatment options exist, which are not curative and vary in efficacy and invasiveness. Therapeutic and cosmetic hair growth stimulating agents that alleviate hair loss at a low risk of side effects are therefore of interest. The efficacy of hair growth-stimulating agents is mainly evaluated by hair comb tests and trichograms. These methods do not offer molecular insights, which can provide early insights into treatment response and may be useful in monitoring long-term compliance and efficacy. We propose a general concept for the molecular monitoring of hair growth stimulating agent treatment response in vivo, based on RNA and microRNA expression profiling before and during treatment. The molecular profile can be extended by individual genotype information to assess the impact of genetic constitution on treatment response. To test this methodological approach, 91 male participants with visible signs of and/or a family history of MPHL were assigned to four groups to investigate the effects of three hair growth stimulating agents versus placebo. mRNA- and microRNA-Seq was performed on plucked hair follicle samples before, after four days, and after six weeks of treatment. Genotyping was performed on DNA extracted from blood or saliva samples. Differential expression analyses identified 52 differentially expressed genes and 17 modulated pathways following treatment with the three hair growth stimulating agents. While the majority of effects were detectable after 6-week treatment, 23% of genes showed significant regulation after 4-day treatment. Integration with genetic data through pathway-based polygenic risk score analyses identified 5 associations between genetic background and treatment effects, pointing to a potential value of companion diagnostics for hair growth stimulating agents. Our data show that this molecular monitoring approach provides insights into hair growth stimulating agent treatment response as early as days within commencing treatment, and is suitable to monitor long-term treatment effects and compliance. Combined with genetic profiling, this approach may enable personalized prediction of treatment efficacy and compliance.

Haplotype analysis incorporating ancestral origins identified novel genetic loci associated with chicken body weight using an advanced intercross line

BackgroundThe genome-wide association study (GWAS) is a powerful method for mapping quantitative trait loci (QTL). However, standard GWAS can detect only QTL that segregate in the mapping population. Crossing populations with different characteristics increases genetic variability but F2 or back-crosses lack mapping resolution due to the limited number of recombination events. This drawback can be overcome with advanced intercross line (AIL) populations, which increase the number recombination events and provide a more accurate mapping resolution. Recent studies in humans have revealed ancestry-dependent genetic architecture and shown the effectiveness of admixture mapping in admixed populations.ResultsThrough the incorporation of line-of-origin effects and GWAS on an F9 AIL population, we identified genes that affect body weight at eight weeks of age (BW8) in chickens. The proposed ancestral-haplotype-based GWAS (testing only the origin regardless of the alleles) revealed three new QTLs on GGA12, GGA15, and GGA20. By using the concepts of ancestral homozygotes (individuals that carry two haplotypes of the same origin) and ancestral heterozygotes (carrying one haplotype of each origin), we identified 632 loci that exhibited high-parent (the heterozygote is better than both parents) and mid-parent (the heterozygote is better than the median of the parents) dominance across 12 chromosomes. Out of the 199 genes associated with BW8, EYA1, PDE1C, and MYC were identified as the best candidate genes for further validation.ConclusionsIn addition to the candidate genes reported in this study, our research demonstrates the effectiveness of incorporating ancestral information in population genetic analyses, which can be broadly applicable for genetic mapping in populations generated by ancestors with distinct phenotypes and genetic backgrounds. Our methods can benefit both geneticists and biologists interested in the genetic determinism of complex traits.

Phenotypic and Genetic Diversity Analysis of 18 Ornamental Strawberries

The red-flowered strawberry is a novel ornamental plant. This study aimed to assess the genetic diversity among ornamental strawberry germplasm resources. In this investigation, 17 red-flowered strawberry germplasms and 1 white-flowered strawberry germplasm were analyzed for genetic diversity and genetic relationships using a combination of phenotypic data, inter-simple sequence repeats (ISSR), and conserved DNA-derived polymorphism (CDDP) molecular markers. The results indicated that the 18 strawberry germplasms exhibited significant variability and genetic diversity at both phenotypic and molecular levels. The clustering results revealed notable differences between phenotypic clustering and molecular marker clustering, while the ISSR and CDDP markers grouped into broadly similar clusters. We further consolidated the ISSR and CDDP marker data to conduct the cluster analysis and population structure analysis of the 18 strawberry germplasms. The cluster analysis classified these germplasms into four clusters at a genetic similarity coefficient of 0.77. The population structure analysis categorized the germplasms into three groups, with 88.89% exhibiting a Q value ≥ 0.6, and 11.11% demonstrating a Q value < 0.6. This finding suggests that the genetic background of the 18 strawberry germplasms is relatively homogeneous. Notably, ‘Summer Breeze-Rose’ and ‘Summer Breeze-Cherry’ possess relatively complex genetic backgrounds (Q < 0.6). Furthermore, the floral, foliar, and plant traits of both germplasms display significant ornamental value and can serve as vital resources for the development and utilization of ornamental strawberries, as well as for the selection and breeding of new varieties.

Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring Citrobacter freundii in China with an IncR plasmid.

The rise of carbapenem-resistant Enterobacteriaceae coharboring KPC-2 and NDM-1 poses a significant public health threat. KPC-2-NDM-1-Citrobacter freundii is rarely reported in clinical settings. In this study, we report the largest cohort of eight KPC-2-NDM-1-C. freundii isolated from children with urinary tract infections. Comprehensive characterization, including antimicrobial susceptibility testing, plasmid conjugation, whole-genome sequencing, and comparative genomics, was conducted for these clinical strains. Antimicrobial susceptibility testing indicated that all strains were resistant to meropenem [minimal inhibitory concentration (MICs) ≥ 8 µg/mL] and imipenem (MICs > 8 µg/mL). Genotyping and comparative genomics analyses identified the eight KPC-2-NDM-1- C. freundii belonging to ST523, exhibiting a close relationship characterized by 45 single nucleotide polymorphisms. Whole-genome sequencing and plasmid analysis confirmed the presence of blaKPC-2 and blaNDM-1 on an IncR plasmid named pC275-2 with 46,050 bp. The blaNDM-1 was integrated within the blaNDM-1 related region, which includes ΔISAba125, blaNDM-1, ble-MBL, trpF, dsbD, and ISCR1, while the blaKPC-2 gene was located on a novel non-Tn4401 genetic element. The blaKPC-2 genetic architectures containing blaKPC-2 differed from classical structures, underscoring the ongoing evolution of these genetic elements.IMPORTANCEOur study described the largest cohort to date of eight ST523 KPC-2-NDM-1-C. freundii isolated from children with urinary tract infections. The cooccurrence of KPC-2, a serine β-lactamases, and NDM-1, a metallo-β-lactamase on an IncR plasmid pC275-2 from a clinical carbapenem-resistant C. freundii. The conserved insertion structure mediated the blaNDM-1, and the propagation of blaKPC-2 gene with a new genetic background using IncR plasmid in clinical settings promotes the emergence of superbugs necessitating vigilant monitoring. Our research detected that ST523 KPC-2- NDM-1-C. freundii were disseminated in a children's hospital. The potential spread of an IncR plasmid within the hospital raises concerns about the pandemic potential of this clone that produces two carbapenemases: KPC-2 and NDM-1. Further investigations will be necessary to control and prevent the spread of KPC-2-NDM-1-C. freundiis.

Decoding multiple sclerosis: Unravelling the complexities of pathogenesis, progression, mechanisms and therapeutic innovations.

Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disorder of the central nervous system (CNS) targeting myelinated axons. Pathogenesis of MS entails an intricate genetic, environmental, and immunological interaction. Dysregulation of immune response i.e. autoreactive T & B-Cells and macrophage infiltration into the CNS leads to inflammation, demyelination, and neurodegeneration. Disease progression of MS varies among individuals transitioning from one form of relapsing-remitting to secondary progressive MS. Research advances have unfolded various molecular targets involved in MS from oxidative stress to blood-brain barrier (BBB) disruption. Different pathways are being targeted so far such as inflammatory and cytokine signaling pathways to overcome disease progression. Therapeutic innovations have significantly transformed the management of MS, especially the use of disease-modifying therapies (DMTs) to reduce relapse rates and control disease progression. Advancements in research, neuroprotective strategies, and remyelination strategies hold promising results in reversing CNS damage. Various mice models are being adopted for testing new entities in MS research.

A deficiency screen identifies genomic regions critical for sperm head-tail connection.

The Sperm Neck provides a stable connection between the sperm head and tail, which is critical for fertility in species with flagellated sperm. Within the Sperm Neck, the Head-Tail Coupling Apparatus serves as the critical link between the nucleus (head) and the axoneme (tail) via the centriole. To identify regions of the Drosophila melanogaster genome that contain genetic elements that influence Head-Tail Coupling Apparatus formation, we undertook a 2 part screen using the Drosophila Deficiency kit. For this screen, we utilized a sensitized genetic background that overexpresses the pericentriolar material regulatory protein Pericentrin-Like Protein. We had previously shown that Pericentrin-Like Protein overexpression disrupts the head-tail connection in some spermatids, but not to a degree sufficient to reduce fertility. In the first step of the screen, we tested for deficiencies that in combination with Pericentrin-Like Protein overexpression causes a reduction in fertility. We ultimately identified 11 regions of the genome that resulted in an enhanced fertility defect when combined with Pericentrin-Like Protein overexpression. In the second step of the screen, we tested these deficiencies for their ability to enhance the head-tail connection defect caused by Pericentrin-Like Protein overexpression, finding 6 genomic regions. We then tested smaller deficiencies to narrow the region of the genome that contained these enhancers and examined the expression patterns of the genes within these deficiencies using publicly available datasets of Drosophila tissue RNAseq and Drosophila testes snRNAseq. In total, our analysis suggests that some deficiencies may contain single genes that influence Head-Tail Coupling Apparatus formation or fertility, while other deficiencies appear to be genomic regions rich in testis-expressed genes that might affect the Head-Tail Coupling Apparatus through complex, multigene interactions.

Updated genetic background of generalized pustular psoriasis as an autoinflammatory keratinization disease.

Generalized pustular psoriasis (GPP) is a severe autoinflammatory keratinization disease (AiKD) characterized by acute flares of widespread sterile pustules and high fever. GPP is potentially life-threatening. Recently clarified genetic predisposing factors for GPP suggest that the excessive activation of innate immune pathways in the skin, including of interleukin (IL)-1 and IL-36 signaling, plays a significant role in the GPP pathogenesis. IL36RN, CARD14, AP1S3, MPO, SERPINA3, BTN3A3, and MEFV have been identified as GPP-related genes. The pathogenesis of GPP provoked by variants in these seven genes is tightly associated with the excessive activation of innate immune pathways and the resulting autoinflammation in the skin. Various biologics, including inhibitors for the tumor necrosis factor, IL-17, and IL-23 pathways, are used as treatments for GPP. The new understanding of the genetic background of GPP, mentioned above, indicates that the genetic predisposing factors are predominantly related to the excessive activation of innate immunity and autoinflammation. In this context, inhibitors of inflammatory signaling, including of the IL-1 and IL-36 pathways, have been used in clinical practice and investigated as potential future therapies.

Analysis of immune cell activation in patients with diabetes foot ulcer from the perspective of single cell

BackgroundDiabetes mellitus (DM) can cause severe complications, including diabetic foot ulcers (DFU). There is a significant gap in understanding the single-cell ecological atlas of DM and DFU tissues.MethodsSingle-cell RNA sequencing data were used to create a detailed single-cell ecological landscape of DM and DFU. Enrichment analysis identified pathways involved in cellular subpopulations, and pseudo-time analysis inferred cell development processes. A gene regulatory network explored the role of transcription factors in DFU progression, and a potential herbal drug-target gene interaction network was constructed.ResultsIn the DFU group, immune cells were activated, with notable changes in several subpopulations. ATP5E was significantly overexpressed in Naive T cells, fibroblasts, endothelial cells, and CD8+ T cells in DM patients. Specific immune cell subsets, such as Naive T_RGCC, CTL_TYROBP_CL4, Mac_SLC40A1, and M1_CCL3L1, likely contribute to DFU formation through overactivation and proliferation, leading to tissue damage and ulcer exacerbation. Key genes TPP1, TLR4, and RIPK2 were identified, and 88 active ingredients in the herbal drug-target network showed strong correlations with these targets. Herbs like Angelica dahurica, Angelica sinensis, Boswellia carterii, liquorice, myrrh, and Semen armeniacae amarae were included.ConclusionsThis study offers insights into DM and DFU cytology. T cells in DFU are activated, attacking normal tissues and worsening tissue damage. The ATP5E gene may be related to the ecological remodeling of DM, and TPP1, TLR4, and RIPK2 are potential targets for DFU treatment.

QTL analysis in the Mianmai 902×Taichang 29 RIL population reveals the genetic basis for the high-yield of wheat cultivars Mianmai 902 in terms of spike and plant architecture

Spike-related traits and plant height (PH) are greatly associated with wheat yield. Identification of stable quantitative trait loci (QTL) for these traits is crucial for understanding the genetic basis for yield and their further application in breeding. In this study, QTL analysis for spikelet number per spike (SNS), spike length (SL), spike compactness (SC) and PH was performed using a recombinant inbred line (RIL) population derived from a cross between wheat cultivars Mianmai902 (MM902) and Taichang29 (TC29). Thirteen stably expressed QTLs were identified, and the most favorable alleles were contributed by MM902. The mjaor QTL, QSNS-MT.cib-2D, QSL-MT.cib-2D, QSC-MT.cib-2D, QSC-MT.cib-6 A, QPH-MT.cib-4B and QPH-MT.cib-4D, were repeatedly detected in multiple environments and explained 5.77-47.11% of the phenotypic variations. By employing the Kompetitive Allele Specific PCR markers, the most major QTLs were successfully validated in multiple populations derived from different genetic backgrounds. Moreover, the individual and pyramiding effects of major QTLs on SNS, SL, SC, PH, grain number per spike (GNS) and thousand-grain weight (TGW) were investigated and their potential utilization value in breeding was showcased. Ppd-D1 was predicted as the candidate for QSNS/SL/SC/PH-MT.cib-2D, and MM902 carried the Ppd-D1d allele. Ppd-D1d is rare in Chinese winter wheat cultivars and may be an elite alternative allele of the Ppd-D1a allele. In summary, these QTLs revealed the genetic basis of the spike-related traits and PH of MM902, which partially contributed to the high yield of MM902 and have application potential in wheat breeding by optimizing spike morphology and PH to improve yield.

The metabolic hypothesis for restrictive eating behaviors: A computational and evolutionary approach.

Restrictive eating behaviors, widespread in humans and animals, are often conceptualized as maladaptive, but may serve adaptive purposes under specific circumstances. To investigate the adaptive potential of restrictive eating behaviors. Computational models explored the relationship between food availability, basal metabolic rate, and restrictive eating behaviors. The evolutionary conservation of genes associated with both basal metabolic rate and restrictive eating behaviors was evaluated. The propensity to engage in restrictive eating behaviors protected against negative energy balances at times of food volatility, implying ecological fitness potential. A high degree of conservation across species was observed in retrieved genes, implying selective evolutionary constraints. Restrictive eating behaviors may represent a maladaptive outcome of evolutionary constraints on protective metabolic mechanisms. The higher prevalence of restrictive eating in women could stem from a greater reliance on protective strategies, highlighting the need for further exploration of sex-specific genetic and environmental interactions.

The Identification of Methylation Profiles of FTO and PPARG Genes in Type 2 Diabetes Mellitus Patients

Type 2 diabetes (T2DM) is a complex, metabolic disease driven by genetic susceptibilities, environmental interactions, and various genes. Nowadays, increasing number of studies show the relationship between diabetes mellitus (DM) and epigenetics, especially DNA methylation. In this study, we aimed to measure the methylation levels of fat mass and obesity associated (FTO) and peroxisome proliferator activated receptor gamma (PPARG) in the peripheral blood samples of patients with clinical diagnosis of T2DM. In our study, whole blood was taken from T2DM patients (n=43) who applied to the Endocrinology Outpatient Clinic and from age-gender-matched healthy individuals (n=42). After the bisulfide conversion of isolated genomic DNAs from whole blood samples, the methylation profiles of target genes were analyzed with methyl-specific PCR and gel electrophoresis methods. Post-statistical analyses, no significant difference was found between the T2DM and control groups regarding FTO methylation status. The methylation level of PPARG gene in T2DM was significantly higher compared to the control group. Given the insulin sensitizing effects of PPARG, our findings confirm the possibility that methylation-mediated suppression of PPARG gene expression may lead to elevation of insulin resistance in T2DM patients. Further gene expression studies with more patients and quantitative methods will be required to better understand the effects of methylation in the PPARG gene in T2DM patients and its relationship to the disease.

A chromosome-scale reference genome of the Banna miniature inbred pig

The Banna miniature inbred pig (BN) is an intensively inbred line for biomedical research and xenotransplantation due to its low individual variation and stable genetic background. Although it is originated from the Diannan miniature pig (DN), substantial genetic changes have actually occurred. However, the lack of a BN reference genome has limited studies on the complete genomic architecture and utilization as a biomedical model. Here, we present a high-quality genome for BN using PacBio HiFi and Hi-C sequencing technologies, with a total length of 2.66 Gb, a scaffold N50 of 143.60 Mb, and 97.59% of the sequences anchored to chromosomes. Its BUSCO score is 96.30%, higher than porcine reference assembly and DN. The genome contains 48.49% of repeats, 19,756 protein-coding genes, and 7,207 non-coding RNAs according to our annotation. The OMArk score shows a proteome completeness and consistency of 99.58% and 93.62%, respectively. These findings indicate that the chromosome-scale genome of BN provides a valuable resource for studying the genetic basis of inbreeding, facilitating further research and clinical applications.

Genome-Wide Structural Variation Analysis and Breed Comparison of Local Domestic Ducks in Shandong Province, China

Structural variations in the duck genome significantly impact the environmental adaptability and phenotypic diversity of duck populations. Characterizing these SVs in local domestic duck breeds from Shandong province offers valuable insights for breed selection and the development of new breeds. This study aimed to profile the genomic SVs in three local duck breeds (Matahu duck, Weishan partridge duck, and Wendeng black duck) and explore their differential distributions. A total of 21,673 SVs were detected using LUMPY (v0.2.13) and DELLY (v1.0.3) software, with 46% located in intergenic regions, 33% in intronic regions, and frameshift deletions being the most prevalent in exonic regions (3%). SVs distribution showed a decreasing trend with shorter chromosome lengths. Population structure analysis revealed distinct genetic profiles, with Matahu and Weishan partridge ducks showing closer affinities and the Wendeng black duck having a more homogeneous genetic background, likely due to geographic isolation. Functional annotation identified genes related to nervous system development, mitosis, spindle assembly, and energy metabolism. Notable genes included PLXNA4, NRP2, SEMA3A, PTEN, MYBL2, ADK, and COX4I1. Additionally, genes such as PRKG1, GABRA2, and FSHR were linked to energy metabolism and reproductive activity. The study provides a comprehensive analysis of SVs, revealing significant genetic differentiation and identifying genes associated with economically important traits, offering valuable resources for the genetic improvement and breeding of local duck breeds.

Screening of the key genes and signaling pathways for schizophrenia using bioinformatics and next generation sequencing data analysis

Schizophrenia is thought to be the most prevalent chronic psychiatric disorder. Researchers have identified numerous proteins associated with the occurrence and development of schizophrenia. This study aimed to identify potential core genes and pathways involved in schizophrenia through exhaustive bioinformatics and next generation sequencing (NGS) data analyses using GSE106589 NGS data of neural progenitor cells and neurons obtained from healthy controls and patients with schizophrenia. The NGS data were downloaded from the Gene Expression Omnibus database. NGS data was processed by the DESeq2 package in R software, and the differentially expressed genes (DEGs) were identified. Gene ontology (GO) enrichment analysis and REACTOME pathway enrichment analysis were carried out to identify potential biological functions and pathways of the DEGs. Protein-protein interaction network, module, micro-RNA (miRNA)-hub gene regulatory network, transcription factor (TF)-hub gene regulatory network, and drug-hub gene interaction network analysis were performed to identify the hub genes, miRNA, TFs, and drug molecules. Potential hub genes were analyzed using receiver operating characteristic curves in the R package. In this investigation, an overall 955 DEGs were identified: 478 genes were remarkably upregulated and 477 genes were distinctly downregulated. These genes were enriched for GO terms and pathways mainly involved in the multicellular organismal process, G protein-coupled receptor ligand binding, regulation of cellular processes, and amine ligand-binding receptors. MYC, FN1, CDKN2A, EEF1G, CAV1, ONECUT1, SYK, MAPK13, TFAP2A, and BTK were considered the potential hub genes. The MiRNA-hub gene regulatory network, TF-hub gene regulatory network, and drug-hub gene interaction network were constructed successfully and predicted key miRNAs, TFs, and drug molecules for schizophrenia diagnosis and treatment. On the whole, the findings of this investigation enhance our understanding of the potential molecular mechanisms of schizophrenia and provide potential targets for further investigation.

Loss of STAT3 in osteoblasts has detrimental and sexually dimorphic effects on skeletal development.

Studies with genetically modified mice have implicated the transcriptional regulator STAT3 as a key modulator of bone development. STAT3-OKO knockout mouse lines were generated in two genetic backgrounds, pure C57BL/6 (STAT3-OKO-BL) and mixed C57BL/6, CD1 (STAT3-OKO-M). Both lines exhibited defective postnatal bone development resulting in reduced body weight and shortened femurs that displayed low bone mineral density as well as cortical widening and thinning in the diaphyseal region. Remarkably, each of these defects displayed sexual dimorphism that was dependent on genetic background: the phenotype was entirely male-specific in STAT3-OKO-M but not in STAT3-OKO-BL, in which defects were similar in both sexes. However, both lines exhibited a male-specific bone defect in mineralization, and also in bone mechanical properties related to bone quality, such as yield stress and ultimate stress. On the other hand, bone mechanical properties such as ultimate force, that may reflect density and macrostructure rather than bone quality, showed male-specific defects only in STAT3-OKO-M. These findings suggest that STAT3 may regulate multiple sex-dependent mechanisms in bone development that control either mineralization or bone accrual, and that the sex-dependence of at least some of these mechanisms is affected by genetic background. Finally, we used CRISPR/Cas9 to generate STAT3-deficient preosteoblastic cells from immortalized wild-type bone marrow stem cells and showed that the defective osteoblastic differentiation of STAT3-ablated cells was associated with reduced gene expression of Wnt3a and Wnt5a, consistent with other studies that identify Wnt signaling pathways as potential effector mechanisms for STAT3-mediated regulation of bone development.

The influence of fetal sex on antenatal maternal glucose and insulin dynamics

The ‘Developmental Origins of Health and Disease’ (DOHaD) hypothesis postulates that exposures during critical periods of development and growth, including maternal hyperglycemia, can have significant consequences for short- and long-term health in offspring. The influence of fetal status on maternal (patho)physiology is less well understood but gaining attention. Fetal sex specifically may be an independent risk factor for a range of adverse pregnancy outcomes, including increased gestational diabetes mellitus (GDM) frequency with male fetuses in multi-ethnic populations. Fetal sex has been thought to modulate maternal glucose metabolism, including insulin dynamics, through complex genetic and hormonal interactions. Mechanisms have not been fully elucidated, however, but may relate to sexual dimorphism in maternal-fetal-placental interactions. We review current evidence on the potential influence of fetal sex on maternal glucose and insulin dynamics, and fetal outcomes.

Associations Between Clinical Manifestations of SARS-CoV-2 Infection and HLA Alleles in a Caucasian Population: A Molecular HLA Typing Study

Background and Objectives: Severe COVID-19 still constitutes an important health problem. Taking into account the crucial role of HLA in immune reactions, evaluation of the impact of HLA on COVID-19 risk and clinical course seemed necessary, as the already available data are inconsistent. The aim of the present study was to compare the HLA profiles of patients with symptomatic SARS-CoV-2 infection and a healthy control group, as well as to compare HLA allele frequencies in patients with severe and non-severe courses of COVID-19. Materials and Methods: HLA classes were genotyped using a next-generation sequencing method in 2322 persons, including 2217 healthy hematopoietic stem cell potential donors and 105 patients with symptomatic COVID-19. Results: Symptomatic course of SARS-CoV-2 infection appeared to be associated with the presence of HLA-A*30:01, B*44:02, B*52:01, C*05:01, C*17:01, and DRB1*11:02, while HLA-C*07:04 and DQB1*03:03 seem to play a protective role. Moreover, we demonstrated that the severe symptomatic course of COVID-19 can be associated with the presence of HLA-B*08:01, C*04:01, DRB1*03:01, and DQB1*03:01, while HLA-DRB1*08:01 appeared to be protective against severe COVID-19 disease. Conclusions: Identification of alleles that are potentially associated with symptomatic SARS-CoV-2 infection as well as the severe course of COVID-19 broadens the knowledge on the genetic background of COVID-19 course and can constitute an important step in the development of personalized medicine.

The Influence of Genetic Polymorphisms in Cytochrome P450 (CYP1A1 and 2D6) Gene on the Susceptibility to Philadelphia Negative Chronic Myeloid Leukemia in Sudanese Patients

The most frequent type of leukemia in Africa is chronic myeloid leukemia (CML). The genetic background of the rarer Philadelphia chromosome (Ph) Ph-ve (BCR-ABL-ve) subform of CML is largely unknown in African patients. Therefore, in this study, we aimed to investigate the role of CYP1A1 and 2D6 SNPs in the pathogenesis of Ph-ve CML in the Sudanese population. A total of 126 patients were selected for analysis. DNA was isolated from Ph-ve CML patients and a control group for PCR-RFLP analysis of SNPs CYP1A1*2C and CYP2D6*4. The CYP1A1 gene significantly expressed the GG variant genotype (p < 0.05) in 23.1% of the Ph-ve CML patients and 8% of the control group. In contrast, the CYP2D6 GA genotype was strongly associated with a reduced risk of developing Ph-ve CML (p < 0.005) with a frequency of 50% in Ph-ve patients and 93% in the control group. CYP1A1 GG polymorphism was prevalent among patients with Ph-ve CML, suggesting its role in disease development. CYP2D6 GA (IM) polymorphism was uncommon among patients, compared with the control group, possibly indicating a protective role of the polymorphisms from Ph-ve CML. This study demonstrates an association between key metabolic SNPs and Ph-ve CML and highlights the role that altered xenobiotic metabolism may play in the development of several human leukemias.

Acute Form of Sarcoidosis (Löfgren Syndrome): A Case Report

Sarcoidosis is a disorder that affects multiple systems with unclear causes and is relatively rare. The defining characteristic of this disease is the presence of granulomas in various organs in the human body. The incidence and presentation are changeable according to many factors, such as geography, ethnicity, sex, and genetic background. It is highest in Scandinavians. Löfgren syndrome represents a sudden manifestation of sarcoidosis, constituting approximately 10% of all cases. The classical signs and symptoms include bilateral symmetric hilar lymphadenopathy, fever, multiple joint swelling, and skin lesions known as erythema nodosum. Diagnosis of the disease can be quite challenging owing to its infrequent occurrence and the limited availability of sensitive and specific diagnostic tools, tests, and changeable clinical pictures that may suggest different aetiologies. Early diagnosis of Löfgren syndrome will ensure rapid treatment and fewer complications. This review presents the case of a 27-year-old healthy female with sudden onset of bilateral knee joint pain, swelling, erythema nodosum, and fever. Laboratory tests revealed elevated inflammatory parameters. Chest CT and chest X-ray revealed mediastinal and hilar lymphadenopathy, suggesting Löfgren syndrome. This report emphasises the broad spectrum of mimicry observed in cases of acute sarcoidosis, with a focus on the clinical picture and standard differentials that must be carefully evaluated to exclude other inflammatory and malignant conditions. The patient achieved full remission following symptomatic treatment.

FLEXIBILITY IN GENE COEXPRESSION AT DEVELOPMENTAL AND EVOLUTIONARY TIMESCALES.

The explosion of next-generation sequencing technologies has allowed researchers to move from studying single genes, to thousands of genes, and thereby to also consider the relationships within gene networks. Like others, we are interested in understanding how developmental and evolutionary forces shape the expression of individual genes, as well as the interactions among genes. To this end, we characterized the effects of genetic background and developmental environment on brain gene coexpression in two parallel, independent evolutionary lineages of Trinidadian guppies ( Poecilia reticulata ). We asked whether connectivity patterns among genes differed based on genetic background and rearing environment, and whether a gene's connectivity predicted its propensity for expression divergence. In pursuing these questions, we confronted the central challenge that standard approaches fail to control the Type I error and/or have low power in the presence of high dimensionality (i.e., large number of genes) and small sample size, as in many gene expression studies. Using our data as a case study, we detail central challenges, discuss sample size guidelines, and provide rigorous statistical approaches for exploring coexpression differences with small sample sizes. Using these approaches, we find evidence that coexpression relationships differ based on both genetic background and rearing environment. We report greater expression divergence in less connected genes and suggest this pattern may arise and be reinforced by selection.