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In the recent years, there was an important improvement in the understanding of the pathogenesis of hereditary angioedema (HAE). Notwithstanding, in a large portion of patients with unknown mutation (HAE-UNK) the genetic cause remains to be identified. To identify new genetic targets associated with HAE, a large Argentine family with HAE-UNK spanning 3 generations was studied. Whole exome sequencing was performed on affected family members to identify potential genetic variants associated with HAE-UNK. In silico analyses and experimental studies were applied to assess the role of the identified gene variant. A missense variant (p.D239N) in DAB2IP was identified. The variant occurred in the C2-domain, the region interacting with vascular endothelial growth factor receptor 2 (VEGFR2). It was found to be rare, and predicted to have a detrimental effect on the functionality of DAB2IP. Protein structure modeling predicted changes in the mutant p.D239N protein structure, impacting protein stability. The p.D239N variant affected the subcellular localization of VEGFR2. Cells transfected with the DAB2IP-239N transcript exhibited an intracellular distribution, and VEGFR2 remained associated with the cell membrane. The altered localization pattern indicated reduced colocalization of the mutant protein with VEGFR2, suggesting a diminished ability of VEGFR2 binding. The study identified a novel missense variant (p.D239N) in DAB2IP in a family with HAE-UNK and highlighted the role of dysregulated VEGF-mediated signaling in altered endothelial permeability. DAB2IP loss-of-function pathogenic variants lead to the impairment of the endothelial VEGF/VEGFR2 ligand system and represent a new pathophysiologic cause of HAE-UNK. [ABSTRACT FROM AUTHOR]

The global human population is exponentially increasing, which requires the production of quality food through efficient reproduction as well as sustainable production of livestock. Lack of knowledge and technology for assessing semen quality and predicting bull fertility is hindering advances in animal science and food animal production and causing millions of dollars of economic losses annually. The intent of this systemic review is to summarize methods from computational biology for analysis of gene, metabolite, and protein networks to identify potential markers that can be applied to improve livestock reproduction, with a focus on bull fertility. We provide examples of available gene, metabolic, and protein networks and computational biology methods to show how the interactions between genes, proteins, and metabolites together drive the complex process of spermatogenesis and regulate fertility in animals. We demonstrate the use of the National Center for Biotechnology Information (NCBI) and Ensembl for finding gene sequences, and then use them to create and understand gene, protein and metabolite networks for sperm associated factors to elucidate global cellular processes in sperm. This study highlights the value of mapping complex biological pathways among livestock and potential for conducting studies on promoting livestock improvement for global food security. [ABSTRACT FROM AUTHOR]

• Cerebellar atrophy was not uncommon in genetic epileptic encephalopathies (EEs). • This cohort study revealed 15 % of genetic EE individuals had cerebellar atrophy. • A systematic review showed 32 genetic EEs associated with cerebellar atrophy. • Cerebellar atrophy could act as a molecular test precursor in genetic EEs. To analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs). This research included a retrospective cohort study conducted from January 2016 to December 2023 and a systematic review on cerebellar atrophy in genetic EEs. Pediatric individuals who were diagnosed with EEs based on electroclinical features, carried causative gene variants, and exhibited cerebellar atrophy were recruited. Electroclinical features, neuroimaging findings, and causative variants of eligible individuals were analyzed. The cohort study showed 10 of 67 pediatric individuals (10/67; 15 %) who were diagnosed with genetic EEs had cerebellar atrophy; and 6 of the 10 individuals (6/10; 60 %) exhibited cerebellar signs. Diagnostic delay between the detection of cerebellar atrophy and the identification of genetic diagnosis existed in 6 individuals (6/10; 60 %) and the median duration was 4.4 years. A total of 32 genes, including 31 genes from the literature review and a newly identified SCN2A gene in this cohort, were reported associated with cerebellar atrophy in genetic EEs. Twenty-six genes (26/32; 81 %) accounted for cerebellar atrophy associated with other brain anomalies and 6 genes (6/32; 19 %) caused isolated cerebellar atrophy. Twenty-five genes (25/32; 78 %) showed late-onset cerebellar atrophy identified after the age of 1 year old. Cerebellar atrophy is not uncommon in genetic EEs and may serve as an indicator for molecular diagnosis in clinical practice. To shorten the diagnostic delay, follow-up neuroimaging study is crucial because of high rate of clinico-radiological dissociation and late-onset cerebellar atrophy in this patient group. [ABSTRACT FROM AUTHOR]

The applications of centrality measures in protein-protein interaction (PPI) network analysis are diverse and encompass fundamental biological insights; cancer disease-related discoveries, and practical implications for drug development. This multidimensional approach in PPI network analysis provides a comprehensive understanding of the pivotal elements and their impact on biological systems. Analyzing centrality measures in PPI networks enables the identification of essential proteins, hub and bottleneck proteins that occupy strategic positions within the PPI network structure. Essential proteins in PPI networks are significant elements that indicate their importance in maintaining PPI network integrity and functionality. Studying centrality measures can reveal hidden patterns and relationships within these PPI networks. This paper identifes PPI networks with a high degree of connectivity ("hubs") and proteins with high betweenness centrality (bottlenecks), along with closeness centrality and clustering coefficient. This measure's significance in PPI networks has implications for various felds. The proposed approach successfully identifed and characterized infuential proteins and found the top 20 essential proteins. These proteins likely hold significant functional importance through hubs and bottlenecks and serve as potential targets for further investigation. This approach has the potential to identify essential proteins involved in cancer diseases. Leveraging centrality measures in the analysis of PPI networks ofers a multifaceted approach to understanding cancer biology and its implications for personalized medicine, drug design, and the development of innovative cancer therapies. [ABSTRACT FROM AUTHOR]

Background: Changes induced by monosodium glutamate (MSG) can negatively impact milk production and secretion, among other adverse effects. This study aimed to investigate the effects of MSG consumption on receptor gene expression and quantification of hormones and receptors, as well as oxidative stress biomarkers and other lactogenic parameters in lactating animals. Twenty-four female Wistar rats, nine weeks of age, were randomly assigned to four groups, each containing six rats, at parturition. The rats in groups II, III, and IV were given varying doses of monosodium glutamate (MSG); while, group I was given distilled water and served as the control. The experimental period lasted two (2) weeks. Results: The groups administered with MSG showed a significant decrease in mammary PRLR gene expression (p < 0.05), as well as a marked reduction (p < 0.05) in mammary PRLR, OXT receptor, AQP-3, brain antioxidant enzymes (SOD, GPx, and CAT), and pituitary SOD compared to the control group (p < 0.05). Furthermore, there was a significant increase (p < 0.05) in reactive oxygen species levels in the serum and mammary gland homogenates, erythrocyte osmotic fragility, and elevated (p < 0.05) brain and pituitary MDA levels in the MSG-administered groups compared to the control group. Daily milk yields were significantly decreased (p < 0.05) in the MSG-administered groups between days 10 and 14 of lactation. Conclusion: The findings of this study suggest that prolonged consumption of MSG could interfere with lactation-associated functions via increased ROS production, reduced antioxidants, decreased AQP-3, mammary prolactin and oxytocin receptors, and prolactin receptor mRNA in lactating Wistar rats. [ABSTRACT FROM AUTHOR]

Hypertensive disorders in pregnancy (HDP) are the leading cause of perinatal mortality worldwide. Inflammatory responses induced by insufficient placental perfusion have become a focal point in understanding the pathogenesis and aetiology of HDP and developing reliable and consistent biomarkers. Therefore, this study aims to identify gene signatures linked to the pathophysiology of HDP (gestational hypertension and early and late-onset pre-eclampsia). RNA was extracted from the maternal serum from the blood samples collected from different groups of HDP patients. A multiplex inflammation panel (255 inflammatory and housekeeping genes) and further gene expression analysis using NanoString Digital Direct Detection were done. The prominent expressions of these genes were further validated through qPCR techniques. NanoString analysis identified nine unique, significantly expressed genes (MAPK1, MAPK3, MAFF, HLA-DRA, IL12B, RHOA, MASP2, MEF2A and NR3C1) between specific group comparisons of different HPD classes and the normotensive groups. The qPCR showed that the HLA-DRA gene was significantly upregulated in the early-onset pre-eclamptic and gestational hypertensive group compared to its respective normotensive group. In contrast, MAFF and MEF2A were significantly downregulated in both HDPs compared to their controls. The MAPK1 gene was significantly higher in the early-onset group compared to the gestational hypertensive and normotensive groups. The upregulation of these distinctive genes in hypertensive groups compared to normotensives confirmed their diagnostic potential. Therefore, HLA-DRA, MAFF and MEF2A could be candidate markers of HDP, while the MAPK1 gene could be a differentiating marker between early-onset pre-eclampsia and gestational hypertension. • This study aimed to identify gene signatures linked to the pathophysiology of hypertensive disorders in pregnancy. • Nine unique, differentially expressed genes among different HPD classes were identified in this study. • HLA-DRA, MAFF and MEF2A genes were identified as possible biomarkers of HDP. • MAPK1 gene could be a differentiating marker between early-onset preeclampsia and gestational hypertension. [ABSTRACT FROM AUTHOR]

Multiple lifestyle-based childhood obesity interventions have been conducted to address childhood obesity, but individual's response to the universal intervention approach varied greatly. Whether gene variants related to children and adolescents' varied responses to obesity interventions remained unclear. To determine the associations of gene variants with the changes in obesity- and metabolism-related indicators after obesity interventions in children and adolescents. Ten databases and registers (including grey literature) were searched. The lifestyle-based obesity interventions in children and adolescents (≤18 years) that reported the changes in obesity- (body mass index (BMI), BMI Z-score, waist circumference (WC), waist-to-hip ratio (WHR), etc) and metabolism-related (glucose, cholesterol, etc) indicators by genotype after interventions were included. Our primary outcome was the mean difference of the changes in BMI Z-score by genotype after interventions, and secondary outcomes were changes in the remaining obesity- and metabolism-related indicators after interventions. We used the random-effects model to synthesize the results. This review included 50 studies (15,354 children and adolescents with overweight/obesity) covering 102 genes and 174 single nucleotide polymorphisms (SNPs). Approximately three-quarters of SNPs showed no evidence of association with the changes in obesity- or metabolic-related indicators after interventions. One quarter of SNPs were minorly associated with the changes in the BMI Z-score (median effect size: 0.001) with little clinical significance. Only 6 (12 %) studies focused on the accumulated effect of multiple gene variants. Gene variants that have been explored appear to play a minor role in lifestyle-based obesity interventions in children and adolescents. More high-quality studies based on the design of randomized controlled trials are needed to examine the accumulated effect of multiple gene variants in childhood obesity interventions. This systematic review and meta-analysis was registered at PROSPERO as CRD42022312177. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Despite their increased application, the heritability of Alzheimer's disease (AD)–related blood‐based biomarkers remains unexplored. METHODS: Plasma amyloid beta 40 (Aβ40), Aβ42, the Aβ42/40 ratio, total tau (t‐tau), and neurofilament light (NfL) data came from 1035 men 60 to 73 years of age (μ = 67.0, SD = 2.6). Twin models were used to calculate heritability and the genetic and environmental correlations between them. RESULTS: Additive genetics explained 44% to 52% of Aβ42, Aβ40, t‐tau, and NfL. The Aβ42/40 ratio was not heritable. Aβ40 and Aβ42 were genetically near identical (rg = 0.94). Both Aβ40 and Aβ42 were genetically correlated with NfL (rg = 0.35 to 0.38), but genetically unrelated to t‐tau. DISCUSSION: Except for Aβ42/40, plasma biomarkers are heritable. Aβ40 and Aβ42 share mostly the same genetic influences, whereas genetic influences on plasma t‐tau and NfL are largely unique in early old‐age men. The absence of genetic associations between the Aβs and t‐tau is not consistent with the amyloid cascade hypothesis. [ABSTRACT FROM AUTHOR]

To solve the breeding problem of the serious shortage of female cassava flowers, cassava variety 'Xinxianxuan 048' was used as the experimental material. Transcriptional sequencing technology was used to analyze the biological information of differentially expressed genes in female and male flowers during the critical period of cassava flower sex differentiation, explore the functions of differentially expressed genes and possible regulatory pathways involved, excavate candidate genes related to female differentiation, and verify the sequencing results by qRT-PCR method. The results showed that: There were 545 differentially expressed genes between male and female cassava flowers at the critical stage of gender differentiation. Among them, 48.63% of the differential genes were enriched in GO pathway of floral organ morphogenesis and development, and the genes enriched in plant phenylpropanol biosynthesis and plant hormone signal transduction were the most. AGL11, YABBY4, CRC, SUP, and other flower sex differentiation genes were significantly up-regulated in female flowers. Four genes of the cytokinin signaling pathway, including HK4, HPt4, ARR8, and ARR12, were significantly up-regulated in female flowers, while IAA14, GH3, SAUR22, and SAURR20, the early auxin response genes, were significantly down-regulated in female flowers. Therefore, the sexual differentiation of cassava flowers mainly involved the biological pathways of pollen, gametophyte, floral organ morphogenesis and development, and two metabolic pathways of plant phenylpropanoid biosynthesis and plant hormone signal transduction. Cytokinin and auxin might be the main hormones in cassava female flower differentiation. AGL11, YABBY4, CRC, SUP, HK4, HPt4, ARR8, and ARR12 may be positive regulators of cassava female flower differentiation. [ABSTRACT FROM AUTHOR]

Background Certain Bacillus species play a vital role in polyhydroxyalkanoate (PHA) production. However, most of these isolates did not properly identify to species level when scientifically had been reported. Results From NGS analysis, 5719 genes were predicted in the de novo genome assembly. Based on genome annotation using RAST server, 5,527,513 bp sequences were predicted with 5679 bp number of protein-coding sequence. Its genome sequence contains 35.1% and 156 GC content and contigs, respectively. In RAST server analysis, subsystem (43%) and non-subsystem coverage (57%) were generated. Ortho Venn comparative genome analysis indicated that Bacillus sp. BNPI-92 shared 2930 gene cluster (core gene) with B. cereus ATCC 14579T (AE016877), B. paranthracis Mn5T (MACE01000012), B. thuringiensis ATCC 10792T (ACNF01000156), and B. antrics Amen T (AE016879) strains. For our strain, the maximum gene cluster (190) was shared with B. cereus ATCC 14579T (AE016877). For Ortho Venn pair wise analysis, the maximum overlapping gene clusters thresholds have been detected between Bacillus s p.BNPI-92 and Ba. cereus ATCC 14579T (5414). Average nucleotide identity (ANI) such as OriginalANI and OrthoANI, in silicon digital DND-DNA hybridization (isDDH), Type (Strain) Genome Server (TYGS), and Genome-Genome Distance Calculator (GGDC) were more essentially related Bacillus sp. BNPI-92 with B. cereus ATCC 14579T strain. Therefore, based on the combination of RAST annotation, OrthoVenn server, ANI and isDDH result Bacillus sp.BNPI-92 strain was strongly confirmed to be a B. cereus type strain. It was designated as B. cereus BNPI-92 strain. In B. cereus BNPI-92 strain whole genome sequence, PHA biosynthesis encoding genes such as phaP, phaQ, phaR (PHA synthesis repressor phaR gene sequence), phaB/phbB, and phaC were predicted on the same operon. These gene clusters were designated as phaPQRBC. However, phaA was located on other operons. Conclusions This newly obtained isolate was found to be new a strain based on comparative genomic analysis and it was also observed as a potential candidate for PHA biosynthesis. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance is emerging as a global public threat. However, it remains poorly investigated in the context of periodontal therapy. The aim of the study was to investigate the complete diversity of antibiotic resistance genes in a German population. Methods: Thirty‐nine volunteers with periodontitis contributed to the present study with one to four periodontal pockets for a total of 124 subgingival samples. Samples were analyzed using shotgun metagenomics. Results: A total of 19 antibiotic resistance genes from six antibiotic classes were detected in subgingival biofilm. Two thirds of the volunteers (n = 26/39) showed antibiotic resistance genes for at least one of the antibiotic classes used for periodontal treatment in dental practice or research: beta‐lactam, lincosamide, macrolide, nitroimidazole, and tetracycline. Macrolide was the most abundant class detected (21/39 patients). Conclusions: Findings from our study suggest a high prevalence of antibiotic resistance genes in periodontal pockets from German volunteers. We recommend the development and broader use of molecular diagnostic tests for antibiotic resistance in dental practice to ensure treatment success and to minimize antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background: Evidence has shown that glucocorticoid-induced transcript 1 (GLCCI1) single nucleotide polymorphism (SNP) rs37937 is associated with asthma. Objectives: The objective of this study was to investigate whether the GLCCI1 SNP rs37937 is a risk factor for allergic rhinitis (AR) in a Chinese Han population. Methods: A total of 220 individuals including 109 AR patients and 111 healthy subjects were included. The genotyping of GLCCI1 rs37973 was performed by the SNaPshot method. The correlations of rs37973 polymorphism, AR risk, and clinical characteristics were further analyzed, as well as the treatment response to intranasal corticosteroids (INCS) in AR patients of different genotypes. Results: Three GLCCI1 rs37973 SNP genotypes were identified in both AR patients and healthy subjects. Significant association between rs37973 polymorphism and AR under allele model, dominant model, heterozygote model, and homozygote model were shown. The A allele frequency of SNP rs37973 in AR was significantly higher than that in controls. The serum total immunoglobulin E (IgE) in AR patients of AA genotype was significantly higher than in patients of GA and GG genotype, and the serum total IgE in GA genotype was significantly higher than in GG genotype. Interestingly, after 4 weeks of INCS treatment for AR patients, the improvement of the nasal itching score, sneezing score, runny nose score, total nasal symptom score, and visual analog scale score of the GG genotype were worse than the AA or GA genotype. Conclusion: The GLCCI1 rs37937 polymorphism is associated with the risk of developing AR and the response to INCS treatment in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) gene-specific methylation and recurrent spontaneous abortion (RSA). Methods: A total of 50 RSA patients who visited our hospital were recruited in the study group; 50 multiparous women who underwent physical examinations during the same period were enrolled in the control group. The levels of homocysteine, folic acid, and vitamin B12 and their MTHFR gene polymorphism and specific methylation were measured in both groups. The Logistic regression equation was used to analyze the correlation between MTHFR gene-specific methylation and RSA. Results: The methylated allele MM was not found in the control group, and the frequency in the study group was 1.19%. The frequency of the MU genotype in the study group 32.93% was higher than that in the control group 12.45%. The frequency of methylated alleles of CC and CT genotypes carrying MTHFR C677T polymorphism in the study group was higher than that in the control group (P < 0.05). There was no significant difference in the TT genotype between the two groups (P > 0.05). Multivariate Logistic regression analysis exhibited that patients with methylated alleles of CC genotype had a risk of RSA increased by 1.167 times, and the risk increased by 2.500 times in patients with methylated alleles of CT genotype (P < 0.05). 83.33% of RSA patients carrying methylated alleles affected hyperhomocysteinemia. In patients with elevated homocysteine levels, the risk of RSA caused by methylated allele was significantly increased by 7.321 times. Conclusion: MTHFR gene-specific methylation can significantly increase the risk of RSA. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Ulcerative colitis (UC), a chronic inflammatory disease of the colon with unknown etiology, is characterized by remission and recurrence. At present, a considerable number of UC cases are misdiagnosed or delayed in diagnosis and treatment. We aimed to identify UC-related genes to aid the development of drugs for this condition. PATIENTS AND METHODS: Transcriptome data of 362 patients with UC and 126 control subjects were obtained from the Gene Expression Omnibus. The 362 patients with UC were subgrouped using unsupervised machine learning. R software was used to analyze the clinical characteristics of the subgroups, screen subgroup-specific genes, assess the relationships between gene modules and clinical characteristics using weighted gene co-expression network analysis, and perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the subgroups. RESULTS: Patients w ith UC were c lassified into two subgroups. Genes specific to subgroup I included IL21R, ATP8B2, and PLEKHO1. Severe disease tended to be associated with immune cell infiltration; anti-tumor necrosis factor (TNF)-a antibodies and ustekinumab may have been effective in this subgroup. Subgroup II-specific genes included SLC4A4, EPB41L4B, and PLCE1. Patients in this subgroup had mild clinical conditions; however, their disease was more likely to progress to colorectal cancer. Thus, 5-aminosalicylic acid-based drugs may be effective for the treatment of UC in these patients. CONCLUSIONS: We divided UC into two molecular subgroups based on transcriptome data, providing molecular evidence for the development of diagnostic methods and individualized treatment strategies for UC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Transcription factor 7-like 2 (TCF7L2) gene variants confer risk for type 2 diabetes and metabolic traits. We investigated the role of TCF7L2-variants in polycystic ovarian syndrome (PCOS), which is a common endocrine metabolic disorder affecting women of reproductive age. We tested whether TCF7L2 variants are in linkage to and/or in linkage disequilibrium [(LD), namely linkage and association)] with PCOS. PATIENTS AND METHODS: Within 212 families from the Italian peninsular population, we analyzed 78 variants using Pseudomarker software for linkage to and LD with PCOS under the dominant model with complete penetrance (D1). In a secondary analysis, we tested the variants under the recessive models with complete penetrance (R1), dominant with incomplete penetrance (D2), and recessive with incomplete penetrance (R2). We tested through in silico analysis the risk variants to detect any potential functional effects. RESULTS: We identified a total of 14 variants in the TCF7L2 gene significantly linked to and/or in LD with the risk of PCOS (p < 0.05) across different models. CONCLUSIONS: This study is the first to report TCF7L2 linkage and linkage disequilibrium in Italian families with PCOS. [ABSTRACT FROM AUTHOR]

Objective: Some employees tend to eat less healthy food when under work stress, while others tend to maintain a healthy diet. The factors underlying these different dietary choices are not yet clear. Individual differences in people's reactions to environmental stress may help explain this phenomenon. This study proposed a Gene× Stress interaction model of dietary choice, suggesting that different dietary choices under stress may be related to DRD2 genes, which moderate the reward circuitry and have been associated with habitual use of alcohol, obesity, and eating behaviors. Method: 12,269 employees completed genotyping of their saliva samples and questionnaires on work stress, healthy dietary intentions, and healthy dietary behaviors. Nonlinear multiple regressionswere used to test the hypothesized interaction of DRD2 genes and work stress on healthy dietary intentions and healthy dietary behaviors. Results: Individuals with higher work stress reported lower healthy dietary intentions, whereas healthy dietary behaviors exhibited an inverted U shape. DRD2 genes significantly moderated this relationship, and the above relationship was only detected among C allele carriers, whereas for the AA genotype, work stress was not associated with healthy dietary intentions or behaviors. Conclusions: Healthy dietary intentions and healthy dietary behaviors showed different patterns of association with work stress. The DRD2 genes helped explain the individual differences in dietary choice under work stress. [ABSTRACT FROM AUTHOR]

This study aims to use a bibliometric technique to evaluate the scientific output of gene and bipolar disorder research. The search query related to gene and bipolar disorder from the Scopus database identified 1848 documents from 1951 to 2020. The growth in the publications increased since early 1990, peaked in 2011, and started to decline thereafter. High occurrence in author keywords suggests that some research topics, such as "polymorphism", "linkage" and "association study" have waned over time, whereas others, such as "DNA methylation," "circadian rhythm," "" and "meta-analysis," are now the emerging trends in gene and bipolar disorder research. The USA was the country with the highest production followed by the UK, Canada, Italy and Germany. The leading institutions were Cardiff University in the UK, the National Institute of Mental Health (NIMH) in the USA, King's College London in the UK and the University of California, San Diego in the USA. The leading journals publishing gene and bipolar literature were the American Journal of Medical Genetics Neuropsychiatric Genetics, Molecular Psychiatry and Psychiatric Genetics. The top authors in the number of publications were Craddock N, Serretti A and Rietschel M. According to the co-authorship network analysis of authors, the majority of the authors in the same clusters were closely linked together and originated from the same or neighbouring country. The findings of this study may be useful in identifying emerging topics for future research and promoting research collaboration in the field of genetic studies related to bipolar disorder. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Melatonin regulates the mammalian circadian rhythm and plays metabolic functions such as glucose homeostasis. Both melatonin receptors (MTNR1A and MTNR1B, encoded by the MTNR1A and MTNR1B genes, respectively) are expressed in pancreatic beta cells and mediate the glucometabolic roles of melatonin as well as insulin secretion. The MTNR1B gene is a well-known genetic risk factor in type 2 diabetes (T2D); however, little is known about the involvement of the MTNR1A gene in here T2D. We aimed to investigate whether MTNR1A is linked to and/or associated with familial T2D. SUBJECTS AND METHODS: We genotyped 14 single nucleotide polymorphisms within the MTNR1A gene in 212 peninsular Italian families with T2D. We performed parametric linkage and linkage disequilibrium analyses to investigate the role of MTNR1A variants in conferring T2D risk. We considered variants statistically significant if conferring linkage or linkage disequilibrium with p < 0.05. RESULTS: We found 3 novel variants (rs62350392, rs2119883, and rs13147179) significantly linked to and/or associated with T2D in multigenerational Italian families. CONCLUSIONS: This is the first study to report MTNR1A as a novel risk gene in T2D. Functional studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

PYCR2 gene variants are extremely rare condition which is associated with hypomyelinating leukodystrophy type 10 with microcephaly (HLD10). The aim of the present study is to report the clinical findings of patients having novel PYCR2 gene variant that manifest Hereditary Spastic Paraplegia (HSP) is the only symptom without hypomyelinating leukodystrophy. This is the first study that report the PYCR2 gene variants as a cause of HSP in late childhood. We believe it can contribute to expanding the spectrum of the phenotypes associated with PYCR2. It is a retrospective study. Of the patients with similar clinical features from two related families, "patient 1" was designated as the index case, and was analyzed using Whole Exome Squence analysis (WES). The detected variation was investigated in the index case's parents, relatives, and sibling with a similar phenotype. Clinical, brain magnetic resonance (MR) images and MR spectroscopic findings of the patients were reported. A novel homozygous missense (NM_013328: c.383T > C, p.V128A) variant in the PYCR2 gene is detected in 5 patient from 2 related families. All the patients were male, their ages ranges from 6 to 26 years (15.58 ± 8,33 yrs). Developmantal milestones were normal without dysmorphic features. 4 (%80) patients exhibit mild intention tremor started at the age of approximately 6 years of age. 4 (%80) patients had gait difficulty and progressive lower limb spasticity started at the age of 8–12 years. White matter myelination was normal in all patients. Glycine peakes were detected on the MR spectroscopy in all patients. Some variants of PYCR2 gene are responsible for causing clinical features of HSP without hypomyelinating leukodystrophy in the pediatric patients. • PYCR2 gene variants can cause Hereditary Spastic Paraplegia (SPG) in the late childhood period. • Normal Brain MRI can de seen in PYCR2 gene variants although they are associated with hypomyelinating leukodystrophy type 10. • MR spectroscopy findings are helpful for diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Alcohol dependence accounts for a large proportion of the global burden of disease and disability. This study aims to investigate the candidate genes and chemicals associated with alcohol dependence. Methods: Using data from published alcohol dependence genome-wide association studies, we first conducted a proteome-wide association study of alcohol dependence by integrating alcohol dependence genome-wide association studies with 2 human brain reference proteomes of dorsolateral prefrontal cortex from the Religious Order Study and Rush Memory and Aging Project and the Banner Sun Health Research Institute. Then, based on the identified genes in proteome-wide association study, we conducted functional enrichment analysis and chemical-related functional enrichment analysis to detect the related Gene Ontology terms and chemicals. Results: Proteome-wide association study identified several potential candidate genes for alcohol dependence, such as GOT2 (P = 7.59 × 10−6) and C3orf33 (P = 5.00 × 10−3). Furthermore, functional enrichment analysis identified multiple candidate Gene Ontology terms associated with alcohol dependence, such as glyoxylate metabolic process (adjusted P = 2.99 × 10−6) and oxoglutarate metabolic process (adjusted P = 9.95 × 10−6). Chemical-related functional enrichment analysis detected several alcohol dependence–related candidate chemicals, such as pitavastatin (P = 2.00 × 10−4), cannabinoids (P = 4.00 × 10−4), 11-nor-Δ(9)-tetrahydrocannabinol-9-carboxylic acid (P = 4.00 × 10−4), and gabapentin (P = 2.00 × 10−3). Conclusions: Our study reports multiple candidate genes and chemicals associated with alcohol dependence, providing novel clues for understanding the biological mechanism of alcohol dependence. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a complex heterogeneous condition that affects women of reproductive age, conferring increased cardiovascular morbidity and mortality. The syndrome is characterized by oligomenorrhea, hyperandrogenism, and/or polycystic ovaries and is often associated with obesity and type 2 diabetes. Individuals are predisposed to PCOS by environmental factors and risk variants in genes mostly involved in ovarian steroidogenesis and/or insulin resistance. Genetic risk factors have been identified by both familial and genome-wide (GW) association studies. However, most genetic components are still unknown and missing heritability needs to be elucidated. To learn more about the genetic determinants of PCOS, we performed a GW study in genetically highly homogeneous peninsular families. PATIENTS AND METHODS: We conducted the first GW-linkage and linkage disequilibrium (i.e., linkage + association) study in Italian families with PCOS. RESULTS: We identified several novel risk variants, genes, and pathways potentially implicated in the pathogenesis of PCOS. Specifically, we detected 79 novel variants with significant GW-linkage and/or -association with PCOS across 4 inheritance models (p < 0.00005), of which 50 variants were within 45 novel PCOS-risk genes. CONCLUSIONS: This is the first GW-linkage and linkage disequilibrium study performed in peninsular Italian families and reporting novel genes in PCOS. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Oxytocin (OXT) controls appetite, promotes diet-induced energy expenditure, and may protect against obesity. Furthermore, the oxytocin system controls ovarian follicle luteinization and steroidogenesis as well as adrenal steroidogenesis, which if impaired might lead to anovulation and hyperandrogenism, signs found in women with polycystic ovarian syndrome (PCOS). PCOS is a common complex endocrine disorder of reproductive-age women, and it often presents with impaired glucose metabolism, insulin resistance (IR), and type 2 diabetes (T2D). The oxytocin receptor gene (OXTR) may confer a risk for PCOS, conceivably through dysregulation of metabolism, ovarian follicle maturation, and ovarian and adrenal steroidogenesis. Therefore, we aimed to investigate whether OXTR variants confer risk for PCOS. SUBJECTS AND METHODS: In 212 Italian subjects with T2D and PCOS, we have analyzed 22 single nucleotide polymorphisms (SNPs) within the OXTR gene for linkage to and/or linkage disequilibrium (LD, i.e., association) with PCOS. We tested whether the significant risk variants were independent or part of an LD block. RESULTS: We found 5 independent variants significantly linked to/in LD with PCOS within the peninsular families. CONCLUSIONS: This is the first study to report OXTR as a novel risk gene in PCOS. Functional and replication studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Nonpharmacological antidepressant treatments are effective and well tolerated in selected patients. However, response is heterogeneous and validated biomarkers would be precious to aid treatment choice. We searched Pubmed, Scopus, and Google Scholar until May 2022 for original articles evaluating the association of genetic variables with the efficacy of nonpharmacological treatments for major depressive episodes. Most studies analyzed small sample sizes using the candidate gene approach, leading to poorly replicated findings that need to be interpreted cautiously. The few available methylome-wide and genome-wide association studies (GWASs) considered only electroconvulsive therapy (ECT) and cognitive-behavioral therapy in small samples, providing interesting findings by using polygenic risk scores. A deeper knowledge of the genetic factors implicated in treatment response may lead to a better understanding of the neurobiological mechanisms of nonpharmacological therapies for depression, and depression itself. Future GWAS are going to expand their sample size, thanks to consortia such as the gen-ECT-ic consortium. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Alterations in the activity of the transcription factor 7-like 2 (TCF7L2) generate defects previously associated with neuropsychiatric disorders. We investigated the role of the TCF7L2 gene in major depressive disorder (MDD), type 2 diabetes (T2D), and MDD-T2D comorbidity. We tested whether TCF7L2 is in linkage to and/or in linkage disequilibrium (LD, namely association) with MDD, T2D, and MDD-T2D. PATIENTS AND METHODS: In 212 families with T2D and MDD in the Italian population, we analyzed 80 microarray-based SNPs using Pseudomarker software for linkage to and LD with T2D and MDD under the recessive model with complete penetrance (R1). In a secondary analysis, we tested the variants under the dominant models with complete penetrance (D1), recessive with incomplete penetrance (R2), and recessive with incomplete penetrance (R2). RESULTS: We found several novel linkage signals and genetic associations. In addition, we found two new transcription-factor (TF) binding sites created by two risk variants found: the MDD-risk variant rs12255179 creates a new TF-binding site for the CCAAT/enhancer-binding protein α (C/EBPα), and the T2D-risk variant rs61872794 creates a new TF-binding site for the organic cation-uptake transporter (OCT1). Both new binding sites are related to insulin metabolism. CONCLUSIONS: These results highlight the cross-interactivity between T2D and MDD. Further replication is needed in diverse ethnic groups. [ABSTRACT FROM AUTHOR]

Familial transmission is observed in approximately 10% of cases with type 1 diabetes mellitus (T1DM). The most important gene determining susceptibility is the human leukocyte antigen complex (HLA) located on chromosome 6. More than 50 susceptible loci are associated with T1DM susceptibility have been identified in genes other than HLA. In this study, it was aimed to investigate the molecular genetic etiology by whole-exome sequence (WES) analysis in cases with familial T1DM with no or weakly detected HLA tissue type susceptibility. We aimed to identify new genes responsible for the development of type 1 diabetes and to reveal new genes that have not been shown in the literature before. Cases with at least one T1DM diagnosis in first-degree relatives were included in the study. In the first step, HLA DQ2 and DQ8 loci, which are known to be associated with T1DM susceptibility, were investigated by. In the second step, the presence of variants that could explain the situation was investigated by WES analysis in patients who were negative for both HLA DQ2 and HLA DQ8 haplotypes, HLA DQ2 negative, HLA DQ8 positive, and HLA DQ2 positive and HLA DQ8 negative patients. The mean age and duration of diabetes of the 30 cases (Girl/Male: 17/13) were 14.9 ± 6 and 7.56 ± 3.84 years, respectively. There was consanguineous marriage in 5 (16%) of the families. As a result of filtering all exome sequence analysis data of two cases with DQ2 (DQB1*02) (−) and DQ8 (DQB1*03:02) (−), seven cases with DQ2 (DQB1*02) (+) and DQ8 (DQB1*03:02) (−), and one case with DQ2 (DQB1*02) (−) and DQ8 (DQB1*03:02) (+), seven different variants in seven different genes were detected in five cases. The pathogenicity of the detected variants were determined according to the "American College of Medical Genetics and Genomics (ACMG)" criteria. These seven variants detected were evaluated as high-score VUS (Variants of unknown/uncertain significance). In the segregation study conducted for the mutation in the POLG gene detected in case 5, this variant was detected in the mother of the case and his brother with T1DM. Segregation studies are ongoing for variants detected in other affected individuals in the family. In conclusion, in this study, seven different variants in seven different genes were detected in five patients by WES analysis in familial T1DM patients with no or weak HLA tissue type susceptibility. These seven variants detected were evaluated as high-score VUS. POLG might be a novel candidate gene responsible for susceptibility to T1DM. Non-HLA genes directly responsible for the development of T1DM were not detected in any of the cases. [ABSTRACT FROM AUTHOR]

Objectives Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in children that lead to numerous complications. This study examined the changes in rs2283265 polymorphisms in the dopamine receptor D2 (DRD2) and rs27072 in the dopamine transporter gene (SLC6A3) in ADHD patients. Materials & Methods This descriptive-analytical study was performed on children aged 4-12 years with ADHD. In this study, 100 patients in the ADHD group (according to DSM-IV-TR criteria and diagnosed by interview by a child and adolescent psychiatrist) and 100 children in the control group (including patients referring to the pediatrician without hyperactivity) were enrolled. Two polymorphisms rs2283265 and rs27072 in two groups were comparatively investigated using PCR-RFLP method and restriction enzymes. Data were analyzed using SPSS 17. Results There was a significant correlation between gender and ADHD, and the disease was more common in boys (P=0.021). In this study, there was no significant relationship between ADHD types and frequency distribution of rs2283265 (DRD2) and rs27072 (SLC6A3) polymorphism genotypes (P<0.05). However, there was a significant correlation between distribution of rs2283265 (DRD2) and rs27072 (SLC6A3) polymorphisms and ADHD (P<0.05). Conclusion It seems that the changes in DRD2 and SLC6A3 genes are associated with ADHD, and study of these genes can be helpful in diagnosis and genetic screening. [ABSTRACT FROM AUTHOR]

Background. Acromegaly is a disorder associated with hypersecretion of growth hormone, most usually caused by a pituitary adenoma. Dysmotility of the gastrointestinal tract has been reported in acromegalic patients. Achalasia is a disorder characterized by aperistalsis of the oesophagus with incomplete lower oesophageal sphincter relaxation and whose aetiology remains unknown. Mutations in some genes have previously been associated with the development of acromegaly or achalasia. The study aims were to analyse mutations in selected genes in a woman having both of these diseases, to identify their aetiological factors, and to suggest explanations for the co-incidence of acromegaly and achalasia. Methods and Results. A female patient with acromegaly, achalasia, and a multinodular thyroid gland with hyperplastic colloid nodules underwent successful treatment of achalasia via laparoscopic Heller myotomy, a thyroidectomy was performed, and the pituitary macroadenoma was surgically excised via transnasal endoscopic extirpation. Germline DNA from the leukocytes was analysed by sequencing methods for a panel of genes. No pathogenic mutation in AAAS, AIP, MEN1, CDKN1B, PRKAR1A, SDHB, GPR101, and GNAS genes was found in germline DNA. The somatic mutation c.601C>T/p. R201C in the GNAS gene was identified in DNA extracted from a tissue sample of the pituitary macroadenoma. Conclusions. We here describe the first case report to our knowledge of a patient with both acromegaly and achalasia. Association of acromegaly and soft muscle tissue hypertrophy may contribute to achalasia's development. If one of these diagnoses is determined, the other also should be considered along with increased risk of oesophageal and colorectal malignancy. [ABSTRACT FROM AUTHOR]

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder influenced by genetic and environmental factors. This study examined the specific gene variants, dopamine transporter 1 (DAT1) rs6350, dopamine receptor D3 (DRD3) rs6280, dopamine receptor D2 (DRD2) rs6277, and catechol-O-methyltransferase (COMT) rs4633, in relation to ADHD among Pakistani children by exploring the potential gene-gene and gene-environment interactions. A total of 100 cases of ADHD and 100 healthy children were recruited. The tetra-primer amplification refractory mutation system (ARMS) assays were designed for genotyping the selected variants in both groups, and their association with ADHD was determined in different genetic models. Gene-gene and gene-environmental interactions were determined by the multifactor dimensionality reduction (MDR) method. The DAT1 rs6350 SNV AA genotype showed a significantly increased risk for ADHD in the codominant and recessive models. Conversely, the AG genotype demonstrated a protective factor for ADHD in the codominant and overdominant models. The DRD3 rs6280 T allele exhibited a decreased risk for ADHD, and the TT genotype showed a reduced risk in the recessive and log-additive models. No association between the DRD2 rs6277 and COMT rs4633 SNVs with ADHD was found in our population. The MDR analysis of the best three-fold interaction model showed redundancy between DAT1 rs6350 and DRD3 rs6280; however, the risk was increased with the gender variable, which showed a weak synergistic interaction with these SNVs. Genes associated with dopaminergic neurotransmission may contribute to the occurrence of ADHD. Furthermore, gene-gene and gene-environmental interactions may increase ADHD susceptibility. [ABSTRACT FROM AUTHOR]

As ectothermic invertebrates, mollusks are regarded as good environmental indicator species for determining the adverse effects of climate change on marine organisms. In the present study, the effects of cold stress on the tissue structure, antioxidant activity, and expression levels of genes were evaluated in the warm-water noble scallop Chlamys nobilis by simulating natural seawater cooled down during winter from 17 °C to 14 °C, 12 °C, 10 °C, and 9 °C. Firstly, the gill was severely damaged at 10 °C and 9 °C, indicating that it could be used as a visually indicative organ for monitoring cold stress. The methylenedioxyamphetamine (MDA) content significantly increased with the temperatures decreasing, meanwhile, the antioxidant enzyme activities superoxide dismutase (SOD) and catalase (CAT) showed a similar pattern, suggesting that the scallop made a positive response. More importantly, 6179 genes related to low temperatures were constructed in a module-gene clustering heat map including 10 modules. Furthermore, three gene modules about membrane lipid metabolism, amino acid metabolism, and molecular defense were identified. Finally, six key genes were verified, and HEATR1 , HSP70B2 , PI3K , and ATP6V1B were significantly upregulated, while WNT6 and SHMT were significantly downregulated under cold stress. This study provides a dynamic demonstration of the major gene pathways' response to various low-temperature stresses from a transcriptomic perspective. The findings shed light on how warm-water bivalves can tolerate cold stress and can help in breeding new strains of aquatic organisms with low-temperature resistance. [Display omitted] • The influence of Chlamys nobilis in cold winters was simulated by chronic cold stress. • The gill can be used as a visually indicative organ for monitoring cold stress. • The gill can make a positive response by increasing SOD and CAT levels under cold stress. • Some pathways and genes related to cold stress were found. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the leading causes of cancer deaths globally. We implemented a comprehensive literature review regarding CRC genetics studies to offer a perception into the genes associated with CRC recognized in Saudi patients. Definite genetic variants in ABCB1, ADIPOQ, CTNNB1, SFRP3, LRP6, CYP19A1, PARP-1, TDG genes exhibited significant protection against CRC development in Saudi population. Whereas, other gene mutations in ABCB1, ABCC1, CASR, IL-17F, NOTCH1, NOTCH4, PRNCR1, TDG, TLR2, TLR4, TLR-9, TSLP, TSLPR and TNF-α genes showed irrelevant correlation with CRC risk in Saudi Arabia. On the other hand, specific mutations in ABCC1, ADIPOQ, CYP1A1, KIR, IL-17A, MMP2, NOTCH3, PRNCR1, RETN, TDG, TLR2, BRAF, PARP-1, TLR4, TLR-9, TNF-α, TSLP and XRCC1 genes demonstrated a substantial augmented CRC risk development in Saudi patients. Furthermore, ATR, ATM, BMI1, CCAT1, Chk1, Chk2, COX-2, FoxM1, FSCN1, Ki67, MALAT1, miR-29, miR-34a, miR-92, miR-182-5, PANDAR, PIK3CA, TIGAR over-expression revealed a robust association with CRC in Saudi Arabia (KSA). Moreover, gene alterations in APC, EGFR, FBXW7, TP53, PTEN, K-ras genes were concomitant in CRC. As well as, lower expression of MLH1, MSH2, MSH6, PMS2, EPCAM and MUTYH genes were recognized in LS patients and future CRC Saudi patients. These gene mutations may be used as diagnostic and/or prognostic genetic markers in CRC Saudi patients and could offer a potential therapeutic target for CRC management. [ABSTRACT FROM AUTHOR]

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Saudi Genome program is a revolutionary nationwide transformation initiative of Saudi Vision 2030. The program goals are to recognize and reduce the incidence of genetic diseases in the Kingdom of Saudi Arabia (KSA). Accordingly, the program will establish the foundation for personalized and genomic medicine in the KSA. Epilepsy has a high prevalence in KSA reaching around 6.54 of 1000 individuals with a subsequent massive financial burden. One of the main risk factors for this high prevalence and associated with increased risk of epilepsy development is consanguinity marriage, which is traditional in KSA. In this review, we executed a comprehensive state-of-art literature review regarding epilepsy genetics to offer a perception into the genes associated with epilepsy recognized in Saudi epileptic patients. Several genes’ mutations were incorporated in this review including AFG3L2, ASPM, ATN1, ATP1A2, BMP5, CCDC88A, C12orf57, DNAJA1, EML1, ERLIN2, FRRS1L, GABRG3, NRXN3, MDH1, KCNJ10, KCNMA1, KCNT1, KIAA0226, OPHN1, PCCA, PCCB, PEX, PGAP2, PI4K2A, PODXL, PRICKLE1, PNKP, RELN, SCN2A, SCN1B, SLC2A1, SLC19A3, SLC25, SIAH1, SYNJ1, SZT2, TBCK, TMX2, TSC1, TSC2, TSEN, WDR45B, WWOX, UBR, UGDH, and YIF1B. For each of these genes, we tried to explain a little about the gene associated proteins and their roles in epilepsy development. [ABSTRACT FROM AUTHOR]

Low epidermal filaggrin (FLG) is a risk factor for atopic dermatitis (AD) and allergic comorbidity. FLG mutations do not fully explain the variation in epidermal FLG levels, highlighting that other genetic loci may also regulate FLG expression. We sought to identify genetic loci that regulate FLG expression and elucidate their functional and mechanistic consequences. A genome-wide association study of quantified skin FLG expression in lesional and baseline non(never)-lesional skin of children with AD in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort was conducted. Clustered regularly interspaced short palindromic repeat approaches were used to create isogenic human keratinocytes differing only at the identified variant rs11652075, and caspase recruitment domain family member 14 (CARD14)-deficient keratinocytes for subsequent mechanistic studies. The genome-wide association study identified the CARD14 rs11652075 variant to be associated with FLG expression in non(never)-lesional skin of children with AD. Rs11652075 is a CARD14 expression quantitative trait locus in human skin and primary human keratinocytes. The T variant destroys a functional cytosine-phosphate-guanine site, resulting in reduced cytosine-phosphate-guanine methylation at this site (but not neighboring sites) in TT and CT compared with CC primary human keratinocytes and Mechanisms of Progression of Atopic Dermatitis to Asthma in Children children's skin samples, and rs11652075 increases CARD14 expression in an allele-specific fashion. Furthermore, studies in clustered regularly interspaced short palindromic repeat-generated CC and TT isogenic keratinocytes, as well as CARD14-haplosufficient and deficient keratinocytes, reveal that IL-17A regulates FLG expression via CARD14, and that the underlying mechanisms are dependent on the rs11652075 genotype. Our study identifies CARD14 as a novel regulator of FLG expression in the skin of children with AD. Furthermore, CARD14 regulates skin FLG homeostasis in an rs11652075-dependent fashion. [ABSTRACT FROM AUTHOR]

[Display omitted] • Traits obtained by high-throughput phenotyping perform similarly or even better in GWAS than those obtained by traditional, manual methods. • Dynamic phenotyping contributing a lot for GWAS to identify time-specific loci. • High-throughput phenotyping, allowing noncontact and dynamic measurement, possesses great potential to provide high quality trait data for GWAS. • Future research should focus on the development of low-cost high-throughput phenotyping techniques and efficiency data/image analysis algorithm. • Research of using various high-throughput phenotyping techniques and GWAS on more diverse plant species and traits is urgently needed. Linking phenotypes and genotypes to identify genetic architectures that regulate important traits is crucial for plant breeding and the development of plant genomics. In recent years, genome-wide association studies (GWASs) have been applied extensively to interpret relationships between genes and traits. Successful GWAS application requires comprehensive genomic and phenotypic data from large populations. Although multiple high-throughput DNA sequencing approaches are available for the generation of genomics data, the capacity to generate high-quality phenotypic data is lagging far behind. Traditional methods for plant phenotyping mostly rely on manual measurements, which are laborious, inaccurate, and time-consuming, greatly impairing the acquisition of phenotypic data from large populations. In contrast, high-throughput phenotyping has unique advantages, facilitating rapid, non-destructive, and high-throughput detection, and, in turn, addressing the shortcomings of traditional methods. Aim of Review: This review summarizes the current status with regard to the integration of high-throughput phenotyping and GWAS in plants, in addition to discussing the inherent challenges and future prospects. Key Scientific Concepts of Review: High-throughput phenotyping, which facilitates non-contact and dynamic measurements, has the potential to offer high-quality trait data for GWAS and, in turn, to enhance the unraveling of genetic structures of complex plant traits. In conclusion, high-throughput phenotyping integration with GWAS could facilitate the revealing of coding information in plant genomes. [ABSTRACT FROM AUTHOR]

Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine important in initiation of allergic inflammation. Single nucleotide polymorphisms (SNPs) in TSLP are associated with asthma, yet studies have shown inconsistent associations between circulating TSLP and asthma. Studies that integrate the combined effects of TSLP genotype, TSLP mRNA, circulating TSLP levels, and asthma outcome are lacking. This study sought to recruit a novel cohort based on asthma-relevant TSLP SNPs and determine their impact on TSLP mRNA expression and TSLP circulating protein levels, and their individual and combined effects on asthma. This study developed an algorithm to prioritize TSLP SNPs and recruited 51 carriers and noncarriers based on TSLP genotypes. TSLP mRNA was quantified in nasal epithelial cells and circulating TSLP levels in plasma. This study determined the associations of defined TSLP risk genotypes and/or TSLP mRNA and protein levels with asthma. TSLP mRNA expression, but not circulating TSLP, was significantly increased in people who are asthmatic compared with in people who are nonasthmatic (P =.007; odds ratio, 1.44). Notably, 90% of children with the defined TSLP risk genotypes and high nasal TSLP mRNA expression (top tertile) had asthma compared with 40% of subjects without risk genotypes and with low TSLP expression (bottom tertile) (P =.024). No association between circulating TSLP and asthma was observed. Collectively, these data suggest childhood asthma is modified by the combined effects of TSLP genotype and TSLP expression in the nasal epithelium. The increased asthma risk likely manifests when genetic variation enables expression quantitative trait loci in the TSLP locus to elevate TSLP. It is important to consider both biomarkers when factoring asthma risk. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVD) are the leading cause of death all over the world. Beside general risk factors, there are some genetic factors which lead to cardiovascular diseases. Various nuclear DNA mutation and also mitochondrial DNA mutations have been related with cardiovascular diseases. In the present study, a total of 21 samples were collected from different families residing in district Dir. DNA was extracted from buccal epithelial cells using saliva. The mitochondrial tRNA leu (MT TL1) gene was amplified by PCR and 10 samples of different families were sequenced. The sequence was aligned with revised Cambridge Reference Sequence (rCRS) accession # NC-012920.1. It is concluded that cardiovascular diseases in our subjects are not due to mutation in the mitochondrial leucine tRNA gene. However, a large population of subjects with cardiovascular diseases needs to be studied and whole mitochondrial DNA is needed to be sequenced in the subjects with CVD. This will give an idea about the probable DNA marker which can be used to prevent loses due to these diseases at a very early stages. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor receptor 2 is a protein encoded by FGFR2 gene and plays an important role in cellular growth. This study was conducted to investigate a potential association of FGFR2 rs2981582 with breast cancer. DNA was obtained from 137 Formalin-fixed, paraffin-embedded tumors and 98 normal breast tissue samples. Genotypes were carried out with PCR-RFLP. The odds ratio and 95% confidence interval (CI) were used to evaluate the power of the associations. A significant association between FGFR2 rs2981582 C allele and susceptibility to breast cancer was found (p-value < 0.0001, Odds Ratio = 2.3, %95 CI (1.5–3.0). No significant differences in FGFR2 rs2981582 genotypes and alleles distribution among breast patients with different hormonal receptor status (p > 0.05) were detected. However, a significant difference was found in genotypes and alleles distribution in ER+, PR- and HER2 between breast cancer cases and controls. This study showed an association of FGFR2 rs2981582T/C with breast cancer in Saudi women, further large study is required to validate the results. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Depression is moderately heritable but there is no common genetic variant which has a major effect on susceptibility. A previous analysis of 50 000 exome-sequenced subjects failed to implicate any genes or sets of genes in which rare variants were associated with risk of affective disorder requiring specialist treatment. A much larger exome-sequenced dataset is now available. Methods: Data from 200 632 exome-sequenced UK Biobank participants was analysed. Subjects were treated as cases if they had reported having seen a psychiatrist for 'nerves, anxiety, tension or depression'. Gene-wise weighted burden analysis was performed to see if there were any genes or sets of genes for which there was an excess of rare, functional variants in cases. Results: There were 22 886 cases and 176 486 controls. There were 22 642 informative genes but no gene or gene set produced a statistically significant result after correction for multiple testing. None of the genes or gene sets with the lowest P values appeared to be an obvious biological candidate. Conclusions: The results conform exactly with the expectation under the null hypothesis. It seems unlikely that the use of common, poorly defined phenotypes will produce useful advances in understanding genetic contributions to affective disorder and it might be preferable to focus instead on obtaining large exome-sequenced samples of conditions such as bipolar 1 disorder and severe, recurrent depression. This research has been conducted using the UK Biobank Resource. [ABSTRACT FROM AUTHOR]

Copyright of Turk Psikiyatri Dergisi is the property of Turk Psikiyatri Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Different genes and loci that are associated with non-syndromic developmental tooth agenesis (TA) have the same causation pathway in the development of tumours including breast cancer (BC), epithelial ovarian cancer (EOC), colorectal cancer (CRC) and lung cancer (LC). To assess the link between TA and the development of cancer. This registered review included a comprehensive search of electronic databases (Cochrane Central Register of Controlled Trials [CENTRAL], LILACS, Scopus, Web of Science and Medline via Ovid) until 1 April 2020, supplemented by manual, grey literature and reference lists search. There was no restriction in term of date of publication, gender, race or type of hypodontia. The primary outcome was the relationship between TA and cancer. The secondary outcome was to identify the genetic correlation between TA and cancer. Study selection, data extraction and risk of bias assessment were performed independently and induplicate by two reviewers, with disputes resolved by a third reviewer. Eight studies with a moderate-high risk of bias were included in the final review, with a total of 5821 participants. Due to the heterogeneity among the included studies, the data were presented narratively. Limited studies reported a high prevalence of EOC (19.2%–20%) and CRC (82%–100%) in individuals with TA (depending on the study) compared to those without TA (3% for EOC and 0% for CRC). While others reported a weak correlation between EOC and CRC and TA (P > 0.05). Weak evidence suggested a strong correlation between breast, cervical uterine and prostate cancers and TA (P < 0.05). Though low-quality evidence suggests a link between TA and cancer, it was not possible to verify that TA can hold a predictive value as a marker for cancers. Further research is needed to confirm the association. PROSPERO (CRD42020139751). [ABSTRACT FROM AUTHOR]

Whole genome and exome sequencing (WGS/WES) are the most popular next‐generation sequencing (NGS) methodologies and are at present often used to detect rare and common genetic variants of clinical significance. We emphasize that automated sequence data processing, management, and visualization should be an indispensable component of modern WGS and WES data analysis for sequence assembly, variant detection (SNPs, SVs), imputation, and resolution of haplotypes. In this manuscript, we present a newly developed findable, accessible, interoperable, and reusable (FAIR) bioinformatics‐genomics pipeline Java based Whole Genome/Exome Sequence Data Processing Pipeline (JWES) for efficient variant discovery and interpretation, and big data modeling and visualization. JWES is a cross‐platform, user‐friendly, product line application, that entails three modules: (a) data processing, (b) storage, and (c) visualization. The data processing module performs a series of different tasks for variant calling, the data storage module efficiently manages high‐volume gene‐variant data, and the data visualization module supports variant data interpretation with Circos graphs. The performance of JWES was tested and validated in‐house with different experiments, using Microsoft Windows, macOS Big Sur, and UNIX operating systems. JWES is an open‐source and freely available pipeline, allowing scientists to take full advantage of all the computing resources available, without requiring much computer science knowledge. We have successfully applied JWES for processing, management, and gene‐variant discovery, annotation, prediction, and genotyping of WGS and WES data to analyze variable complex disorders. In summary, we report the performance of JWES with some reproducible case studies, using open access and in‐house generated, high‐quality datasets. [ABSTRACT FROM AUTHOR]