20,351 results match your criteria genetic setting

Rare variants in KDR, encoding VEGF Receptor 2, are associated with tetralogy of Fallot.

Genet Med 2021 Jun 10. Epub 2021 Jun 10.

University of Nottingham, Queen's Medical Centre, Nottingham, UK.

Purpose: Rare genetic variants in KDR, encoding the vascular endothelial growth factor receptor 2 (VEGFR2), have been reported in patients with tetralogy of Fallot (TOF). However, their role in disease causality and pathogenesis remains unclear.

Methods: We conducted exome sequencing in a familial case of TOF and large-scale genetic studies, including burden testing, in >1,500 patients with TOF. Read More

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Applied shotgun metagenomics approach for the genetic characterization of dengue viruses.

J Biotechnol 2019 15;306S:100009. Epub 2019 May 15.

University of Groningen, University Medical Center Groningen, Department of Medical Microbiology and Infection Prevention, Groningen, the Netherlands. Electronic address:

Dengue virus (DENV), an arthropod-borne virus, has rapidly spread in recent years. DENV diagnosis is performed through virus serology, isolation or molecular detection, while genotyping is usually done through Sanger sequencing of the envelope gene. This study aimed to optimize the use of shotgun metagenomics and subsequent bioinformatics analysis to detect and type DENV directly from clinical samples without targeted amplification. Read More

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Epidemiology and Genetics of Venous Thromboembolism and Chronic Venous Disease.

Circ Res 2021 Jun 10;128(12):1988-2002. Epub 2021 Jun 10.

Department of Surgery, Division of Vascular Surgery, Stanford University School of Medicine, CA (R.A.B., E.F.).

Venous disease is a term that broadly covers both venous thromboembolic disease and chronic venous disease. The basic pathophysiology of venous thromboembolism and chronic venous disease differ as venous thromboembolism results from an imbalance of hemostasis and thrombosis while chronic venous disease occurs in the setting of tissue damage because of prolonged venous hypertension. Both diseases are common and account for significant mortality and morbidity, respectively, and collectively make up a large health care burden. Read More

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Improving Genomic Prediction Using High-Dimensional Secondary Phenotypes.

Front Genet 2021 24;12:667358. Epub 2021 May 24.

Biometris, Wageningen University and Research, Wageningen, Netherlands.

In the past decades, genomic prediction has had a large impact on plant breeding. Given the current advances of high-throughput phenotyping and sequencing technologies, it is increasingly common to observe a large number of traits, in addition to the target trait of interest. This raises the important question whether these additional or "secondary" traits can be used to improve genomic prediction for the target trait. Read More

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Fumarate Hydratase Deficiency Should be Considered in the Differential Diagnosis of Uterine and Extrauterine Smooth Muscle Tumors of Uncertain Malignant Potential (STUMP).

Int J Gynecol Pathol 2021 Jun 9. Epub 2021 Jun 9.

Department of Pathology, Stanford University School of Medicine, Stanford, California.

Fumarate hydratase-deficient leiomyomas (dFH leiomyomas) often display atypical pathologic features yet exhibit a benign clinical course. Recent data suggest that dFH leiomyomas may be misclassified as smooth muscle tumors of uncertain malignant potential, a category that encompasses a heterogenous subgroup of uterine neoplasms with smooth muscle differentiation and atypical features that impart ambiguity regarding their expected clinical behavior. dFH leiomyomas can be seen in the context of hereditary leiomyomatosis and renal cell carcinoma syndrome or in the sporadic setting. Read More

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Sex-specific genetic (co)variances of standard metabolic rate, body mass and locomotor activity in Drosophila melanogaster.

J Evol Biol 2021 Jun 9. Epub 2021 Jun 9.

Department of Biology, University of Ottawa, Ottawa, ON, Canada.

A longstanding focus in evolutionary physiology concerns the causes and consequences of variation in maintenance metabolism. Insight into this can be gained by estimating the sex-specific genetic architecture of maintenance metabolism alongside other, potentially correlated traits on which selection may also act, such as body mass and locomotor activity. This may reveal potential genetic constraints affecting the evolution of maintenance metabolism. Read More

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Association of Diet Quality With Prevalence of Clonal Hematopoiesis and Adverse Cardiovascular Events.

JAMA Cardiol 2021 Jun 9. Epub 2021 Jun 9.

Cardiovascular Research Center, Massachusetts General Hospital, Boston.

Importance: Clonal hematopoiesis of indeterminate potential (CHIP), the expansion of somatic leukemogenic variations in hematopoietic stem cells, has been associated with atherosclerotic cardiovascular disease. Because the inherited risk of developing CHIP is low, lifestyle elements such as dietary factors may be associated with the development and outcomes of CHIP.

Objective: To examine whether there is an association between diet quality and the prevalence of CHIP. Read More

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Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals: Findings From the RHDGen Study.

JAMA Cardiol 2021 Jun 9. Epub 2021 Jun 9.

Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.

Importance: Rheumatic heart disease (RHD), a sequela of rheumatic fever characterized by permanent heart valve damage, is the leading cause of cardiac surgery in Africa. However, its pathophysiologic characteristics and genetics are poorly understood. Understanding genetic susceptibility may aid in prevention, control, and interventions to eliminate RHD. Read More

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A Case Report of Recurrent Hypokalemia During Pregnancies Associated With Nonaldosterone-Mediated Renal Potassium Loss.

Can J Kidney Health Dis 2021 28;8:20543581211017424. Epub 2021 May 28.

Medical University of South Carolina, College of Medicine, Charleston, SC, USA.

Rationale: Geller et al reported a rare mutation in the mineralocorticoid receptor (MR) resulting in constitutive MR activity. Progesterone, normally an MR antagonist, acts as a potent agonist with this mutation. Progesterone levels can increase 100-fold during pregnancy and thus lead to increased MR activity in this setting, resulting in hypertension (HTN) and hypokalemia during pregnancy and resolution of hypokalemia after delivery. Read More

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Calcium: More Than Bone? Implications for Clinical Practice and Theory.

J Clin Med Res 2021 May 25;13(5):253-257. Epub 2021 May 25.

South Bay Institute of Clinical Research, University of California, Berkeley, CA, USA.

Serum calcium is routinely screened, but rarely scrutinized in the context of normal, physiologic functioning. This brief review strives to explore the implications of serum calcium, suggests guidelines for its interpretation, and discusses the implications of high, low, and "normocalcemia" in the clinical setting. We find that serum Ca concentrations are a valuable prognostic indicator in routine metabolic workups and advocate for greater attention, on behalf of the provider, to variations in a patient's calcemic status. Read More

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Improving the efficacy of exome sequencing at a quaternary care referral centre: novel mutations, clinical presentations and diagnostic challenges in rare neurogenetic diseases.

J Neurol Neurosurg Psychiatry 2021 Jun 8. Epub 2021 Jun 8.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Background: We used a multimodal approach including detailed phenotyping, whole exome sequencing (WES) and candidate gene filters to diagnose rare neurological diseases in individuals referred by tertiary neurology centres.

Methods: WES was performed on 66 individuals with neurogenetic diseases using candidate gene filters and stringent algorithms for assessing sequence variants. Pathogenic or likely pathogenic missense variants were interpreted using in silico prediction tools, family segregation analysis, previous publications of disease association and relevant biological assays. Read More

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Elucidating Prostate Cancer Behaviour During Treatment via Low-pass Whole-genome Sequencing of Circulating Tumour DNA.

Eur Urol 2021 Jun 5. Epub 2021 Jun 5.

The Institute of Cancer Research, University of London, London, UK; The Royal Marsden Hospital, London, UK.

Background: Better blood tests to elucidate the behaviour of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed to drive therapeutic decisions. Plasma cell-free DNA (cfDNA) comprises normal and circulating tumour DNA (ctDNA). Low-pass whole-genome sequencing (lpWGS) of ctDNA can provide information on mCRPC behaviour. Read More

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Vascular-immuno-phenotypic (VIP) model for locally advanced and oligo-metastatic cancer: A hypothesis.

Kumara Swamy

Med Hypotheses 2021 May 27;152:110618. Epub 2021 May 27.

Consultant and Head Radiation Oncology, Aster CMI, #43/2, New Airport Road, Sahakar Nagar, Bangalore 560 092, India. Electronic address:

Primary Hypothesis: In cancer therapy, normalization of the vasculature, and not disruption, to facilitate the reversal of the immuno-phenotypic changes, is the sine-qua-non for cancer elimination. The triad of normalization of the vasculature, leading to the improved immunological tumour microenvironment and increased susceptibility of resistant phenotypic cancer cells (VIP model), forms the basis of this hypothesis. This article hypothesizes the absolute need for vascular normalization for the eradication of cancer. Read More

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Intrauterine growth restriction followed by oxygen support uniquely interferes with genetic regulators of myelination.

eNeuro 2021 Jun 7. Epub 2021 Jun 7.

Children's Hospital of Chicago, Department of Pediatrics, Division of Neonatology, Chicago, Illinois, USA.

Intrauterine growth restriction (IUGR) and oxygen exposure in isolation and combination adversely affect the developing brain, putting infants at risk for neurodevelopmental disability including cerebral palsy. Rodent models of IUGR and postnatal hyperoxia have demonstrated oligodendroglial injury with subsequent white matter injury (WMI) and motor dysfunction. Here we investigate transcriptomic dysregulation in IUGR with and without hyperoxia exposure to account for the abnormal brain structure and function previously documented. Read More

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Practical implementation of genetic groups in single-step genomic evaluations with Woodbury matrix identity-based genomic relationship inverse.

J Dairy Sci 2021 Jun 4. Epub 2021 Jun 4.

Natural Resources Institute Finland (Luke), FI-31600 Jokioinen, Finland.

The growing amount of genomic information in dairy cattle has increased computational and modeling challenges in the single-step evaluations. The computational challenges are due to the dense inverses of genomic (G) and pedigree (A) relationship matrices of genotyped animals in the single-step mixed model equations. An equivalent mixed model equation is given by single-step genomic BLUP that are based on the T matrix (ssGTBLUP), where these inverses are avoided by expressing G through a product of 2 rectangular matrices, and (A) through sparse matrix blocks of the inverse of full relationship matrix A. Read More

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-Related Frontonasal Dysplasias: Clinical Characteristics and Surgical Management.

Cleft Palate Craniofac J 2021 Jun 8:10556656211019621. Epub 2021 Jun 8.

37515Hacettepe University Faculty of Medicine, Department of Plastic, Reconstructive and Aesthetic Surgery, Ankara, Turkey.

Aim: The term frontonasal dysplasia (FND) represents a spectrum of anomalies and its genetics have not been well defined. Recently, the critical role of the aristaless-like homeobox () gene family on the craniofacial development has been discovered. In the present study, we aimed to propose a systematic surgical treatment plan for the -related FNDs according to the genotypic classification as well as demonstrating their clinical characteristics to help surgeons diagnose the underlying pathology accurately. Read More

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A Mendelian Randomization Approach Using 3-HMG-Coenzyme-A Reductase Gene Variation to Evaluate the Association of Statin-Induced Low-Density Lipoprotein Cholesterol Lowering With Noncardiovascular Disease Phenotypes.

JAMA Netw Open 2021 Jun 1;4(6):e2112820. Epub 2021 Jun 1.

Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Importance: Observational studies suggest that statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, may be associated with beneficial effects in many noncardiovascular diseases.

Objective: To construct a weighted HMG-CoA reductase (HMGCR) gene genetic risk score (GRS) using variants in the HMGCR gene affecting low-density lipoprotein cholesterol as an instrumental variable for mendelian randomization analyses to test associations with candidate noncardiovascular phenotypes previously associated with statin use in observational studies.

Design, Setting, And Participants: This cohort study included 53 385 unrelated adults of European ancestry with genome-wide genotypes available from BioVU (a practice-based biobank, used for discovery) and 30 444 unrelated adults with European ancestry available in the Electronic Medical Records and Genomics (eMERGE; a research consortium that conducts genetic research using electronic medical records, used for replication). Read More

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Clinical Utility of Whole Exome Sequencing and Targeted Panels for the Identification of Inborn Errors of Immunity in a Resource-Constrained Setting.

Front Immunol 2021 21;12:665621. Epub 2021 May 21.

SAMRC Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Primary immunodeficiency disorders (PIDs) are inborn errors of immunity (IEI) that cause immune system impairment. To date, more than 400 single-gene IEI have been well defined. The advent of next generation sequencing (NGS) technologies has improved clinical diagnosis and allowed for discovery of novel genes and variants associated with IEI. Read More

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Combined exome sequencing and deep phenotyping in highly selected fetuses with skeletal dysplasia during the first and second trimesters improves diagnostic yield.

Prenat Diagn 2021 Jun 6. Epub 2021 Jun 6.

Department of Obstetrics and Gynecology, 1st Medical Center of Chinese PLA General Hospital, Beijing, China.

Objective: To investigate the genetic etiology of skeletal dysplasia in highly selected fetuses during the first and second trimesters using deep phenotyping and exome sequencing (ES).

Method: Fetuses with short femurs were identified using the established prenatal diagnostic approach. A multidisciplinary team reviewed fetal phenotypic information (prenatal ultrasound findings, fetal postmortem, and radiographs) in a cohort of highly selected fetuses with skeletal dysplasia during the first and second trimesters. Read More

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Keratoconus concordance in monozygotic twins before and after combined CXL/PRK (Athens Protocol) using Scheimflung and OCT tomography.

J Cataract Refract Surg 2021 May 10. Epub 2021 May 10.

: LaserVision Clinical & Research Eye Institute, Athens, Greece : New York University Medical School, NY, NY.

Pupose: To describe the concordance of keratoconus expression in two pairs of monozygotic twins before and after a combined CXL/PRK procedure.

Setting: Private Ambulatory Eye Surgery Unit.

Design: Retrospective Interventional Twin Study. Read More

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Development of decision aids for female BRCA1 and BRCA2 mutation carriers in Germany to support preference-sensitive decision-making.

BMC Med Inform Decis Mak 2021 06 5;21(1):180. Epub 2021 Jun 5.

Institute for Health Economics and Clinical Epidemiology, The University Hospital of Cologne, Gleueler Straße 176-178, 50935, Cologne, Germany.

Background: Women with pathogenic BRCA1 and BRCA2 mutations possess a high risk of developing breast and ovarian cancer. They face difficult choices when considering preventive options. This study presents the development process of the first decision aids to support this complex decision-making process in the German healthcare system. Read More

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Polygenic Risk Scores Stratify Keratinocyte Cancer Risk among Solid Organ Transplant Recipients with Chronic Immunosuppression in a High Ultraviolet Radiation Environment.

J Invest Dermatol 2021 Jun 2. Epub 2021 Jun 2.

Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Australia; School of Biomedical Sciences, Faculty of Health, and Centre for Genomics and Personalised Health, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove QLD 4059, Australia.

Solid organ transplant recipients (SOTRs) have elevated risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), especially in high ultraviolet (UV) radiation environments. We assessed whether polygenic risk scores (PRSs) can improve prediction of BCC and SCC risks and multiplicity over and above traditional risk factors in SOTRs in a high UV setting. We built PRSs for BCC (N=594,881) and SCC (N=581,431) using UK Biobank and 23andMe datasets, validated them in the Australian QSkin Cohort (N>6,300) and applied them in SOTRs in the STAR Cohort from Queensland, Australia, a high UV environment. Read More

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SNPs at 3'UTR of APOL1 and miR-6741-3p target sites associated with kidney diseases more susceptible to SARS-COV-2 infection: in silco and in vitro studies.

Mamm Genome 2021 Jun 4. Epub 2021 Jun 4.

Cholistan University of Veterinary and Animal Sciences, Bahawalpur, 63100, Pakistan.

Acute Kidney Injury (AKI) is a common manifestation of COVID-19 and several cases have been reported in the setting of the high-risk APOL1 genotype (common genetic variants). This increases the likelihood that African American people with the high-risk genotype APOL1 are at increased risk for kidney disease in the COVID-19 environment. Single-nucleotide polymorphisms (SNPs) are found in various microRNAs (miRNAs) and target genes change the miRNA activity that leads to different diseases. Read More

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Exome sequencing reveals variants in known and novel candidate genes for severe sperm motility disorders.

Hum Reprod 2021 Jun 5. Epub 2021 Jun 5.

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

Study Question: What are the causative genetic variants in patients with male infertility due to severe sperm motility disorders?

Summary Answer: We identified high confidence disease-causing variants in multiple genes previously associated with severe sperm motility disorders in 10 out of 21 patients (48%) and variants in novel candidate genes in seven additional patients (33%).

What Is Known Already: Severe sperm motility disorders are a form of male infertility characterised by immotile sperm often in combination with a spectrum of structural abnormalities of the sperm flagellum that do not affect viability. Currently, depending on the clinical sub-categorisation, up to 50% of causality in patients with severe sperm motility disorders can be explained by pathogenic variants in at least 22 genes. Read More

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Individual culture leads to decreased blastocyst formation but does not affect pregnancy outcomes in the setting of a single, vitrified-warmed euploid blastocyst transfer.

J Assist Reprod Genet 2021 Jun 4. Epub 2021 Jun 4.

IVI-Reproductive Medicine Associates of New Jersey, Basking Ridge, NJ, USA.

Purpose: To evaluate embryology and pregnancy outcomes following individual and group embryo culture in the setting of contemporary laboratory practices and freeze-all cycles.

Methods: Patients underwent ovarian stimulation followed by intracytoplasmic sperm injection (ICSI). Embryos proceeded through individual culture and then underwent preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy. Read More

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Concordance of DNA Repair Gene Mutations in Paired Primary Prostate Cancer Samples and Metastatic Tissue or Cell-Free DNA.

JAMA Oncol 2021 Jun 4. Epub 2021 Jun 4.

Division of Oncology, Department of Medicine, University of Washington, Seattle.

Importance: DNA damage repair (DDR) gene mutations represent actionable alterations that can guide precision medicine strategies for advanced prostate cancer. However, acquisition of contemporary tissue samples for molecular testing can be a barrier to deploying precision medicine approaches. We hypothesized that most DDR alterations represent truncal events in prostate cancer and that primary tissue would faithfully reflect mutations found in cell-free circulating tumor DNA (ctDNA) and/or metastatic tissue. Read More

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Angiotensin-converting enzyme-1 gene insertion/deletion polymorphism may be associated with COVID-19 clinical severity: a prospective cohort study.

Ann Saudi Med 2021 May-Jun;41(3):141-146. Epub 2021 Jun 1.

From the Department of Internal Medicine, Section of Rheumatology, Samsun Education and Research Hospital, Samsun, Turkey.

Background: Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism may play a role in the pathogenesis of coronavirus-19 disease (COVID-19).

Objectives: Investigate the relationship between ACE I/D polymorphism and the clinical severity of COVID-19.

Design: Prospective cohort study. Read More

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Long-term outcomes of bariatric surgery in patients with bi-allelic mutations in the POMC, LEPR, and MC4R genes.

Surg Obes Relat Dis 2021 May 8. Epub 2021 May 8.

Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, CRNH Ile de France, F-CRIN/FORCE Network Paris, Paris, France; Sorbonne Université, INSERM, Nutrition and Obesities: Systemic Approaches (NutriOmics) Research Unit, F-CRIN/FORCE Network Paris, Paris, France.

Background: Gene mutations in the leptin-melanocortin signaling cascade lead to hyperphagia and severe early onset obesity. In most cases, multimodal conservative treatment (increased physical activity, reduced caloric intake) is not successful to stabilize body weight and control hyperphagia.

Objectives: To examine bariatric surgery as a therapeutic option for patients with genetic obesity. Read More

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Multitrait transcriptome-wide association study (TWAS) tests.

Genet Epidemiol 2021 Jun 3. Epub 2021 Jun 3.

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Multitrait tests can improve power to detect associations between individual single-nucleotide polymorphisms (SNPs) and several related traits. Here, we develop methods for multi-SNP transcriptome-wide association (TWAS) tests to test the association between predicted gene expression levels and multiple phenotypes. We show that the correlation in TWAS test statistics for multiple phenotypes has the same form as multitrait statistics for the single-SNP setting. Read More

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Monitoring of hospital sewage shows both promise and limitations as an early-warning system for carbapenemase-producing Enterobacterales in a low-prevalence setting.

Water Res 2021 May 17;200:117261. Epub 2021 May 17.

Centre for Antibiotic Resistance Research (CARe) at University of Gothenburg, Gothenburg, Sweden; Institute of Biomedicine, Department of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.

Carbapenemase-producing Enterobacterales (CPE) constitute a significant threat to healthcare systems. Continuous surveillance is important for the management and early warning of these bacteria. Sewage monitoring has been suggested as a possible resource-efficient complement to traditional clinical surveillance. Read More

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