78,268 results match your criteria gene carriers


Coding and Noncoding Variation in LRRK2 and Parkinson's Disease Risk.

Mov Disord 2021 Sep 20. Epub 2021 Sep 20.

Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.

Background: The leucine-rich repeat kinase 2 (LRRK2) gene harbors both rare highly damaging missense variants (eg, p.G2019S) and common noncoding variants (eg, rs76904798) with lower effect sizes that are associated with Parkinson's disease (PD) risk.

Objectives: This study aimed to investigate in a large meta-analysis whether the LRRK2 Genome-Wide Association Study (GWAS) signal represented by rs76904798 is independently associated with PD risk from LRRK2 coding variation and whether complex linkage disequilibrium structures with p. Read More

View Article and Full-Text PDF
September 2021

A genome-first approach to rare variants in hypertrophic cardiomyopathy genes MYBPC3 and MYH7 in a medical biobank.

Hum Mol Genet 2021 Sep 20. Epub 2021 Sep 20.

Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

'Genome-first' approaches to analyzing rare variants can reveal new insights into human biology and disease. Because pathogenic variants are often rare, new discovery requires aggregating rare coding variants into 'gene burdens' for sufficient power. However, a major challenge is deciding which variants to include in gene burden tests. Read More

View Article and Full-Text PDF
September 2021

Relationship between functional Nrf2 gene promoter polymorphism and sperm DNA damage in male infertility.

Syst Biol Reprod Med 2021 Sep 19:1-14. Epub 2021 Sep 19.

Department of Urology, School of Medicine, Ankara University, Ankara, Turkey.

This study examines the association of the -617 C > A polymorphism in the Nrf2 gene (rs6721961) with male infertility in a Turkish population and determines its functional role in spermatogenesis in correlation with the impact of different levels of DNA damage on the genotypes. A total of 100 infertile men and 100 healthy fertile men were included in the study. Nrf2 genotyping was performed with the PCR-based restriction fragment length gene polymorphism (RFLP-PCR) analysis. Read More

View Article and Full-Text PDF
September 2021

Allele-specific assembly of a eukaryotic genome corrects apparent frameshifts and reveals a lack of nonsense-mediated mRNA decay.

NAR Genom Bioinform 2021 Sep 16;3(3):lqab082. Epub 2021 Sep 16.

Division of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität in Munich, Lena-Christ-Str. 48, Planegg-Martinsried 82152, Germany.

To date, most reference genomes represent a mosaic consensus sequence in which the homologous chromosomes are collapsed into one sequence. This approach produces sequence artefacts and impedes analyses of allele-specific mechanisms. Here, we report an allele-specific genome assembly of the diploid parasite and reveal allelic variants affecting gene expression. Read More

View Article and Full-Text PDF
September 2021

The genetics of cardiac failure: Role of a G protein-coupled receptor polymorphism in therapeutic response in an Indian population.

J Clin Transl Res 2021 Aug 30;7(4):501-510. Epub 2021 Jul 30.

PSG Center for Molecular Medicine and Therapeutics, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India.

Background And Aim: The incidence of heart failure (HF) is rising to epidemic proportions in developing countries like India. A lack of adequate Indian studies underscores the importance of pursuing research into HF in an Indian population. G protein-coupled receptor kinase 5 ( Gln41>Leu (rs2230345) polymorphism was reported as a genetic modifier associated with survival in HF patients. Read More

View Article and Full-Text PDF

Risk of dementia in ε4 carriers is mitigated by a polygenic risk score.

Alzheimers Dement (Amst) 2021 14;13(1):e12229. Epub 2021 Sep 14.

Alzheimer Center Amsterdam Department of Neurology Amsterdam Neuroscience Vrije Universiteit Amsterdam Amsterdam UMC Amsterdam the Netherlands.

Introduction: We investigated relationships among genetic determinants of Alzheimer's disease (AD), amyloid/tau/neurodegenaration (ATN) biomarkers, and risk of dementia.

Methods: We studied cognitively normal individuals with subjective cognitive decline (SCD) from the Amsterdam Dementia Cohort and SCIENCe project. We examined associations between genetic variants and ATN biomarkers, and evaluated their predictive value for incident dementia. Read More

View Article and Full-Text PDF
September 2021

Quantitative Muscle MRI and Clinical Findings in Women With Pathogenic Dystrophin Gene Variants.

Front Neurol 2021 3;12:707837. Epub 2021 Sep 3.

Department of Neurology, Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

To explore fat replacement, muscle strength, and clinical features in women heterozygous for a pathogenic variant, we prospectively examined 53 women, assuming that some of these women-despite of the recessive X-linked inheritance-manifested clinical symptoms. We performed a cross-sectional observational study using MRI and stationary dynamometry of lower extremities, extracted blood muscle biomarkers, and investigated subjective complaints. Results were compared with 19 healthy women. Read More

View Article and Full-Text PDF
September 2021

Effects of Four Lipid Metabolism-Related Polymorphisms on Body Composition Improvements After 12 Weeks of High-Intensity Interval Training and Dietary Energy Restriction in Overweight/Obese Adult Women: A Pilot Study.

Front Physiol 2021 1;12:712787. Epub 2021 Sep 1.

Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile.

Polymorphisms in lipid metabolism-related genes have been associated with obesity and body composition, but these have been scarcely described concerning the magnitude of the response to exercise interventions in the overweight/obese population. To evaluate the association of perilipin 1 (; rs1052700 and rs2304795), lipoprotein lipase (rs283), and adrenoceptor beta 3 (rs4994) polymorphisms with high and low responders (LoRes) to fat mass reduction after 12 weeks of high-intensity interval training (HIIT) and dietary energy restriction in overweight/obese adult women. In addition, we examined the effect of these genetic variants on body composition changes. Read More

View Article and Full-Text PDF
September 2021

Neurofilament Light Chain and Intermediate HTT Alleles as Combined Biomarkers in Italian ALS Patients.

Front Neurosci 2021 3;15:695049. Epub 2021 Sep 3.

NEUROFARBA Department, University of Florence, Florence, Italy.

Objective: To study the possible implication of the two biomarkers, intermediate alleles (IAs) of the Huntingtin (HTT) gene and neurofilament light chain (NfL) levels in plasma, in amyotrophic lateral sclerosis (ALS) patients.

Methods: We analyzed IAs in a cohort of 106 Italian ALS patients and measured the plasma NfL levels in 20% of the patients of the cohort. We correlated the two biomarkers with clinical phenotypes. Read More

View Article and Full-Text PDF
September 2021

Investigating RFC1 expansions in sporadic amyotrophic lateral sclerosis.

J Neurol Sci 2021 Aug 31;430:118061. Epub 2021 Aug 31.

Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA; Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK; Neurology Department, Johns Hopkins University, Baltimore, MD 21205, USA.

A homozygous AAGGG repeat expansion within the RFC1 gene was recently described as a common cause of CANVAS syndrome. We examined 1069 sporadic ALS patients for the presence of this repeat expansion. We did not discover any carriers of the homozygous AAGGG expansion in our ALS cohort, indicating that this form of RFC1 repeat expansions is not a common cause of sporadic ALS. Read More

View Article and Full-Text PDF

Age of Onset of Huntington's Disease in Carriers of Reduced Penetrance Alleles.

Mov Disord 2021 Sep 18. Epub 2021 Sep 18.

Department of Psychiatry, Columbia University Medical Center, New York, New York, USA.

Background: Age of manifest Huntington's disease (HD) onset correlates with number of CAG repeats in the huntingtin gene. Little is known about onset with 36 to 39 repeats, the "reduced penetrance" (RP) range.

Objectives: We provide allele-specific estimates of HD penetrance (diagnostic confidence level of 4) for RP allele carriers. Read More

View Article and Full-Text PDF
September 2021

The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya.

Malar J 2021 Sep 17;20(1):371. Epub 2021 Sep 17.

Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.

Background: Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission.

Methods: In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa-Kipsamoite), asymptomatic P. Read More

View Article and Full-Text PDF
September 2021

Association between pathogenic germline mutations in BRCA2 and ATM and tumor-infiltrating lymphocytes in primary prostate cancer.

Cancer Immunol Immunother 2021 Sep 17. Epub 2021 Sep 17.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Pathogenic mutations in homologous recombination (HR) DNA repair genes may be associated with increased tumor mutational burden and numbers of tumor-infiltrating lymphocytes (TIL). Though HR-deficient prostate tumors have been anecdotally associated with improved responses to immunotherapy, it is unclear whether HR mutations or HR deficiency (HRD) scores predict for increased T-cell densities in this cancer. We evaluated 17 primary prostate tumors from patients with pathogenic germline BRCA2 mutations (gBRCA2) and 21 primary prostate tumors from patients with pathogenic germline ATM (gATM) mutations, which were compared to 19 control tumors lacking HR gene mutations, as well as the TCGA prostate cancer cohort. Read More

View Article and Full-Text PDF
September 2021

Macrophage migration inhibitory factor gene polymorphisms (SNP -173 G>C and STR-794 CATT5-8) confer risk of plaque psoriasis: A case-control study.

J Clin Lab Anal 2021 Sep 17:e23999. Epub 2021 Sep 17.

Centro de Investigación en Inmunología y Dermatología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.

Background: Macrophage inhibitory factor (MIF) is a pro-inflammatory cytokine secreted by several cells, including those in the immune system and the skin. The MIF gene contains the SNP -173 G> C and STR -794 CATT polymorphisms in the promoter region capable of affecting its activity. Our objective was to investigate the MIF polymorphisms as a risk factor for plaque psoriasis (PP) in the Mexican population. Read More

View Article and Full-Text PDF
September 2021

Early-Onset Cerebral Amyloid Angiopathy and Alzheimer Disease Related to an APP Locus Triplication.

Neurol Genet 2021 Oct 8;7(5):e609. Epub 2021 Sep 8.

Department of Neurology and CNR-MAJ (L.G., D.W.), Normandie University, UNIROUEN, Inserm U1245, CHU Rouen, CIC-CRB1404, F 76000; Department of Genetics and CNR-MAJ (K.C., S.R., N.L.M., A.R.-L., D.C., G.N.), Normandie University, UNIROUEN, Inserm U1245 and CHU Rouen, F 76000; Department of Neurology (B.C., M.F.), Lyon University Hospital; Department of Neurology (O.M.), Grenoble University Hospital; Department of Histology (J.B.), Grenoble University Hospital; AP-HP (M.M., T.C., E.T.-L.), Groupe Hospitalier Saint-Louis Lariboisière-Fernand-Widal, Service de Génétique Moléculaire Neurovasculaire, INSERM UMR 1141, NeuroDiderot,Université de Paris; Department of Histology Embryology and Cytogenetics (E.P.), Jean Verdier Hospital; Paris 13 University (E.P.), Sorbonne Paris Cité, UFR SMBH Bobigny; and PROTECT (E.P.), INSERM, Paris Diderot University, Bondy, France.

Background And Objective: To report a triplication of the amyloid-β precursor protein () locus along with relative messenger RNA (mRNA) expression in a family with autosomal dominant early-onset cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD).

Methods: Four copies of the gene were identified by quantitative multiplex PCR of short fluorescent fragments, fluorescent in situ hybridization (FISH), and array comparative genomic hybridization. mRNA levels were assessed using reverse-transcription-digital droplet PCR in the proband's whole blood and compared with 10 controls and 9 duplication carriers. Read More

View Article and Full-Text PDF
October 2021

Construction of a Novel Gene-Based Model for Survival Prediction of Hepatitis B Virus Carriers With HCC Development.

Front Genet 2021 31;12:720888. Epub 2021 Aug 31.

Department of Biochemistry and Molecular Biology, School of Bioscience and Technology, Chengdu Medical College, Chengdu, China.

Despite the effectiveness of hepatitis B virus (HBV) vaccination in reducing the prevalence of chronic HBV infection as well as the incidence of acute hepatitis B, fulminant hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC), there was still a large crowd of chronically infected populations at risk of developing cirrhosis or HCC. In this study, we established a comprehensive prognostic system covering multiple signatures to elevate the predictive accuracy for overall survival (OS) of hepatitis B virus carriers with HCC development. Weighted Gene Co-Expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine Recursive Feature Elimination (SVM-RFE), and multivariate COX analysis, along with a suite of other online analyses were successfully applied to filtrate a three-gene signature model (, , and ). Read More

View Article and Full-Text PDF

Clinical and molecular characterization of patients fulfilling Chompret criteria for Li-Fraumeni syndrome in Southern Brazil.

PLoS One 2021 16;16(9):e0251639. Epub 2021 Sep 16.

Programa de Pós-Graduação em Genética e Biologia Molecular (PPGBM), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome caused by pathogenic germline variants in the TP53 gene, characterized by a predisposition to the development of a broad spectrum of tumors at an early age. The core tumors related to LFS are bone and soft tissue sarcomas, premenopausal breast cancer, brain tumors, adrenocortical carcinomas (ACC), and leukemias. The revised Chompret criteria has been widely used to establish clinical suspicion and support TP53 germline variant testing and LFS diagnosis. Read More

View Article and Full-Text PDF
September 2021

Genetic testing in women with early-onset breast cancer: a Traceback pilot study.

Breast Cancer Res Treat 2021 Sep 16. Epub 2021 Sep 16.

Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.

Purpose: In Sweden, a Traceback approach, i.e., a retrospective genetic outreach activity, among cancer patients is not normally used in clinical practice. Read More

View Article and Full-Text PDF
September 2021

Risk of Pancreatic Cancer Among Individuals With Pathogenic Variants in the ATM Gene.

JAMA Oncol 2021 Sep 16. Epub 2021 Sep 16.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.

Importance: Pathogenic germline variants in the ATM gene have been associated with pancreatic cancer risk. Although genetic testing identifies these variants in approximately 1% to 3% of unselected patients with pancreatic cancer, the lifetime risk of pancreatic cancer among individuals with pathogenic ATM variants has not been well estimated.

Objective: To estimate age-specific penetrance of pancreatic cancer in individuals with a pathogenic variant in the ATM gene. Read More

View Article and Full-Text PDF
September 2021

CircRNA: A novel potential strategy to treat thyroid cancer (Review).

Int J Mol Med 2021 Nov 16;48(5). Epub 2021 Sep 16.

Endocrinology Department, The First Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.

Thyroid cancer (TC) is the most common type of endocrine cancer. Over the last 50 years, the global incidence of TC has been increasing. The survival rate of TC is higher than that of most other types of cancer, but it depends on numerous factors, including the specific type of TC and stage of the disease. Read More

View Article and Full-Text PDF
November 2021

Interlukin-27 rs153109 polymorphism confers the susceptibility and prognosis of aplastic anemia in Chinese population.

Authors:
Wei Yu Wu Yang

Int J Lab Hematol 2021 Sep 15. Epub 2021 Sep 15.

Department of International Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.

Introduction: Accumulating evidence has indicated that interleukin (IL)-27 and its gene polymorphisms exert pivotal impact on several autoimmune disorders. This research intended to investigate the relationship between IL-27 rs153109 polymorphism with risk and prognosis for aplastic anemia.

Methods: IL-27 rs153109 polymorphism was detected with polymerase chain reaction-ligase detection reaction in 238 patients with aplastic anemia and 215 normal individuals. Read More

View Article and Full-Text PDF
September 2021

Comparisons of +3179G/A insulin-like growth factor 1 receptor gene distribution between two inflammatory arthritides and healthy adults.

Arch Rheumatol 2021 Jun 14;36(2):227-232. Epub 2021 Jan 14.

Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Stara Zagora, Bulgaria.

Objectives: This study aims to investigate whether single nucleotide polymorphisms (SNPs) at the +3179G/A insulin-like growth factor 1 receptor (IGF-1R) locus were associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) genetic susceptibility and also explore age and sex distribution of the rs2229765 in healthy adults.

Patients And Methods: This cross-sectional study was conducted between September 2012 and October 2014. Seventy patients with RA (7 males, 63 females; mean age: 54±1 years; range, 32 to 78 years) and 56 with AS (44 males, 12 females; mean age: 38±9 years; range, 22 to 57 years) were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Read More

View Article and Full-Text PDF

Baculoviral inhibitor of apoptosis family of proteins repeat-containing 5 gene methylation status in peripheral blood mononuclear cells and plasma survivin levels in patients with Behçet's disease.

Arch Rheumatol 2021 Jun 14;36(2):185-191. Epub 2021 Jan 14.

Department of Internal Medicine, Connective Tissue Diseases Research Center, Tabriz, Iran.

Objectives: This study aims to evaluate the baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene methylation in the peripheral blood mononuclear cells (PBMCs) in patients with Behçet's disease (BD) compared to healthy controls and the association of survivin with BD activity.

Patients And Methods: A cross-sectional study was conducted on 43 BD patients (22 males, 21 females; mean age 36.6±10. Read More

View Article and Full-Text PDF

Identification of a novel mutation in with functional analysis in a cohort of 516 familial patients with exudative vitreoretinopathy.

Mol Vis 2021 1;27:528-541. Epub 2021 Sep 1.

Department of Ophthalmology, Xinhua Hospital, Affiliated to Medicine School of Shanghai Jiaotong University, No. 1665, Kongjiang Road, Shanghai, China.

Purpose: To identify a novel mutation in with clinical and functional analysis among 516 familial patients with exudative vitreoretinopathy (FEVR).

Methods: Next-generation sequencing was performed on 516 patients with FEVR between January 2015 and October 2017. Clinical data were collected from patient charts, including sex, age at presentation, visual acuity if available, axial length, stage, and systemic clinical findings. Read More

View Article and Full-Text PDF
September 2021

Extended spectrum beta-lactamase-producing Escherichia coli from extraintestinal infections in humans and from food-producing animals, in Italy: a "One Health" study.

Int J Antimicrob Agents 2021 Sep 12:106433. Epub 2021 Sep 12.

Istituto Superiore di Sanità, Rome, Italy; Department of Medicine-University of Udine and Clinical Risk Management and Performance Assessment Unit, Udine Healthcare and University Integrated Trust, Udine, Italy.

In recent years, Escherichia coli producing extended spectrum beta-lactamases (ESBL) have become a serious public health problem and food-producing animals (FPA) have been suggested as a potential reservoir/source. In this study, we aimed to compare ESBL-producing E. coli isolates from different sources. Read More

View Article and Full-Text PDF
September 2021

A natural variant in ANP32B impairs influenza virus replication in human cells.

J Gen Virol 2021 Sep;102(9)

Department of Infectious Disease, Faculty of Medicine, Imperial College London, UK.

Viruses require host factors to support their replication, and genetic variation in such factors can affect susceptibility to infectious disease. Influenza virus replication in human cells relies on ANP32 proteins, which are involved in assembly of replication-competent dimeric influenza virus polymerase (FluPol) complexes. Here, we investigate naturally occurring single nucleotide variants (SNV) in the human and genes. Read More

View Article and Full-Text PDF
September 2021

Direct PCR assays without DNA extraction for rapid detection of hemoglobin Constant Spring and Pakse' genes: application for carrier screening and prenatal diagnosis.

Scand J Clin Lab Invest 2021 Sep 15:1-7. Epub 2021 Sep 15.

Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.

Hemoglobin Constant Spring (Hb CS) and Hb Pakse' (PS) are the common non-deletional α-thalassemia found in Thailand. These two variants can cause severe thalassemia syndromes, especially in fetus and neonate. Molecular diagnosis is the only confirmatory method because Hb CS and Hb PS are usually missed by routine screening and Hb analysis. Read More

View Article and Full-Text PDF
September 2021

Aspects of the Neurospora crassa Sulfur Starvation Response Are Revealed by Transcriptional Profiling and DNA Affinity Purification Sequencing.

mSphere 2021 Sep 15:e0056421. Epub 2021 Sep 15.

Plant and Microbial Biology Department, University of California, Berkeleygrid.47840.3f, California, USA.

Accurate nutrient sensing is important for rapid fungal growth and exploitation of available resources. Sulfur is an important nutrient source found in a number of biological macromolecules, including proteins and lipids. The model filamentous fungus Neurospora crassa is capable of utilizing sulfur found in a variety of sources from amino acids to sulfate. Read More

View Article and Full-Text PDF
September 2021

Reviewing pharmacogenetics to advance precision medicine for opioids.

Biomed Pharmacother 2021 Sep 12;142:112060. Epub 2021 Sep 12.

Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Institute of Medical Sciences, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Centre for Addiction and Mental Health, Toronto, ON, Canada. Electronic address:

Background: Adequate opioid prescribing is critical for therapeutic success of pain management. Despite the widespread use of opioids, optimized opioid therapy remains unresolved with risk of accidental lethal overdosing. With the emergence of accumulating evidence linking genetic variation to opioid response, pharmacogenetic based treatment recommendations have been proposed. Read More

View Article and Full-Text PDF
September 2021

Effects of Ocufolin on retinal microvasculature in patients with mild non-proliferative diabetic retinopathy carrying polymorphisms of the MTHFR gene.

BMJ Open Diabetes Res Care 2021 Sep;9(1)

Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, USA

Introduction: To evaluate effects of Ocufolin on retinal microvasculature in mild non-proliferative diabetic retinopathy patients who carried methylenetetrahydrofolate reductase (MTHFR) polymorphisms (DR+MTHFRP).

Research Design And Methods: This is a prospective cohort study. Eight DR+MTHFRP (administrated Ocufolin for 6 months) and 15 normal controls (NCs) were recruited. Read More

View Article and Full-Text PDF
September 2021