keyword
MENU ▼
Read by QxMD icon Read
search

Heritable disorders

keyword
https://www.readbyqxmd.com/read/27911742/current-perspectives-in-autism-spectrum-disorder-from-genes-to-therapy
#1
Maria Chahrour, Brian J O'Roak, Emanuela Santini, Rodney C Samaco, Robin J Kleiman, M Chiara Manzini
Autism spectrum disorder (ASD) is a constellation of neurodevelopmental presentations with high heritability and both phenotypic and genetic heterogeneity. To date, mutations in hundreds of genes have been associated to varying degrees with increased ASD risk. A better understanding of the functions of these genes and whether they fit together in functional groups or impact similar neuronal circuits is needed to develop rational treatment strategies. We will review current areas of emphasis in ASD research, starting from human genetics and exploring how mouse models of human mutations have helped identify specific molecular pathways (protein synthesis and degradation, chromatin remodeling, intracellular signaling), which are linked to alterations in circuit function and cognitive/social behavior...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27898412/the-rise-and-rise-of-exome-sequencing
#2
Chee-Seng Ku, David N Cooper, George P Patrinos
Beginning in 2009, the advent of exome sequencing has contributed significantly towards new discoveries of heritable germline mutations and de novo mutations for rare Mendelian disorders with hitherto unknown genetic aetiologies. Exome sequencing is an efficient tool to identify disease mutations without the need of a multi-generational pedigree. Sequencing a single proband or multiple affected individuals has been shown to be successful in identifying disease mutations, but parents would be required in the case of de novo mutations...
November 30, 2016: Public Health Genomics
https://www.readbyqxmd.com/read/27893734/an-ipsc-derived-vascular-model-of-marfan-syndrome-identifies-key-mediators-of-smooth-muscle-cell-death
#3
Alessandra Granata, Felipe Serrano, William George Bernard, Madeline McNamara, Lucinda Low, Priya Sastry, Sanjay Sinha
Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in FBN1, which encodes the extracellular matrix protein fibrillin-1. To investigate the pathogenesis of aortic aneurysms in MFS, we generated a vascular model derived from human induced pluripotent stem cells (MFS-hiPSCs). Our MFS-hiPSC-derived smooth muscle cells (SMCs) recapitulated the pathology seen in Marfan aortas, including defects in fibrillin-1 accumulation, extracellular matrix degradation, transforming growth factor-β (TGF-β) signaling, contraction and apoptosis; abnormalities were corrected by CRISPR-based editing of the FBN1 mutation...
November 28, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27892595/the-rate-of-change-in-alcohol-misuse-across-adolescence-is-heritable
#4
Alexis C Edwards, Jon Heron, Vladimir Vladimirov, Aaron R Wolen, Daniel E Adkins, Fazil Aliev, Matthew Hickman, Kenneth S Kendler
BACKGROUND: Alcohol use typically begins during adolescence and escalates into young adulthood. This represents an important period for the establishment of alcohol use and misuse patterns, which can have psychosocial and medical consequences. Although changes in alcohol use during this time have been phenotypically characterized, their genetic nature is poorly understood. METHODS: Participants of the Avon Longitudinal Study of Parents and Children completed the Alcohol Use Disorders Identification Test (AUDIT) 4 times from age 16 to 20...
November 28, 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27891231/a-pharmacokinetic-evaluation-and-metabolite-identification-of-the-ghb-receptor-antagonist-ncs-382-in-mouse-informs-novel-therapeutic-strategies-for-the-treatment-of-ghb-intoxication
#5
Garrett R Ainslie, K Michael Gibson, Kara R Vogel
Gamma-aminobutyric acid (GABA) is an endogenous inhibitory neurotransmitter and precursor of gamma-hydroxybutyric acid (GHB). NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzo-cyclohept-6-ylideneacetic acid), a known GHB receptor antagonist, has shown significant efficacy in a murine model of succinic semialdehyde dehydrogenase deficiency (SSADHD), a heritable neurological disorder featuring chronic elevation of GHB that blocks the final step of GABA degradation. NCS-382 exposures and elimination pathways remain unknown; therefore, the goal of the present work was to obtain in vivo pharmacokinetic data in a murine model and to identify the NCS-382 metabolites formed by mouse and human...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/27890468/genetic-overlap-between-attention-deficit-hyperactivity-disorder-and-bipolar-disorder-evidence-from-genome-wide-association-study-meta-analysis
#6
Kimm J E van Hulzen, Claus J Scholz, Barbara Franke, Stephan Ripke, Marieke Klein, Andrew McQuillin, Edmund J Sonuga-Barke, John R Kelsoe, Mikael Landén, Ole A Andreassen, Klaus-Peter Lesch, Heike Weber, Stephen V Faraone, Alejandro Arias-Vasquez, Andreas Reif
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently co-occurring and highly heritable mental health conditions. We hypothesized that BPD cases with an early age of onset (≤21 years old) would be particularly likely to show genetic covariation with ADHD. METHODS: Genome-wide association study data were available for 4609 individuals with ADHD, 9650 individuals with BPD (5167 thereof with early-onset BPD), and 21,363 typically developing controls...
October 18, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27884859/isolated-gnrh-deficiency-genotypic-and-phenotypic-characteristics-of-the-genetically-heterogeneous-greek-population
#7
Maria I Stamou, Petros Varnavas, Machi Kentrou, Fotini Adamidou, Antonis Voutetakis, Jenny Jing, Lacey Plummer, Vasiliki Koika, Neoklis A Georgopoulos
OBJECTIVE: Isolated GnRH Deficiency (IGD) is a rare heritable disorder characterized by phenotypic and genetic heterogeneity. The genetic complexity of IGD has been surfaced by analyzing clinically complex cases, structural genetic variation as well as endogamous familial cases and isolated populations, revealing an enrichment for particular genes/ pathways that reflects the homogeneous genetic background of such populations. DESIGN AND METHODS: We analyzed a cohort of 81 Greek IGD patients by performing detailed phenotyping, followed by Sanger Sequencing of 14 causative IGD genes...
November 24, 2016: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27881557/plasma-metabolomics-implicate-modified-transfer-rnas-and-altered-bioenergetics-in-the-outcome-of-pulmonary-arterial-hypertension
#8
Christopher J Rhodes, Pavandeep Ghataorhe, John Wharton, Kevin C Rue-Albrecht, Charaka Hadinnapola, Geoffrey Watson, Marta Bleda, Matthias Haimel, Gerry Coghlan, Paul A Corris, Luke S Howard, David G Kiely, Andrew J Peacock, Joanna Pepke-Zaba, Mark Toshner, Stephen J Wort, J Simon R Gibbs, Allan Lawrie, Stefan Gräf, Nicholas W Morrell, Martin R Wilkins
BACKGROUND: -Pulmonary arterial hypertension (PAH) is a heterogeneous disorder with high mortality. METHODS: -We conducted a comprehensive study of plasma metabolites using ultra-performance liquid chromatography mass-spectrometry to (1) identify patients at high risk of early death, (2) identify patients who respond well to treatment and (3) provide novel molecular insights into disease pathogenesis. RESULTS: -53 circulating metabolites distinguished well-phenotyped patients with idiopathic or heritable PAH (n=365) from healthy controls (n=121) following correction for multiple testing (p<7...
November 21, 2016: Circulation
https://www.readbyqxmd.com/read/27880996/oxidative-stress-induced-damage-to-paternal-genome-and-impact-of-meditation-and-yoga-can-it-reduce-incidence-of-childhood-cancer
#9
Dada Rima, Basant Kumar Shiv, Chawla Bhavna, Bisht Shilpa, Khan Saima
Background: Sperm DNA damage is underlying aetiology of poor implantation and pregnancy rates but also affects health of offspring and may also result in denovo mutations in germ line and post fertilization. This may result in complex diseases, polygenic disorders and childhood cancers. Childhood cancer like retinoblastoma (RB) is more prevalent in developing countries and the incidence of RB has increased more than three fold in India in the last decade. Recent studies have documented increased incidence of cancers in children born to fathers who consume alcohol in excess and tobacco or who were conceived by assisted conception...
January 9, 2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27876814/a-genome-wide-investigation-into-parent-of-origin-effects-in-autism-spectrum-disorder-identifies-previously-associated-genes-including-shank3
#10
Siobhan Connolly, Richard Anney, Louise Gallagher, Elizabeth A Heron
Autism spectrum disorder (ASD) is known to be a heritable neurodevelopmental disorder affecting more than 1% of the population but in the majority of ASD cases, the genetic cause has not been identified. Parent-of-origin effects have been highlighted as an important mechanism in the pathology of neurodevelopmental disorders such as Prader-Willi and Angelman syndrome, with individuals with these syndromes often exhibiting ASD symptoms. Consequently, systematic investigation of these effects in ASD is clearly an important line of investigation in elucidating the underlying genetic mechanisms...
November 23, 2016: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/27876231/paternal-preconception-alcohol-exposure-imparts-intergenerational-alcohol-related-behaviors-to-male-offspring-on-a-pure-c57bl-6j-background
#11
Gregory R Rompala, Andrey Finegersh, Michelle Slater, Gregg E Homanics
While alcohol use disorder (AUD) is a highly heritable condition, the basis of AUD in families with a history of alcoholism is difficult to explain by genetic variation alone. Emerging evidence suggests that parental experience prior to conception can impact inheritance of complex behaviors in offspring via non-genomic (epigenetic) mechanisms. For instance, male C57BL/6J (B6) mice exposed to chronic intermittent vapor ethanol (CIE) prior to mating with Strain 129S1/SvImJ ethanol-naïve females produce male offspring with reduced ethanol drinking preference, increased ethanol sensitivity, and increased BDNF expression in the ventral tegmental area (VTA)...
November 5, 2016: Alcohol
https://www.readbyqxmd.com/read/27872268/consistent-functional-connectivity-alterations-in-schizophrenia-spectrum-disorder-a-multisite-study
#12
Kristina C Skåtun, Tobias Kaufmann, Nhat Trung Doan, Dag Alnæs, Aldo Córdova-Palomera, Erik G Jönsson, Helena Fatouros-Bergman, Lena Flyckt, Ingrid Melle, Ole A Andreassen, Ingrid Agartz, Lars T Westlye
Schizophrenia (SZ) is a severe mental illness with high heritability and complex etiology. Mounting evidence from neuroimaging has implicated disrupted brain network connectivity in the pathophysiology. However, previous findings are inconsistent, likely due to a combination of methodological and clinical variability and relatively small sample sizes. Few studies have used a data-driven approach for characterizing pathological interactions between regions in the whole brain and evaluated the generalizability across independent samples...
November 21, 2016: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/27872260/familial-aggregation-and-heritability-of-schizophrenia-and-co-aggregation-of-psychiatric-illnesses-in-affected-families
#13
I-Jun Chou, Chang-Fu Kuo, Yu-Shu Huang, Matthew J Grainge, Ana M Valdes, Lai-Chu See, Kuang-Hui Yu, Shue-Fen Luo, Lu-Shuang Huang, Wen-Yi Tseng, Weiya Zhang, Michael Doherty
Strong familial aggregation of schizophrenia has been reported but there is uncertainty concerning the degree of genetic contribution to the phenotypic variance of the disease. This study aimed to examine the familial aggregation and heritability of schizophrenia, and the relative risks (RRs) of other psychiatric diseases, in relatives of people with schizophrenia using the Taiwan National Health Insurance Database. The study population included individuals with affected first-degree or second-degree relatives identified from all beneficiaries (n = 23 422 955) registered in 2013...
November 21, 2016: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/27872008/the-genetic-basis-of-peyronie-disease-a-review
#14
REVIEW
Amin S Herati, Alexander W Pastuszak
INTRODUCTION: Peyronie disease (PD) is a progressive fibrotic disorder of the penile tunica albuginea that results in fibrotic penile plaques and can lead to penile deformity. Characterized by aberrant fibrosis resulting in part from the persistence of myofibroblasts and altered gene expression, the molecular factors underpinning PD and other related fibrotic diatheses are just being elucidated. A genetic link to PD was first identified three decades ago using pedigree analyses. However, the specific genetic factors that predispose patients to aberrant fibrosis remain unknown, and the relations between these fibrotic conditions and other heritable diseases, including malignancy, are uncharacterized...
January 2016: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/27871638/single-nucleotide-polymorphism-heritability-of-a-general-psychopathology-factor-in-children
#15
Alexander Neumann, Irene Pappa, Benjamin B Lahey, Frank C Verhulst, Carolina Medina-Gomez, Vincent W Jaddoe, Marian J Bakermans-Kranenburg, Terrie E Moffitt, Marinus H van IJzendoorn, Henning Tiemeier
OBJECTIVE: Co-occurrence of mental disorders is commonly observed, but the etiology underlying this observation is poorly understood. Studies in adolescents and adults have identified a general psychopathology factor associated with a high risk for different psychiatric disorders. We defined a multi-informant general psychopathology factor in school-aged children and estimated its single nucleotide polymorphism (SNP) heritability. The goal was to test the hypothesis that child behavioral and emotional problems are under the influence of highly pleiotropic common autosomal genetic variants that nonspecifically increase the risk for different dimensions of psychopathology...
December 2016: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/27870456/understanding-the-epigenetic-basis-of-sex-differences-in-depression
#16
REVIEW
Georgia E Hodes, Deena M Walker, Benoit Labonté, Eric J Nestler, Scott J Russo
Epigenetics refers to potentially heritable processes that can mediate both lasting and transient changes in gene expression in the absence of genome sequence alterations. The field of epigenetics has introduced a novel understanding of the mechanisms through which the environment can shape an individual and potentially its offspring. This Mini-Review examines the current literature exploring the role of epigenetics in the development of mood disorders such as depression. Depression is twofold more common in females, yet the majority of preclinical research has been conducted exclusively in male subjects...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27864587/evaluation-of-the-genetic-basis-of-primary-hypoadrenocorticism-in-standard-poodles-using-snp-array-genotyping-and-whole-genome-sequencing
#17
Steven G Friedenberg, Katharine F Lunn, Kathryn M Meurs
Primary hypoadrenocorticism, also known as Addison's disease, is an autoimmune disorder leading to the destruction of the adrenal cortex and subsequent loss of glucocorticoid and mineralocorticoid hormones. The disease is prevalent in Standard Poodles and is believed to be highly heritable in the breed. Using genotypes derived from the Illumina Canine HD SNP array, we performed a genome-wide association study of 133 carefully phenotyped Standard Poodles (61 affected, 72 unaffected) and found no markers significantly associated with the disease...
November 18, 2016: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/27864402/molecular-genetic-contributions-to-self-rated-health
#18
Sarah E Harris, Saskia P Hagenaars, Gail Davies, W David Hill, David C M Liewald, Stuart J Ritchie, Riccardo E Marioni, Cathie L M Sudlow, Joanna M Wardlaw, Andrew M McIntosh, Catharine R Gale, Ian J Deary
BACKGROUND: Poorer self-rated health (SRH) predicts worse health outcomes, even when adjusted for objective measures of disease at time of rating. Twin studies indicate SRH has a heritability of up to 60% and that its genetic architecture may overlap with that of personality and cognition. METHODS: We carried out a genome-wide association study (GWAS) of SRH on 111 749 members of the UK Biobank sample. Univariate genome-wide complex trait analysis (GCTA)-GREML analyses were used to estimate the proportion of variance explained by all common autosomal single nucleotide polymorphisms (SNPs) for SRH...
November 17, 2016: International Journal of Epidemiology
https://www.readbyqxmd.com/read/27861851/infant-social-attention-an-endophenotype-of-asd-related-traits
#19
Emily J H Jones, Kaitlin Venema, Rachel K Earl, Rachel Lowy, Sara J Webb
BACKGROUND: As a neurodevelopmental disorder, symptoms of ASD likely emerge from a complex interaction between preexisting genetic vulnerabilities and the child's environment. One way to understand causal paths to ASD is to identify dimensional ASD-related traits that vary in the general population and that predispose individuals with other risk factors toward ASD. Moving beyond behavioral traits to explore underlying neurocognitive processes may further constrain the underlying genetics...
November 8, 2016: Journal of Child Psychology and Psychiatry, and Allied Disciplines
https://www.readbyqxmd.com/read/27856950/the-role-of-epigenetics-in-social-psychiatry
#20
REVIEW
Jacob Peedicayil
BACKGROUND: Epigenetics refers to the study of heritable changes in gene expression not involving changes in DNA sequence and is presently an active area of research in biology and medicine. There is increasing evidence that epigenetics is involved in the pathogenesis of psychiatric disorders. AIMS AND METHODS: Several studies conducted to date have suggested that psychosocial factors act by modifying epigenetic mechanisms of gene expression in the brain in the pathogenesis of psychiatric disorders...
November 16, 2016: International Journal of Social Psychiatry
keyword
keyword
3788
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"