journal
MENU ▼
Read by QxMD icon Read
search

Human Molecular Genetics

journal
https://www.readbyqxmd.com/read/27794540/pink1-and-parkin-are-genetic-modifiers-for-fus-induced-neurodegeneration
#1
Yanbo Chen, Jianwen Deng, Peng Wang, Mengxue Yang, Xiaoping Chen, Li Zhu, Jianghong Liu, Bingwei Lu, Yan Shen, Kazuo Fushimi, Qi Xu, Jane Y Wu
Dysregulation of FUS gene expression is associated with fronto-temporal lobar degeneration (FTLD), and missense mutations in the FUS gene have been identified in patients affected by amyotrophic lateral sclerosis (ALS). However, molecular and cellular defects underlying FUS proteinopathy remain to be elucidated. Here, we examined whether genes important for mitochondrial quality control play a role in FUS proteinopathy. In our genetic screening, Pink1 and Park genes were identified as modifiers of neurodegeneration phenotypes induced by wild type (Wt) or ALS-associated P525L-mutant human FUS...
October 29, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27794539/human-r1441c-lrrk2-regulates-the-synaptic-vesicle-proteome-and-phosphoproteome-in-a-drosophila-model-of-parkinson-s-disease
#2
Shariful Islam, Hendrik Nolte, Wright Jacob, Anna B Ziegler, Stefanie Pütz, Yael Grosjean, Karolina Szczepanowska, Aleksandra Trifunovic, Thomas Braun, Hermann Heumann, Rolf Heumann, Bernhard Hovemann, Darren J Moore, Marcus Krüger
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset, autosomal dominant familial Parkinson's disease (PD) and variation at the LRRK2 locus contributes to the risk for idiopathic PD. LRRK2 can function as a protein kinase and mutations lead to increased kinase activity. To elucidate the pathophysiological mechanism of the R1441C mutation in the GTPase domain of LRRK2, we expressed human wild-type or R1441C LRRK2 in dopaminergic neurons of Drosophila and observe reduced locomotor activity, impaired survival and an age-dependent degeneration of dopaminergic neurons thereby creating a new PD-like model...
October 29, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798116/most-brain-disease-associated-and-eqtl-haplotypes-are-not-located-within-transcription-factor-dnase-seq-footprints-in-brain
#3
Adam E Handel, Giuseppe Gallone, M Zameel Cader, Chris P Ponting
Dense genotyping approaches have revealed much about the genetic architecture both of gene expression and disease susceptibility. However, assigning causality to genetic variants associated with a transcriptomic or phenotypic trait presents a far greater challenge. The development of epigenomic resources by ENCODE, the Epigenomic Roadmap and others has led to strategies that seek to infer the likely functional variants underlying these genome-wide association signals. It is known, for example, that such variants tend to be located within areas of open chromatin, as detected by techniques such as DNase-seq and FAIRE-seq...
October 26, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798115/lamina-associated-polypeptide-1-is-dispensable-for-embryonic-myogenesis-but-required-for-postnatal-skeletal-muscle-growth
#4
Ji-Yeon Shin, Iván Méndez-López, Mingi Hong, Yuexia Wang, Kurenai Tanji, Wei Wu, Leana Shugol, Robert S Krauss, William T Dauer, Howard J Worman
Lamina-associated polypeptide 1 (LAP1) is an integral protein of the inner nuclear membrane that has been implicated in striated muscle maintenance. Mutations in its gene have been linked to muscular dystrophy and cardiomyopathy. As germline deletion of the gene encoding LAP1 is perinatal lethal, we explored its potential role in myogenic differentiation and development by generating a conditional knockout mouse in which the protein is depleted from muscle progenitors at embryonic day 8.5 (Myf5-Lap1CKO mice)...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798114/systemic-aav9-gene-therapy-improves-the-lifespan-of-mice-with-niemann-pick-disease-type-c1
#5
Randy J Chandler, Ian M Williams, Alana L Gibson, Cristin D Davidson, Arturo A Incao, Brandon T Hubbard, Forbes D Porter, William J Pavan, Charles P Venditti
Niemann-Pick disease, type C1 (NPC1) is a heritable lysosomal storage disease characterized by a progressive neurological degeneration that causes disability and premature death. A murine model of NPC1 disease (Npc1(-/-)) displays a rapidly progressing form of NPC1 disease which is characterized by weight loss, ataxia, increased cholesterol storage, loss of cerebellar Purkinje neurons and early lethality. To test the potential efficacy of gene therapy for NPC1, we constructed adeno-associated virus serotype 9 (AAV9) vectors to deliver the NPC1 gene under the transcriptional control of the neuronal-specific (CamKII) or a ubiquitous (EF1a) promoter...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798113/oral-facial-digital-syndrome-type-i-cells-exhibit-impaired-dna-repair-unanticipated-consequences-of-defective-ofd1-outside-of-the-cilia-network
#6
Iga Abramowicz, Gillian Carpenter, Mariaevelina Alfieri, Rita Colnaghi, Emily Outwin, Philippe Parent, Christel Thauvin-Robinet, Daniela Iaconis, Brunella Franco, Mark O'Driscoll
Defects in OFD1 underlie the clinically complex ciliopathy, Oral-Facial-Digital syndrome Type I (OFD Type I). Our understanding of the molecular, cellular and clinical consequences of impaired OFD1 originate from its characterised roles at the centrosome/basal body/cilia network. Nonetheless, the first described OFD1 interactors were components of the TIP60 histone acetyltransferase complex. We find that OFD1 can also localise to chromatin and its reduced expression is associated with mis-localization of TIP60 in patient-derived cell lines...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798112/leucine-rich-repeat-kinase-2-exacerbates-neuronal-cytotoxicity-through-phosphorylation-of-histone-deacetylase3-and-histone-deacetylation
#7
Kyung Ah Han, Wongi Seol, Hyemyung Seo, CheMyong Ko, Kwang Chul Chung
Parkinson's disease (PD) is characterized by slow, progressive degeneration of dopaminergic neurons in the substantia nigra. The cause of neuronal death in PD is largely unknown, but several genetic loci, including leucine-rich repeat kinase 2 (LRRK2), have been identified. LRRK2 has guanosine triphosphatase (GTPase) and kinase activities, and mutations in LRRK2 are the major cause of autosomal-dominant familial PD. Histone deacetylases (HDACs) remove acetyl groups from lysine residues on histone tails, promoting transcriptional repression via condensation of chromatin...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798111/the-ring-finger-domain-e3-ubiquitin-ligases-brca1-and-the-rnf20-rnf40-complex-in-global-loss-of-the-chromatin-mark-histone-h2b-monoubiquitination-h2bub1-in-cell-line-models-and-primary-high-grade-serous-ovarian-cancer
#8
Kristie-Ann Dickson, Alexander J Cole, Anthony J Gill, Adele Clarkson, Gregory B Gard, Angela Chou, Catherine J Kennedy, Beric R Henderson, Sian Fereday, Nadia Traficante, Kathryn Alsop, David D Bowtell, Anna deFazio, Roderick Clifton-Bligh, Deborah J Marsh
Enzymatic factors driving cancer-associated chromatin remodelling are of increasing interest as the role of the cancer epigenome in gene expression and DNA repair processes becomes elucidated. Monoubiquitination of histone H2B at lysine 120 (H2Bub1) is a central histone modification that functions in histone cross-talk, transcriptional elongation, DNA repair, maintaining centromeric chromatin and replication-dependent histone mRNA 3'-end processing, as well as being required for the differentiation of stem cells...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798110/variegated-yet-non-random-rod-and-cone-photoreceptor-disease-patterns-in-rpgr-orf15-associated-retinal-degeneration
#9
Jason Charng, Artur V Cideciyan, Samuel G Jacobson, Alexander Sumaroka, Sharon B Schwartz, Malgorzata Swider, Alejandro J Roman, Rebecca Sheplock, Manisha Anand, Marc C Peden, Hemant Khanna, Elise Heon, Alan F Wright, Anand Swaroop
Mutations in the ORF15 exon of the RPGR gene cause a common form of X-linked retinitis pigmentosa, which often results in severe loss of vision. In dogs and mice, gene augmentation therapy has been shown to arrest the progressive degeneration of rod and cone photoreceptors. However, the distribution of potentially treatable photoreceptors across the human retinas and the rate of degeneration are not known. Here, we have defined structure and functional features of the disease in 70 individuals with ORF15 mutations...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798109/embryonic-forebrain-transcriptome-of-mice-with-polyalanine-expansion-mutations-in-the-arx-homeobox-gene
#10
Tessa Mattiske, Kristie Lee, Jozef Gecz, Gaelle Friocourt, Cheryl Shoubridge
The Aristaless related homeobox (ARX) gene encodes a paired-type homeodomain transcription factor with critical roles in embryonic development. Mutations in ARX give rise to intellectual disability (ID), epilepsy and brain malformation syndromes. To capture the genetics and molecular disruptions that underpin the ARX-associated clinical phenotypes, we undertook a transcriptome wide RNASeq approach to analyse developing (12.5 dpc) telencephalon of mice modelling two recurrent polyalanine expansion mutations with different phenotypic severities in the ARX gene...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798108/behavioural-abnormalities-in-novel-mouse-model-for-silver-russell-syndrome
#11
Grainne Iseult McNamara, Brittany Ann Davis, Dominic Michael Dwyer, Rosalind M John, Anthony Roger Isles
Silver Russell Syndrome (SRS) syndrome is an imprinting disorder involving low birth weight with complex genetics and diagnostics. Some rare SRS patients carry maternally inherited microduplications spanning the imprinted genes CDKN1C, PHLDA2, SLC22A18 and KCNQ1, suggesting that overexpression of one of more of these genes contributes to the SRS phenotype. While this molecular alteration is very rare, feeding difficulties are a very common feature of this condition. Given that SRS children also have very low body mass index, understanding the underpinning biology of the eating disorder is important, as well as potential co-occurring behavioural alterations...
October 24, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798107/high-levels-of-sarcospan-are-well-tolerated-and-act-as-a-sarcolemmal-stabilizer-to-address-skeletal-muscle-and-pulmonary-dysfunction-in-dmd
#12
Elizabeth M Gibbs, Jamie L Marshall, Eva Ma, Thien M Nguyen, Grace Hong, Jessica Lam, Melissa J Spencer, Rachelle H Crosbie-Watson
Duchenne muscular dystrophy (DMD) is a genetic disorder that causes progressive muscle weakness, ultimately leading to early mortality in affected teenagers and young adults. Previous work from our lab has shown that a small transmembrane protein called sarcospan (SSPN) can enhance the recruitment of adhesion complex proteins to the cell surface. When human SSPN is expressed at three-fold levels in mdx mice, this increase in adhesion complex abundance improves muscle membrane stability, preventing many of the histopathological changes associated with DMD...
October 24, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798106/dna-methylation-independent-removable-insulator-controls-chromatin-remodeling-at-the-hoxa-locus-via-retinoic-acid-signaling
#13
Ko Ishihara, Masafumi Nakamoto, Mitsuyoshi Nakao
Chromatin insulators partition the genome into functional units to control gene expression, particularly in complex chromosomal regions. The CCCTC-binding factor (CTCF) is an insulator-binding protein that functions in transcriptional regulation and higher-order chromatin formation. Variable CTCF-binding sites have been identified to be cell type-specific partly due to differential DNA methylation. Here, we show that DNA methylation-independent removable CTCF insulator is responsible for retinoic acid (RA)-mediated higher-order chromatin remodeling in the human HOXA gene locus...
October 24, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798092/igf-1-gh-axis-enhances-losartan-treatment-in-lama2-related-muscular-dystrophy
#14
Anthony Accorsi, Ajay Kumar, Younghwa Rhee, Alex Miller, Mahasweta Girgenrath
As the complexities of dystrophic pathology have been elucidated over the last few years, it has become increasingly clear that primary monogenetic defects result in multiple secondary pathologies capable of autonomously driving disease progression. Consequently, single-mode therapies fail to comprehensively ameliorate all aspects of pathology. Lama2-related muscular dystrophy (MDC1A) is a devastating congenital muscular dystrophy caused by mutations in the LAMA2 gene that results in multi-faceted secondary pathologies that include inflammation, fibrosis, apoptosis, and necrosis leading to severe muscle weakness and minimal postnatal growth...
October 24, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798105/effects-of-the-bowen-conradi-syndrome-mutation-in-emg1-on-its-nuclear-import-stability-and-nucleolar-recruitment
#15
Ahmed S Warda, Bernard Freytag, Sara Haag, Katherine E Sloan, Dirk Görlich, Markus T Bohnsack
Bowen-Conradi syndrome (BCS) is a severe genetic disorder that is characterised by various developmental abnormalities, bone marrow failure and early infant death. This disease is caused by a single mutation leading to the aspartate 86 to glycine (D86G) exchange in the essential nucleolar RNA methyltransferase EMG1. EMG1 is required for the synthesis of the small ribosomal subunit and is involved in modification of the 18S ribosomal RNA. Here, we identify the pre-ribosomal factors NOP14, NOC4L and UTP14A as members of a nucleolar subcomplex that contains EMG1 and is required for its recruitment to nucleoli...
October 23, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798104/uv-b-induced-cutaneous-inflammation-and-prospects-for-antioxidant-treatment-in-kindler-syndrome
#16
Kristin Maier, Yinghong He, Ute Wölfle, Philipp R Esser, Tilman Brummer, Christoph Schempp, Leena Bruckner-Tuderman, Cristina Has
Kindler syndrome (KS), a rare, autosomal recessive disorder comprises mechanical skin fragility and photosensitivity, which manifest early in life. The progression of the disorder is irreversible and results in tissue damage in form of cutaneous and mucosal atrophy and scarring and epithelial cancers. Here we unravel molecular mechanisms of increased UV-B sensitivity of keratinocytes derived from KS patients. We show that the pro-inflammatory cytokines, IL-1ß, IL-6 and TNF-α, are upregulated in KS skin and in UV-B irradiated KS keratinocytes...
October 23, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798099/structural-analysis-of-x-linked-retinoschisis-mutations-reveals-distinct-classes-which-differentially-effect-retinoschisin-function
#17
Ewan P Ramsay, Richard F Collins, Thomas W Owens, C Alistair Siebert, Richard P O Jones, Tao Wang, Alan M Roseman, Clair Baldock
Retinoschisin, an octameric retinal-specific protein, is essential for retinal architecture with mutations causing X-linked retinoschisis (XLRS), a monogenic form of macular degeneration. Most XLRS-associated mutations cause intracellular retention, however a subset are secreted as octamers and the cause of their pathology is ill-defined. Therefore, here we investigated the solution structure of the retinoschisin monomer and the impact of two XLRS-causing mutants using a combinatorial approach of biophysics and cryo-EM...
October 23, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798098/impaired-protein-stability-and-nuclear-localization-of-nobox-variants-associated-with-premature-ovarian-insufficiency
#18
Ilaria Ferrari, Justine Bouilly, Isabelle Beau, Fabiana Guizzardi, Alberto Ferlin, Marzia Pollazzon, Mariacarolina Salerno, Nadine Binart, Luca Persani, Raffaella Rossetti
Premature Ovarian Insufficiency (POI) is a clinical syndrome defined by a loss of ovarian activity before the age of 40. Its pathogenesis is still largely unknown, but increasing evidences support a genetic basis in most cases. Among these, heterozygous mutations in NOBOX, a homeobox gene encoding a transcription factor expressed specifically by oocyte and granulosa cells within the ovary, have been reported in ~ 6 % of women with sporadic POI. The pivotal role of NOBOX in early folliculogenesis is supported by findings in knock-out mice...
October 23, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798095/myeloid-cells-are-capable-of-synthesizing-aldosterone-to-exacerbate-damage-in-muscular-dystrophy
#19
Jessica A Chadwick, Sarah A Swager, Jeovanna Lowe, Steven S Welc, James G Tidball, Celso E Gomez-Sanchez, Elise P Gomez-Sanchez, Jill A Rafael-Fortney
FDA-approved mineralocorticoid receptor (MR) antagonists are used to treat heart failure. We have recently demonstrated efficacy of MR antagonists for skeletal muscles in addition to heart in Duchenne muscular dystrophy mouse models and that mineralocorticoid receptors are present and functional in skeletal muscles. The goal of this study was to elucidate the underlying mechanisms of MR antagonist efficacy on dystrophic skeletal muscles. We demonstrate for the first time that infiltrating myeloid cells clustered in damaged areas of dystrophic skeletal muscles have the capacity to produce the natural ligand of MR, aldosterone, which in excess is known to exacerbate tissue damage...
October 23, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27798094/modelling-c9orf72-dipeptide-repeat-proteins-of-a-physiologically-relevant-size
#20
Janis Bennion Callister, Sarah Ryan, Joan Sim, Sara Rollinson, Stuart M Pickering-Brown
C9orf72 expansions are the most common genetic cause of FTLD and MND identified to date. Although being intronic, the expansion is translated into five different dipeptide repeat proteins (DPRs) that accumulate within patients' neurons. Attempts have been made to model DPRs in cell and animals. However, the majority of these use DPRs repeat numbers much shorter than those observed in patients. To address this we have generated a selection of DPR expression constructs with repeat numbers in excess of 1000 repeats, matching what is seen in patients...
October 23, 2016: Human Molecular Genetics
journal
journal
31056
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"